|
1
|
Li H, Wang H, Li Z, Kelley N, Ouyang M, Wu JW, Meng F, Ou WB. Anti-proliferative and anti-invasive effects of exogenous thermostable MnSOD in gastric cancer associated with p53 and ZEB1 expression. J Cancer 2025; 16:2062-2074. [PMID: 40092690 PMCID: PMC11905419 DOI: 10.7150/jca.102600] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Accepted: 02/15/2025] [Indexed: 03/19/2025] Open
Abstract
The incidence of gastric cancer accounts for the first malignant tumor of the digestive tract. Although some progress in gastric cancer treatments has been made, uncontrollable drug resistance makes the development of new targeted drugs and treatment options increasingly urgent. The biological function of endogenous manganese superoxide dismutase (MnSOD) has been widely studied, whereas the anti-tumor growth effects of exogenous thermostable MnSOD in gastric cancer, an oral recombinant protein drug, are still unclear. Here, compared to normal gastric epithelial cell line and enzymatic dead mutant MnSOD H29A, we show that exogenous MnSOD treatment resulted in reduction of cell viability, colony formation, migration, and invasiveness; inhibition of SGC7901 xenograft growth; induction of apoptosis and arrest of G2-phase population in gastric cancer by an enzymatic activity-dependent manner; upregulation of p53, p21, and E-cadherin; and downregulation of cyclin D1 and N-cadherin. Unexpectedly, MnSOD treatment induced zinc finger E-box homeobox 1 (ZEB1) expression in SGC7901 gastric cancer cells, which was associated with a poor five-year survival rate and poor prognosis in gastric cancer patients. However, anti-proliferative effects of exogenous MnSOD were enhanced in SGC7901 after ZEB1 knockdown, whereas attenuated in BGC823 after ZEB1 restoration. These findings indicate that the exogenous thermostable MnSOD inhibited gastric cancer growth associated with p53 and ZEB1 expression levels and highlight that the exogenous thermostable MnSOD as an oral drug warrants evaluation as a novel therapeutic strategy in gastric cancer.
Collapse
Affiliation(s)
- Hailong Li
- Institute of Molecular Enzymology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, China
| | - Hao Wang
- Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Zong Li
- Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| | - Natalia Kelley
- Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | | | - Jia-Wei Wu
- Institute of Molecular Enzymology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, China
| | - Fanguo Meng
- Institute of Molecular Enzymology, School of Biology & Basic Medical Sciences, Suzhou Medical College of Soochow University, Suzhou, China
| | - Wen-Bin Ou
- Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and Biomedicine, College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou, China
| |
Collapse
|
|
2
|
Kulkarni A, Muralidharan C, May SC, Tersey SA, Mirmira RG. Inside the β Cell: Molecular Stress Response Pathways in Diabetes Pathogenesis. Endocrinology 2022; 164:bqac184. [PMID: 36317483 PMCID: PMC9667558 DOI: 10.1210/endocr/bqac184] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/06/2022] [Indexed: 11/05/2022]
Abstract
The pathogeneses of the 2 major forms of diabetes, type 1 and type 2, differ with respect to their major molecular insults (loss of immune tolerance and onset of tissue insulin resistance, respectively). However, evidence suggests that dysfunction and/or death of insulin-producing β-cells is common to virtually all forms of diabetes. Although the mechanisms underlying β-cell dysfunction remain incompletely characterized, recent years have witnessed major advances in our understanding of the molecular pathways that contribute to the demise of the β-cell. Cellular and environmental factors contribute to β-cell dysfunction/loss through the activation of molecular pathways that exacerbate endoplasmic reticulum stress, the integrated stress response, oxidative stress, and impaired autophagy. Whereas many of these stress responsive pathways are interconnected, their individual contributions to glucose homeostasis and β-cell health have been elucidated through the development and interrogation of animal models. In these studies, genetic models and pharmacological compounds have enabled the identification of genes and proteins specifically involved in β-cell dysfunction during diabetes pathogenesis. Here, we review the critical stress response pathways that are activated in β cells in the context of the animal models.
Collapse
Affiliation(s)
- Abhishek Kulkarni
- Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
| | - Charanya Muralidharan
- Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
| | - Sarah C May
- Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
| | - Sarah A Tersey
- Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
| | - Raghavendra G Mirmira
- Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, Illinois 60637, USA
| |
Collapse
|
|
3
|
Mahfoz AM, Gawish AY. Insight into the hepatoprotective, hypolipidemic, and antidiabetic impacts of aliskiren in streptozotocin-induced diabetic liver disease in mice. Diabetol Metab Syndr 2022; 14:163. [PMID: 36316746 PMCID: PMC9620647 DOI: 10.1186/s13098-022-00935-5] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2022] [Accepted: 10/19/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Diabetic hepatopathy is a serious complication of poorly controlled diabetes mellitus. An efficient antidiabetic drug which keeps normal liver tissues is not available. The renin-angiotensin system has been reported to be involved in both diabetic state and liver function. Aliskiren is a direct renin inhibitor and a recently antihypertensive drug with poly-pharmacological properties. The aim of the current study is to explore the possible hepatoprotective effects and mechanisms of action of aliskiren against streptozotocin (STZ) induced liver toxicity. METHODS Mice were distributed to 3 groups; first: the normal control group, second: the diabetic control group, third: the diabetic group which received aliskiren (25 mg/kg; oral) for 4 weeks. At the end of the treatment period, plasma glucose, insulin, lipid profile, oxidative stress, and liver function tests were evaluated spectrophotometrically. ELISA technique was used to measure the expression levels of TNF-α and adiponectin. Furthermore, a Histopathological examination of liver samples was done. RESULTS It was shown that aliskiren treatment ameliorated the STZ-induced oxidative stress and elevated inflammatory biomarkers, hypercholesterolemia, serum aminotransferases and alkaline phosphatase levels in diabetic mice. In addition, hepatocellular necrosis, and fibrosis were improved by aliskiren treatment. CONCLUSION aliskiren protects against the liver damage caused by STZ-induced diabetes. This can be explained by its ability to block angiotensin-II, and its anti-diabetic, hypocholesterolemic, antioxidant and anti-inflammatory effects. Aliskiren could be a novel therapeutic strategy to prevent liver diseases associated with hypertension and diabetes mellitus.
Collapse
Affiliation(s)
- Amal M Mahfoz
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt.
| | - Aya Y Gawish
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt
| |
Collapse
|
|
4
|
Guan Y, Sun H, Chen H, Li P, Shan Y, Li X. Physicochemical characterization and the hypoglycemia effects of polysaccharide isolated from Passiflora edulis Sims peel. Food Funct 2021; 12:4221-4230. [PMID: 33876796 DOI: 10.1039/d0fo02965c] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
One polysaccharide, designated as WPEP-A, was isolated from Passiflora edulis Sims peel and its hypoglycemic effects on diabetic db/db mice were evaluated. Physicochemical characterization showed that WPEP-A was composed of galactose, glucose, xylose, rhamnose, galacturonic acid and glucuronic acid with a molecular weight of 9.51 × 104 Da. We observed an inhibition in weight gain and blood glucose levels. Glucose tolerance and insulin tolerance improved after the administration of WPEP-A. In addition, our data showed increased antioxidant enzyme activities. Furthermore, the levels of serum insulin and triglyceride decreased with the recovery of liver damage. Meanwhile, positive changes in short chain fatty acid content were observed, and the mRNA levels of glucagon-like peptide 1 receptor, glucagon and prohormone convertase 3 were up-regulated in the intestinal tract. In summary, our results showed that WPEP-A had hypoglycemic activity and improved intestinal function in diabetic mice, which may contribute to the attenuation of the hypoglycemia effects.
Collapse
Affiliation(s)
- Yuan Guan
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Hefei Sun
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Huiying Chen
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Peijun Li
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| | - Yang Shan
- Hunan Agricultural Product Processing Institute, Hunan Academy of Agricultural Sciences, Changsha, Hunan 410125, China
| | - Xia Li
- College of Chemistry and Bioengineering, Guilin University of Technology, Guilin, Guangxi 541006, China.
| |
Collapse
|
|
5
|
Islam MN, Rauf A, Fahad FI, Emran TB, Mitra S, Olatunde A, Shariati MA, Rebezov M, Rengasamy KRR, Mubarak MS. Superoxide dismutase: an updated review on its health benefits and industrial applications. Crit Rev Food Sci Nutr 2021; 62:7282-7300. [PMID: 33905274 DOI: 10.1080/10408398.2021.1913400] [Citation(s) in RCA: 106] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Many short-lived and highly reactive oxygen species, such as superoxide anion (O2-) and hydrogen peroxide (H2O2), are toxic or can create oxidative stress in cells, a response involved in the pathogenesis of numerous diseases depending on their concentration, location, and cellular conditions. Superoxide dismutase (SOD) activities as an endogenous and exogenous cell defense mechanism include the potential use in treating various diseases, improving the potential use in treating various diseases, and improving food-stuffs preparation dietary supplements human nutrition. Published work indicates that SOD regulates oxidative stress, lipid metabolism, inflammation, and oxidation in cells. It can prevent lipid peroxidation, the oxidation of low-density lipoprotein in macrophages, lipid droplets' formation, and the adhesion of inflammatory cells into endothelial monolayers. It also expresses antioxidant effects in numerous cancer-related processes. Additionally, different forms of SOD may also augment food processing and pharmaceutical applications, exhibit anticancer, antioxidant, and anti-inflammatory effects, and prevent arterial problems by protecting the proliferation of vascular smooth muscle cells. Many investigations in this review have reported the therapeutic ability and physiological importance of SOD. Because of their antioxidative effects, SODs are of great potential in the medicinal, cosmetic, food, farming and chemical industries. This review discusses the findings of human and animal studies that support the advantages of SOD enzyme regulations to reduce the formation of oxidative stress in various ways.
Collapse
Affiliation(s)
- Mohammad Nazmul Islam
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Swabi, Pakistan
| | - Fowzul Islam Fahad
- Department of Pharmacy, International Islamic University Chittagong, Chittagong, Bangladesh
| | - Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
| | - Saikat Mitra
- Faculty of Pharmacy, Department of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Ahmed Olatunde
- Department of Biochemistry, Abubakar Tafawa Balewa University, Bauchi, Nigeria
| | - Mohammad Ali Shariati
- K.G. Razumovsky Moscow State University of Technologies and Management (the First Cossack University), Moscow, Russian Federation
| | - Maksim Rebezov
- V.M. Gorbatov Federal Research Center for Food Systems of Russian Academy of Sciences, Moscow, Russian Federation
- Prokhorov General Physics Institute of the Russian Academy of Science, Moscow, Russian Federation
| | - Kannan R R Rengasamy
- Green Biotechnologies Research Centre of Excellence, University of Limpopo, Polokwane, South Africa
| | | |
Collapse
|
|
6
|
Dong X, Wang W, Li S, Han H, Lv P, Yang C. Thermoacidophilic Alicyclobacillus Superoxide Dismutase: Good Candidate as Additives in Food and Medicine. Front Microbiol 2021; 12:577001. [PMID: 33815303 PMCID: PMC8014015 DOI: 10.3389/fmicb.2021.577001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2020] [Accepted: 02/26/2021] [Indexed: 11/30/2022] Open
Abstract
Thermoacidophilic Alicyclobacillus strains attract great interests as the resource of thermostable or acidic enzymes. In this study, a putative gene encoding superoxide dismutase (AaSOD) was identified in a thermoacidophilic Alicyclobacillus strain. With a 16-fold activity observed, the AaSOD activity expressing in the medium of manganese enrichment was much higher than that in the iron medium. In addition, the purified AaSOD can be reconstituted exclusively with either Fe2+ or Mn2+, with its Mn-bound protein showing 25-fold activity than that of Fe-bound form. The optimal temperature for AaSOD reaction was 35°C, and was highly stable at any certain temperature up to 80°C. Of particular interest, the enzyme is found to be very stable across a wide pH range spanning from 2.0 to 10.0, which confers its robust stability in the acidic stomach environment and implies striking potentials as food additive and for medical use.
Collapse
Affiliation(s)
- Xueqian Dong
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, China.,Shandong Food Ferment Industry Research & Design Institute, QiLu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Wei Wang
- Shandong Food Ferment Industry Research & Design Institute, QiLu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Shannan Li
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, China
| | - Hongyu Han
- Shandong Food Ferment Industry Research & Design Institute, QiLu University of Technology (Shandong Academy of Sciences), Jinan, China
| | - Peiwen Lv
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, China
| | - Chunyu Yang
- State Key Laboratory of Microbial Technology, Institute of Microbial Technology, Shandong University, Qingdao, China
| |
Collapse
|
|
7
|
Naderi R, Pourheydar B, Ghiasi R, Shafiei F. Modulatory effect of tropisetron in the liver of streptozotocin-induced diabetes in rats: biochemical and histological evidence. Horm Mol Biol Clin Investig 2020; 41:hmbci-2020-0002. [PMID: 32364517 DOI: 10.1515/hmbci-2020-0002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 04/04/2020] [Indexed: 12/19/2022]
Abstract
Objectives There is an association between diabetes and liver disorders. Oxidative stress plays a crucial role in the pathology of hepatic abnormalities in diabetes. In this study, the effect of Tropisetron on the oxidative damage and histological alterations in the liver of type 1 diabetes mellitus (DM) were evaluated. Methods Thiry-five male Wistar rats were randomly divided into five experimental groups (n = 7): control (C), tropisetron (T), diabetes (D), diabetes + tropisetron (D + T) and diabetes + glibenclamide (D + G). A single injection of streptozotocin (STZ, 50 mg/kg; i.p) was used to induce diabetes. Tropisetron (3 mg/kg; i.p), as a 5-HT3 receptor antagonist and glibenclamide (1 mg/kg; i.p), as a positive control were given once daily for 2 weeks. Finally, animals were euthanized and liver samples were obtained for histopathological examination and biochemical measurements including malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) levels. Results There is a significant increase in MDA (p < 0.001) level and a significant decrease (p < 0.001) in SOD and GPx contents in diabetic animals. Tropisetron attenuated MDA levels (p < 0.001) and enhanced SOD (p < 0.05) and GPx (p < 0.01) activities accompanied by histopathological improvement in the diabetes liver. Similar results were achieved in the rats treated with the standard drug, namely: glibenclamide. Conclusions Our findings indicate that tropisetron mitigates liver damage in the diabetes rats in part by attenuation of oxidative stress.
Collapse
Affiliation(s)
- Roya Naderi
- Nephrology and Kidney Transplant Research Center, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.,Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
| | - Bagher Pourheydar
- Neurophysiology Research Center, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran.,Department of Anatomical Sciences, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
| | - Rafigheh Ghiasi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.,Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran
| | - Fardin Shafiei
- Department of Physiology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Islamic Republic of Iran
| |
Collapse
|
|
8
|
Stephenie S, Chang YP, Gnanasekaran A, Esa NM, Gnanaraj C. An insight on superoxide dismutase (SOD) from plants for mammalian health enhancement. J Funct Foods 2020. [DOI: 10.1016/j.jff.2020.103917] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
|
|
9
|
Eftekhari A, Hasanzadeh A, Khalilov R, Hosainzadegan H, Ahmadian E, Eghbal MA. Hepatoprotective role of berberine against paraquat-induced liver toxicity in rat. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:4969-4975. [PMID: 31845254 DOI: 10.1007/s11356-019-07232-1] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 12/02/2019] [Indexed: 06/10/2023]
Abstract
Paraquat (PQ) is a herbicide agent commonly used in agricultural applications. Hepatotoxicity is among clinical complications associated with PQ intoxication. Oxidative stress and its subsequent events are major mechanisms identified in PQ-induced liver toxicity. Berberine (BBR) is a natural antioxidant widely investigated for its hepatoprotective effects. The present study designed to evaluate the potential cytoprotective properties of BBR against PQ-induced cytotoxicity in primary cultured rat hepatocytes and in vivo test of liver function enzymes. Cellular and biochemical parameters including lactate dehydrogenase (LDH), cell viability, ROS formation, glutathione (GSH) content, and mitochondrial membrane potential in the PQ-treated hepatocytes were measured, and the mentioned markers were evaluated in the presence of BBR. BBR treatment caused significant decrease in PQ-induced cell death, ROS formation, and LDH release. On the other hand, it was found that BBR inhibits cellular glutathione depletion in PQ-treated hepatocytes. Also, BBR treatment significantly diminished PQ-induced the liver function enzyme elevation. These data mention the potential hepatoprotective effect of BBR with therapeutic capability against PQ-induced liver damage.
Collapse
Affiliation(s)
| | | | - Rovshan Khalilov
- Russian Institute for Advanced Study, Moscow State Pedagogical University, 1/1, Malaya Pirogovskaya St, Moscow, Russian Federation, 119991
- Department of Biophysics and Molecular Biology, Baku State University, Baku, Azerbaijan
- Joint Ukraine-Azerbaijan International Research and Education Center of Nanobiotechnology and Functional Nanosystems, Drohobych, Ukraine & Baku, Azerbaijan
| | | | - Elham Ahmadian
- Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
- Students' Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Mohammad Ali Eghbal
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
|
10
|
Chen Z, Wang J, Fan Z, Qiu J, Rumbani M, Yang X, Zhang H, Wang Z. Effects of polysaccharide from the fruiting bodies of Auricularia auricular on glucose metabolism in 60Co-γ-radiated mice. Int J Biol Macromol 2019; 135:887-897. [DOI: 10.1016/j.ijbiomac.2019.05.136] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/12/2019] [Accepted: 05/21/2019] [Indexed: 11/25/2022]
|
|
11
|
Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive cells and tissues: importance to cell metabolism, function, and dysfunction. Am J Physiol Cell Physiol 2019; 317:C420-C433. [PMID: 31216193 DOI: 10.1152/ajpcell.00141.2019] [Citation(s) in RCA: 125] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
It is now accepted that nutrient abundance in the blood, especially glucose, leads to the generation of reactive oxygen species (ROS), ultimately leading to increased oxidative stress in a variety of tissues. In the absence of an appropriate compensatory response from antioxidant mechanisms, the cell, or indeed the tissue, becomes overwhelmed by oxidative stress, leading to the activation of intracellular stress-associated pathways. Activation of the same or similar pathways also appears to play a role in mediating insulin resistance, impaired insulin secretion, and late diabetic complications. The ability of antioxidants to protect against the oxidative stress induced by hyperglycemia and elevated free fatty acid (FFA) levels in vitro suggests a causative role of oxidative stress in mediating the latter clinical conditions. In this review, we describe common biochemical processes associated with oxidative stress driven by hyperglycemia and/or elevated FFA and the resulting clinical outcomes: β-cell dysfunction and peripheral tissue insulin resistance.
Collapse
Affiliation(s)
- Philip Newsholme
- School of Pharmacy and Biomedical Sciences, and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - Kevin N Keane
- School of Pharmacy and Biomedical Sciences, and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - Rodrigo Carlessi
- School of Pharmacy and Biomedical Sciences, and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
| | - Vinicius Cruzat
- Faculty of Health, Torrens University Australia, Melbourne, Victoria, Australia
| |
Collapse
|
|
12
|
Zhao JG, Wang HY, Wei ZG, Zhang YQ. Therapeutic effects of ethanolic extract from the green cocoon shell of silkworm Bombyx mori on type 2 diabetic mice and its hypoglycaemic mechanism. Toxicol Res (Camb) 2019; 8:407-420. [PMID: 31160974 DOI: 10.1039/c8tx00294k] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 01/04/2019] [Indexed: 01/13/2023] Open
Abstract
Diabetes mellitus is a clinically complex disease characterized by hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism. The aim of this study was to determine the therapeutic effect of ethanolic extract (EE) from the green cocoon sericin layer of silkworm Bombyx mori on mice with type 2 diabetes mellitus (T2DM) and its hypoglycaemic mechanisms. The results showed that oral EE for 7 weeks had significant ameliorative effects on all the biochemical parameters studied in vivo. The levels of oral glucose tolerance and insulin tolerance were significantly improved. The hypoglycaemic rate in the 350 mg kg-1 high dosage group was 39.38%. The levels of nuclear factor kappa B (NFκB), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) in the high dosage EE-treated group were significantly reduced, while activities of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were obviously increased. The islet area and the number of insulin-positive beta cells increased significantly in the high dose group. Furthermore, expression levels of insulin receptor (IR), insulin receptor substrate (IRS), phosphatidylinositide 3-kinase (PI3K), p-Akt and phospho-glycogen synthase kinase-3β (p-GSK3β) involved in insulin signalling were increased. Adenosine 5'-monophosphate-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4) also were activated to regulate glucose metabolism in EE-treated groups. The levels of glucose 6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) decreased, while the glucokinase (GK) level increased to promote glycolysis. The results clearly indicated that oral EE, especially at a high dose, could improve the glucose metabolism of T2DM by reducing inflammatory reactions, enhancing the antioxidant capacity and insulin sensitivity, and regulating the balance between glycolysis and gluconeogenesis, which means that EE has potential ameliorative effects on T2DM mice.
Collapse
Affiliation(s)
- Jin-Ge Zhao
- Silk Biotechnology Laboratory , School of Biology and Basic Medical Sciences , Soochow University , China .
| | - Hai-Yan Wang
- Silk Biotechnology Laboratory , School of Biology and Basic Medical Sciences , Soochow University , China .
| | - Zheng-Guo Wei
- Silk Biotechnology Laboratory , School of Biology and Basic Medical Sciences , Soochow University , China .
| | - Yu-Qing Zhang
- Silk Biotechnology Laboratory , School of Biology and Basic Medical Sciences , Soochow University , China .
| |
Collapse
|
|
13
|
Chiş IC, Baltaru D, Dumitrovici A, Coseriu A, Radu BC, Moldovan R, Mureşan A. Protective effects of quercetin from oxidative/nitrosative stress under intermittent hypobaric hypoxia exposure in the rat's heart. Physiol Int 2019; 105:233-246. [PMID: 30282485 DOI: 10.1556/2060.105.2018.3.23] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
BACKGROUND Exposure to high altitude in hypobaric hypoxia (HH) is considered to be a physiological oxidative/nitrosative stress. Quercetin (Que) is an effective antioxidant and free radical scavenger against oxidative/nitrosative stress. AIMS The aim of this study was to investigate the cardioprotective effects of Que in animals exposed to intermittent HH (IHH) and therefore exposed to oxidative/nitrosative stress. MATERIALS AND METHODS Wistar albino male rats were exposed to short-term (2 days) or long-term (4 weeks; 5 days/week) IHH in a hypobaric chamber (5,500 m, 8 h/day, 380 mmHg, 12% O2, and 88% N2). Half of the animals received natural antioxidant Que (body weight: 30 mg/kg) daily before each IHH exposure and the remaining rats received vehicle (carboxymethylcellulose solution). Control rats were kept under normobaric normoxia (Nx) and treated in a corresponding manner. One day after the last exposure to IHH, we measured the cardiac hypoxia-induced oxidative/nitrosative stress biomarkers: the malondialdehyde (MDA) level and protein carbonyl (PC) content, the activity of some antioxidant enzymes [superoxide dismutase (SOD) and catalase (CAT)], the nitrite plus nitrate (NOx) production, and the inducible nitric oxide synthase (iNOS) protein expression. RESULTS Heart tissue MDA and PC levels, NOx level, and iNOS expression of IHH-exposed rats had increased, and SOD and CAT activities had decreased compared with those of the Nx-exposed rats (control groups). MDA, CP, NOx, and iNOS levels had decreased in Que-treated IHH-exposed rats compared with IHH-exposed rats (control groups). However, Que administration increased SOD and CAT activities of the heart tissue in the IHH-exposed rats. CONCLUSION HH exposure increases oxidative/nitrosative stress in heart tissue and Que is an effective cardioprotective agent, which further supports the oxidative cardiac dysfunction induced by hypoxia.
Collapse
Affiliation(s)
- I C Chiş
- 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania
| | - D Baltaru
- 2 Department of Internal Medicine, "Constantin Papilian" Military Emergency Hospital , Cluj-Napoca, Romania
| | - A Dumitrovici
- 3 Department of Medical Oncology, "I. Chiricuta" Oncologic Institute , Cluj-Napoca, Romania
| | - A Coseriu
- 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania
| | - B C Radu
- 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania
| | - R Moldovan
- 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania
| | - A Mureşan
- 1 Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy , Cluj-Napoca, Romania
| |
Collapse
|
|
14
|
Chen C, You LJ, Huang Q, Fu X, Zhang B, Liu RH, Li C. Modulation of gut microbiota by mulberry fruit polysaccharide treatment of obese diabetic db/db mice. Food Funct 2018; 9:3732-3742. [PMID: 29995048 DOI: 10.1039/c7fo01346a] [Citation(s) in RCA: 130] [Impact Index Per Article: 18.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Increasing evidence indicates that gut microbiota is an important factor in mediating the development of metabolic disorders, especially type 2 diabetes. Herein, we investigated the protective effects of polysaccharides from mulberry fruit on diabetic db/db mice. We observed an inhibition in the body weight increase, a decrease in the blood glucose levels, and an improvement in glucose tolerance. Furthermore, our data showed increased enzymatic activities as evidenced by parameters such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). In addition, high density lipoprotein cholesterol (HDL-C) increased, while total cholesterol (TC), triacylglycerol (TG), low density lipoprotein cholesterol (LDL-C), lipid peroxide content malonaldehyde (MDA), and free fatty acid (FFA) levels decreased, accompanied by the recovery from damage to the liver, kidneys and pancreas. Meanwhile, metformin and polysaccharide similarly shifted the abundance of the main gut microbiota, Bacteroidetes and Firmicutes, in diabetic mice toward levels observed in healthy mice. Especially at the genus level, the enrichment of some key bacteria like Bacteroidales, Lactobacillus, Allobaculum, Bacteroides, and Akkermansia was observed. Taken together, our findings suggest that polysaccharides from the mulberry fruit modulate gut microbiota, including enriching functional bacteria and reducing microbial diversity, which may contribute to their antidiabetic effects.
Collapse
Affiliation(s)
- Chun Chen
- School of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China.
| | | | | | | | | | | | | |
Collapse
|
|
15
|
Characterization and Attenuation of Streptozotocin-Induced Diabetic Organ Damage by Polysaccharides from Spent Mushroom Substrate (Pleurotus eryngii). OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:4285161. [PMID: 30364025 PMCID: PMC6186375 DOI: 10.1155/2018/4285161] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 07/19/2018] [Indexed: 01/28/2023]
Abstract
The aim of this work was to characterize spent mushroom substrate polysaccharides (MSP) from Pleurotus eryngii and their antioxidant and organ protective effects in streptozotocin- (STZ-) induced diabetic mice. The enzymatic-, acidic-, and alkalic- (En-, Ac-, and Al-) MSP were extracted from P. eryngii with snailase (4%), hydrochloric acid (1 mol/l), and sodium hydroxide (1 mol/l), respectively. The characterizations were evaluated by spectral analysis. In animal experiments, the enzymatic activities, lipid peroxide contents, and serum lipid parameters were measured, and histological observations of the liver, kidney, pancreas, and heart were conducted. The results demonstrated that treatment with En-, Ac-, and Al-MSP increased the organ enzymatic activities, decreased the organ lipid peroxide contents, mitigated the serum biochemistry values, and ameliorated the histopathology of diabetic mice, indicating that En-, Ac-, and Al-MSP could potentially be used as functional foods for the prevention of diabetes.
Collapse
|
|
16
|
Younus H. Therapeutic potentials of superoxide dismutase. Int J Health Sci (Qassim) 2018; 12:88-93. [PMID: 29896077 PMCID: PMC5969776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
Abstract
Superoxide dismutases (SODs) constitute a very important antioxidant defense against oxidative stress in the body. The enzyme acts as a good therapeutic agent against reactive oxygen species-mediated diseases. The present review describes the therapeutic effects of SOD in various physiological and pathological conditions such as cancer, inflammatory diseases, cystic fibrosis, ischemia, aging, rheumatoid arthritis, neurodegenerative diseases, and diabetes. However, the enzyme has certain limitations in clinical applications. Therefore, SOD conjugates and mimetics have been developed to increase its therapeutic efficiency. Here, an overview is provided of some in vivo therapeutic effects observed with SOD.
Collapse
Affiliation(s)
- H. Younus
- Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh, Uttar Pradesh, India,Address for correspondence: H. Younus, Interdisciplinary Biotechnology Unit, Aligarh Muslim University, Aligarh - 202002, Uttar Pradesh, India. Tel.: +91 571 2720 388. Fax: +91 571 272 1776. E-mail:
| |
Collapse
|
|
17
|
Zhang C, Li J, Hu C, Wang J, Zhang J, Ren Z, Song X, Jia L. Antihyperglycaemic and organic protective effects on pancreas, liver and kidney by polysaccharides from Hericium erinaceus SG-02 in streptozotocin-induced diabetic mice. Sci Rep 2017; 7:10847. [PMID: 28883631 PMCID: PMC5589823 DOI: 10.1038/s41598-017-11457-w] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 08/24/2017] [Indexed: 02/06/2023] Open
Abstract
The present work was designed to investigate the antihyperglycaemic and protective effects of two Hericium erinaceus intracellular polysaccharide (HIPS) purified fractions (HIPS1 and HIPS2) from mycelia of H. erinaceus SG-02 on pancreas, liver and kidney in streptozotocin (STZ)-induced diabetic mice. The supplementation of HIPS1 and HIPS2 significantly decreased the blood glucose (GLU) levels; suppressed the abnormal elevations of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN) and creatinine (CRE) levels in serum; improved the antioxidant enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) activities; and attenuated the pathological damage to these organs. The HIPS1 showed superior effects in antihyperglycaemia and organic protection than HIPS2 possible owing to the abundant functional groups (-NH2, -COOH and S=O) in HIPS1, indicating that H. erinaceus SG-02 could be used as a functional food and natural drug for the prevention of diabetes and its complications.
Collapse
Affiliation(s)
- Chen Zhang
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Juan Li
- Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Chunlong Hu
- College of Forestry, Shandong Agricultural University, Taian, 271018, China
| | - Jing Wang
- The Central Hospital of Taian, Taian, 271000, China
| | - Jianjun Zhang
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Zhenzhen Ren
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Xinling Song
- College of Life Science, Shandong Agricultural University, Taian, 271018, China
| | - Le Jia
- College of Life Science, Shandong Agricultural University, Taian, 271018, China.
| |
Collapse
|
|
18
|
Safakhah HA, Moradi Kor N, Bazargani A, Bandegi AR, Gholami Pourbadie H, Khoshkholgh-Sima B, Ghanbari A. Forced exercise attenuates neuropathic pain in chronic constriction injury of male rat: an investigation of oxidative stress and inflammation. J Pain Res 2017; 10:1457-1466. [PMID: 28721088 PMCID: PMC5499951 DOI: 10.2147/jpr.s135081] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND AND OBJECTIVE Initial peripheral/central nerve injuries, such as chronic constriction injury (CCI)/spinal cord injury, are often compounded by secondary mechanisms, including inflammation and oxidative stress, which may lead to chronic neuropathic pain characterized by hyperalgesia or allodynia. On the other hand, exercise as a behavioral and non-pharmacological treatment has been shown to alleviate chronic neuropathic pain. Therefore, this study was conducted to examine whether or not exercise reduces neuropathic pain through modifying oxidative stress and inflammation in chronic constriction injury of the sciatic nerve. MATERIALS AND METHODS Wistar male rats weighing 200±20 g were randomly divided into five groups (normal, sham, CCI, pre-CCI exercise, and post-CCI exercise group). Sciatic nerve of anesthetized rats was loosely ligated to induce CCI, and they were then housed in separate cages. The rats ran on treadmill at a moderate speed for 3 weeks. Mechanical allodynia and thermal hyperalgesia were determined using von Frey filament and plantar test, respectively. Tumor necrosis factor-alpha (TNF-α) assayed in the cerebrospinal fluid, malondialdehyde, and total antioxidant capacity were measured in the serum using Western blot test, thiobarbituric acid, and ferric reducing ability of plasma (FRAP), respectively. RESULTS The mechanical allodynia (P=0.024) and thermal hyperalgesia (P=0.002) in the CCI group were higher than those in the sham group. Exercise after CCI reduced (P=0.004) mechanical allodynia and thermal hyperalgesia (P=0.025) compared with the CCI group. Moreover, the level of FRAP in the CCI group was (P=0.001) lower than that in the sham group, and post-CCI exercise reversed FRAP amount toward the control level (P=0.019). The amount of malondialdehyde did not differ between groups. Level of TNF-α increased in the CCI group (P=0.0002) compared with sham group and post-CCI exercise could reverse it toward the level of control (P=0.005). CONCLUSION Post CCI-exercise but not pre CCI-exercise reduces CCI-induced neuropathic pain. One of the possible involved mechanisms is increasing the total antioxidant capacity and reducing the amount of TNF-α.
Collapse
Affiliation(s)
- Hossein Ali Safakhah
- Department of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.,Research Center of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Nasroallah Moradi Kor
- Research Center of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran.,Student Research Committee, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Atiyeh Bazargani
- Student Research Committee, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | - Ahmad Reza Bandegi
- Department of Biochemistry, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| | | | | | - Ali Ghanbari
- Research Center of Physiology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
| |
Collapse
|
|
19
|
Protective effects on liver, kidney and pancreas of enzymatic- and acidic-hydrolysis of polysaccharides by spent mushroom compost (Hypsizigus marmoreus). Sci Rep 2017; 7:43212. [PMID: 28233836 PMCID: PMC5324114 DOI: 10.1038/srep43212] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2016] [Accepted: 01/20/2017] [Indexed: 12/14/2022] Open
Abstract
The present work investigated the protective effects on liver, kidneys and pancreas of spent mushroom compost polysaccharide (SCP) and its hydrolysates (enzymatic- (ESCP) and acid-hydrolyzed SCP (ASCP)) from Hypsizigus marmoreus, in streptozotocin (STZ)-induced diabetic mice. The results showed that enzymatic (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)) and non-enzymatic activities (total antioxidant capacity (T-AOC)) were significantly increased, the lipid peroxide contents (lipid peroxide (LPO) and malonaldehyde (MDA)) were remarkably reduced, and the clinical parameters were observably mitigated in diabetic mice treated with these three polysaccharides. Furthermore, histological observations also indicated recovery. These conclusions demonstrated that both SCP and its hydrolysates ESCP and ASCP possessed potent antioxidant activities and can be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.
Collapse
|
|
20
|
Patche J, Girard D, Catan A, Boyer F, Dobi A, Planesse C, Diotel N, Guerin-Dubourg A, Baret P, Bravo SB, Paradela-Dobarro B, Álvarez E, Essop MF, Meilhac O, Bourdon E, Rondeau P. Diabetes-induced hepatic oxidative stress: a new pathogenic role for glycated albumin. Free Radic Biol Med 2017; 102:133-148. [PMID: 27890722 DOI: 10.1016/j.freeradbiomed.2016.11.026] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 10/29/2016] [Accepted: 11/14/2016] [Indexed: 01/21/2023]
Abstract
Increased oxidative stress and advanced glycation end-product (AGE) formation are major contributors to the development of type 2 diabetes. Here plasma proteins e.g. albumin can undergo glycoxidation and play a key role in diabetes onset and related pathologies. However, despite recent progress linking albumin-AGE to increased oxidative stress and downstream effects, its action in metabolic organs such as the liver remains to be elucidated. The current study therefore investigated links between oxidative perturbations and biochemical/structural modifications of plasma albumin, and subsequent downstream effects in transgenic db/db mouse livers and HepG2 cells, respectively. Our data reveal increased oxidative stress biomarkers and lipid accumulation in plasma and livers of diabetic mice, together with albumin glycoxidation. Purified mouse albumin modifications resembled those typically found in diabetic patients, i.e. degree of glycation, carbonylation, AGE levels and in terms of chemical composition. Receptor for AGE expression and reactive oxygen species production were upregulated in db/db mouse livers, together with impaired proteolytic, antioxidant and mitochondrial respiratory activities. In parallel, acute exposure of HepG2 cells to glycated albumin also elicited intracellular free radical formation. Together this study demonstrates that AGE-modified albumin can trigger damaging effects on the liver, i.e. by increasing oxidative stress, attenuating antioxidant capacity, and by impairment of hepatic proteolytic and respiratory chain enzyme activities.
Collapse
Affiliation(s)
- Jessica Patche
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Dorothée Girard
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Aurélie Catan
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Florence Boyer
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Anthony Dobi
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Cynthia Planesse
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Nicolas Diotel
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Alexis Guerin-Dubourg
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France; Centre Hospitalier Gabriel Martin, Saint-Paul de La Réunion, France
| | - Pascal Baret
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France
| | - Susana B Bravo
- Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Beatriz Paradela-Dobarro
- Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - Ezequiel Álvarez
- Proteomic Unit and Instituto de Investigación Sanitaria de Santiago de Compostela (IDIS), Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
| | - M Faadiel Essop
- Cardio-Metabolic Research Group (CMRG), Department of Physiological Sciences, Stellenbosch University, Stellenbosch, South Africa
| | - Olivier Meilhac
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France; CHU de La Réunion, Centre d'Investigation Clinique, Saint-Denis F-97400, France
| | - Emmanuel Bourdon
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
| | - Philippe Rondeau
- Université de La Réunion, INSERM, UMR 1188 Diabète athérothrombose Thérapies Réunion Océan Indien (DéTROI), plateforme CYROI, Sainte-Clotilde, France.
| |
Collapse
|
|
21
|
Shittu STT, Oyeyemi WA, Lasisi TJ, Shittu SAS, Lawal TT, Olujobi ST. Aqueous leaf extract of Ocimum gratissimum improves hematological parameters in alloxan-induced diabetic rats via its antioxidant properties. Int J Appl Basic Med Res 2016; 6:96-100. [PMID: 27127737 PMCID: PMC4830163 DOI: 10.4103/2229-516x.179016] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2015] [Accepted: 01/18/2016] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVE This study was designed to investigate the effects of Ocimum gratissimum (OG) on hematological parameters and oxidative stress in diabetic rats. MATERIALS AND METHODS Twenty-five male rats (150-200 g) were randomly grouped into five as control, normal + OG, diabetic untreated, diabetic + OG, and diabetic + glibenclamide groups. Diabetes was induced by 100 mg/kg of alloxan monohydrate in the diabetic untreated and diabetic + OG groups followed by treatment with distilled water and 400 mg/kg OG, respectively, whereas control, normal + OG, and diabetic + glibenclamide groups were treated with distilled water, 400 mg/kg OG, and 5 mg/kg glibenclamide, respectively. Body weight and fasting blood glucose level were monitored weekly. After 28 days of treatments, under anesthesia induced by 50 mg/kg sodium thiopental i.p., blood samples were obtained for hematological analysis, malondialdehyde (MDA) level determination, and superoxide dismutase (SOD) activity. Data were compared using analysis of variance and Student's t-test. RESULTS There was a significant decrease in the fasting blood glucose of the diabetic + OG animals compared to the diabetic untreated and the initial reduction in weight observed in this group was reversed at the end of the experiments. Packed cell volume, red blood cell count, and hemoglobin concentration were significantly increased (P < 0.05) in the diabetic + OG when compared with the untreated group. The MDA concentration was significantly lowered (P < 0.01) in the diabetic + OG group when compared with diabetic untreated while SOD activity was significantly reduced in the diabetic untreated group. CONCLUSION It was concluded that OG reverses anemia secondary to alloxan-induced diabetes mellitus in rats probably via its antioxidant activity.
Collapse
Affiliation(s)
| | - Wahab A Oyeyemi
- Department of Physiology, Igbinedion University, Okada, Edo State, Nigeria
| | - Taye J Lasisi
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | | | - Temitope T Lawal
- Department of Animal Science, University of Ibadan, Ibadan, Nigeria
| | - Samuel T Olujobi
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| |
Collapse
|
|
22
|
Xu BQ, Yang P, Zhang YQ. Hypoglycemic activities of lyophilized powder of Gynura divaricata by improving antioxidant potential and insulin signaling in type 2 diabetic mice. Food Nutr Res 2015; 59:29652. [PMID: 26715102 PMCID: PMC4695621 DOI: 10.3402/fnr.v59.29652] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2015] [Revised: 11/12/2015] [Accepted: 11/12/2015] [Indexed: 11/18/2022] Open
Abstract
Background Diabetes mellitus is a serious disease affecting about 5% of people worldwide. Although several studies have indicated hypoglycemic activities of Gynura divaricata (GD), the mechanisms by which GD improves the symptoms of diabetes remain unclear. Objective The aim of this study was to investigate the potential hypoglycemic effects of GD. Design The leaves and stems of GD were prepared and lyophilized into a powder, which was added to the diet of mice with type 2 diabetes induced by a high-fat diet in combination with streptozotocin for 4 weeks. During this period, fasting blood glucose (FBG) levels and body weight of mice were measured. In addition, at the end of the experiment, a series of assays was performed. Results GD administration effectively alleviates insulin resistance and induces a decrease in FBG by 59.54% in 1.2% (L) GD-treated diabetic group and 56.13% in 4.8% (H) GD-treated diabetic group after 4 weeks, respectively, relative to diabetic model mice. The antioxidant capacity was improved by increasing the activities of glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) by 64.87% and 53.42% in treatment group H, compared to diabetic model mice, while GD treatment induced a significant decrease in malondialdehyde (MDA) level by 50% in treatment group L, compared to the level in diabetic model mice. Furthermore, glucose metabolism was ameliorated by the increased glycogen synthesis in the livers of diabetic mice. In addition, we also demonstrated that the messenger RNA (mRNA) and protein expression levels of AKT, PI3K and PDK-1, which are involved in insulin signaling, were significantly increased. Conclusions Oral administration of the GD-lyophilized powder has been effectively hypoglycemic, which is done by activating insulin signaling and improving antioxidant capacity in mice with type 2 diabetes.
Collapse
Affiliation(s)
| | | | - Yu-Qing Zhang
- Silk Biotechnology Laboratory, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, China;
| |
Collapse
|
|
23
|
Zhang J, Meng G, Zhang C, Lin L, Xu N, Liu M, Cui F, Jia L. The antioxidative effects of acidic-, alkalic-, and enzymatic-extractable mycelium zinc polysaccharides by Pleurotus djamor on liver and kidney of streptozocin-induced diabetic mice. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2015; 15:440. [PMID: 26683206 PMCID: PMC4683725 DOI: 10.1186/s12906-015-0964-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2015] [Accepted: 12/09/2015] [Indexed: 01/20/2023]
Abstract
BACKGROUND Edible mushrooms, especially the genus of Pleurotus, have been well studied for their nutrition as well as non-toxic medicinal properties. Recently, much attention has been paid to the therapeutic values of mushrooms in genus of Pleurotus with diabetes mellitus (DM), which was a complex metabolic disorder that induced by increased oxidative stress and characterized by hyperglycemia. However, scare attention has been paid to polysaccharides from P. djamor. Meanwhile, zinc is an essential trace element in the human body and it participates in various pathways of metabolism. Therefore, the objective of present study was aimed to evaluate the protective effects of the three extractable mycelium zinc polysaccharides (MZPS), including acidic-MZPS (Ac-MZPS), alkalic-MZPS (Al-MZPS) and enzymatic-MZPS (En-MZPS), on the liver and kidneys in diabetic mice induced by streptozocin (STZ) aiming to better understand the possible hypoglycemic mechanisms and their health benefits. METHODS The Ac-, Al-, and En-MZPS were extracted with hydrochloric acid (1 M), sodium hydroxide (1 M) and snailase (4 %) from P. djamor zinc-enriched mycelium, respectively. The diabetic mice were induced by injection of STZ. Besides the histopathological analyses of liver and kidney, the following biochemical analysis were processed to investigate the antioxidative effects, including activities of superoxide dismutase (SOD), GSH peroxide (GSH-Px) and catalase (CAT), and contents of malondialdehyde (MDA) in liver and kidney homogenate; activities of alamine aminotransferase (ALT) and aspertate aminotransferase (AST), and levels of urea nitrogen (BUN), creatinine (CRE), total cholesterol (TC), albumin (ALB), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) in serum. RESULTS Results showed that the activities of SOD, GSH-Px and CAT were significantly increased, the MDA contents remarkably reduced, and the values of ALT, AST, BUN, CRE, TC, LDL-C and HDL-C observably mitigated in the liver, kidneys and serum of diabetic mice by these three polysaccharides treatment. Biochemical and histopathological analyses also showed that MZPS could alleviate liver and kidneys injury. CONCLUSION These results demonstrated that Ac-, Al-, and En-MZPS possessed potent antioxidant activities, and could be used as a potentially functional food for the prevention of diabetes and its complications induced by STZ.
Collapse
|
|
24
|
Cruz KJC, Oliveira ARSD, Marreiro DDN. Antioxidant role of zinc in diabetes mellitus. World J Diabetes 2015; 6:333-337. [PMID: 25789115 PMCID: PMC4360427 DOI: 10.4239/wjd.v6.i2.333] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2014] [Revised: 12/02/2014] [Accepted: 12/19/2014] [Indexed: 02/05/2023] Open
Abstract
Chronic hyperglycemia statue noticed in diabetes mellitus favors the manifestation of oxidative stress by increasing the production of reactive oxygen species and/or by reducing the antioxidant defense system activity. Zinc plays an important role in antioxidant defense in type 2 diabetic patients by notably acting as a cofactor of the superoxide dismutase enzyme, by modulating the glutathione metabolism and metallothionein expression, by competing with iron and copper in the cell membrane and by inhibiting nicotinamide adenine dinucleotide phosphate-oxidase enzyme. Zinc also improves the oxidative stress in these patients by reducing chronic hyperglycemia. It indeed promotes phosphorylation of insulin receptors by enhancing transport of glucose into cells. However, several studies reveal changes in zinc metabolism in individuals with type 2 diabetes mellitus and controversies remain regarding the effect of zinc supplementation in the improvement of oxidative stress in these patients. Faced with the serious challenge of the metabolic disorders related to oxidative stress in diabetes along with the importance of antioxidant nutrients in the control of this disease, new studies may contribute to improve our understanding of the role played by zinc against oxidative stress and its connection with type 2 diabetes mellitus prognosis. This could serve as a prelude to the development of prevention strategies and treatment of disorders associated with this chronic disease.
Collapse
|
|
25
|
Ren C, Zhang Y, Cui W, Lu G, Wang Y, Gao H, Huang L, Mu Z. A polysaccharide extract of mulberry leaf ameliorates hepatic glucose metabolism and insulin signaling in rats with type 2 diabetes induced by high fat-diet and streptozotocin. Int J Biol Macromol 2015; 72:951-9. [DOI: 10.1016/j.ijbiomac.2014.09.060] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2014] [Revised: 09/18/2014] [Accepted: 09/26/2014] [Indexed: 01/08/2023]
|
|
26
|
Effect of Salmonella typhimurium infection on rat's cell oxidation and in vivo antioxidant activity of Vitellaria paradoxa and Ludwigia abyssinica aqueous extract. ASIAN PACIFIC JOURNAL OF TROPICAL DISEASE 2015. [DOI: 10.1016/s2222-1808(14)60624-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
|
|
27
|
Dey A, Lakshmanan J. The role of antioxidants and other agents in alleviating hyperglycemia mediated oxidative stress and injury in liver. Food Funct 2014; 4:1148-84. [PMID: 23760593 DOI: 10.1039/c3fo30317a] [Citation(s) in RCA: 88] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
Several antioxidants and agents having similar antioxidant effects are known to exert beneficial effects in ameliorating the injurious effects of hyperglycemia on liver in different diabetic in vitro and in vivo models. The review deals with some of the agents which have been shown to exert protective effects on liver against hyperglycemic insult and the various mechanisms involved. The different classes of agents which protect the diabetic liver or decrease the severity of hyperglycemia mediated injury include flavonoids, catechins, and other polyphenolic compounds, curcumin and its derivatives, certain vitamins, hormones and drugs, trace elements, prototypical antioxidants and amino acids. Some of the pronounced changes mediated by the antioxidants in liver exposed to hyperglycemia include decreased oxidative stress, and alterations in carbohydrate and lipid metabolism. Other mechanisms through which the agents ameliorate hyperglycemia mediated liver injury include decrease in oxidative DNA and protein damage, restoration of mitochondrial structural and functional integrity, decrease in inflammation and improved insulin signaling. Thus, antioxidants may prove to be an important mode of defense in maintaining normal hepatic functions in diabetes.
Collapse
Affiliation(s)
- Aparajita Dey
- Life Science Division, AU-KBC Research Centre, MIT Campus of Anna University, Chromepet, Chennai 600044, India.
| | | |
Collapse
|
|
28
|
Zhao HD, Sun MN, Li MD, Li FL, Li H. Dishevelled-1 (Dvl-1) protein: a potential participant of oxidative stress induced by selenium deficiency. Biol Trace Elem Res 2014; 157:45-50. [PMID: 24234591 DOI: 10.1007/s12011-013-9859-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2013] [Accepted: 10/31/2013] [Indexed: 12/18/2022]
Abstract
Oxidative stress induced by selenium deficiency has been shown to be associated with cardiovascular diseases. Nevertheless, the mechanism associated with oxidative stress induced by selenium deficiency is poorly understood. In the present study, 36 weaning C57BL/6 mice were randomly divided into 4 groups as follows: control (n =9), 4-week selenium deficiency (n =9), 8-week selenium deficiency (n = 9), and 12-week selenium deficiency (n =9). The levels of myocardial glutathione peroxidase (GPx), superoxide dismutase (SOD), and malondialdehyde (MDA) were determined by Western blotting or commercial kits. Real-time PCR was performed to detect the mRNA expression of dishevelled-1 (Dvl-1) protein. Western blotting was conducted to evaluate the protein expression levels of Dvl-1 and β-catenin. Our results demonstrated that the levels of GPx and SOD were significantly reduced, along with an increase in MDA in selenium-deficient mice. Importantly, Dvl-1 and β-catenin were clearly upregulated under oxidative stress. Collectively, our findings indicate that Dvl-1 may be an underlying participant of oxidative stress induced by selenium deficiency.
Collapse
|
|
29
|
Subacute zinc administration and L-NAME caused an increase of NO, zinc, lipoperoxidation, and caspase-3 during a cerebral hypoxia-ischemia process in the rat. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:240560. [PMID: 23997853 PMCID: PMC3749594 DOI: 10.1155/2013/240560] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2013] [Accepted: 07/04/2013] [Indexed: 11/17/2022]
Abstract
Zinc or L-NAME administration has been shown to be protector agents, decreasing oxidative stress and cell death. However, the treatment with zinc and L-NAME by intraperitoneal injection has not been studied. The aim of our work was to study the effect of zinc and L-NAME administration on nitrosative stress and cell death. Male Wistar rats were treated with ZnCl2 (2.5 mg/kg each 24 h, for 4 days) and N-ω-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg) on the day 5 (1 hour before a common carotid-artery occlusion (CCAO)). The temporoparietal cortex and hippocampus were dissected, and zinc, nitrites, and lipoperoxidation were assayed at different times. Cell death was assayed by histopathology using hematoxylin-eosin staining and caspase-3 active by immunostaining. The subacute administration of zinc before CCAO decreases the levels of zinc, nitrites, lipoperoxidation, and cell death in the late phase of the ischemia. L-NAME administration in the rats treated with zinc showed an increase of zinc levels in the early phase and increase of zinc, nitrites, and lipoperoxidation levels, cell death by necrosis, and the apoptosis in the late phase. These results suggest that the use of these two therapeutic strategies increased the injury caused by the CCAO, unlike the alone administration of zinc.
Collapse
|
|
30
|
Wayhs CAY, Tortato C, Mescka CP, Pasquali MA, Schnorr CE, Nin MS, Barros HMT, Moreira JCF, Vargas CR. The association effect of insulin and clonazepam on oxidative stress in liver of an experimental animal model of diabetes and depression. PHARMACEUTICAL BIOLOGY 2013; 51:533-538. [PMID: 23368939 DOI: 10.3109/13880209.2012.747544] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/01/2023]
Abstract
CONTEXT It is known that oxidative stress occurs in peripheral blood in an experimental animal model of diabetes and depression, and acute treatment with insulin and clonazepam (CNZ) has a protective effect on oxidative stress in this model. OBJECTIVE This study evaluated the effect of insulin plus CNZ on oxidative stress parameters in the liver of diabetic male rats induced with streptozotocin (STZ) and subjected to forced swimming test (FST). MATERIALS AND METHODS Diabetes was induced by a single intraperitoneal (i.p.) dose of STZ 60 mg/kg in male Wistar rats. Insulin (4 IU/kg) plus CNZ acute i.p. treatment (0.25 mg/kg) was administered 24, 5 and 1 h before the FST. Nondiabetic control rats received i.p. injections of saline (1 mL/kg). Protein oxidative damage was evaluated by carbonyl formation and the antioxidant redox parameters were analyzed by the measurements of enzymatic activities of the superoxide dismutase (SOD), catalase and glyoxalase I (GLO). Glycemia levels also were determined. RESULTS Our present study has shown an increase in carbonyl content from diabetic rats subjected to FST (2.04 ± 0.55), while the activity of catalase (51.83 ± 19.02) and SOD (2.30 ± 1.23) were significantly decreased in liver from these animals, which were reverted by the treatment. Also, the activity of GLO (0.15 ± 0.02) in the liver of the animals was decreased. DISCUSSION AND CONCLUSION Our findings showed that insulin plus CNZ acute treatment ameliorate the antioxidant redox parameters and protect against protein oxidative damage in the liver of diabetic rats subjected to FST.
Collapse
|
|
31
|
Evaluation of antinociceptive and antioxidant properties of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one in mice. Naunyn Schmiedebergs Arch Pharmacol 2013; 386:493-505. [PMID: 23494125 PMCID: PMC3651825 DOI: 10.1007/s00210-013-0847-2] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2012] [Accepted: 02/28/2013] [Indexed: 01/05/2023]
Abstract
The aim of this study was to evaluate the influence of 3-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-dihydrofuran-2-one (LPP1) on nociceptive thresholds in mouse models of persistent pain. Influence of LPP1 on motor coordination and its antioxidant capacity in mouse brain tissue homogenates were also assessed. Pain sensitivity thresholds in animals treated with LPP1 were established using 5 % formalin solution in normoglycemic mice and in streptozotocin (STZ)-treated diabetic mice in the von Frey, hot plate, innocuous, and noxious cold water tests (water at 10 °C and 4 °C, respectively). Motor deficits were assessed in the rotarod test, whereas antioxidant capacities were evaluated using ferric reducing ability of plasma (FRAP) assay, catalase (CAT), and superoxide dismutase (SOD) activities. LPP1was antinociceptive in both phases of the formalin test, in particular, in the late phase (at doses 0.9-30 mg/kg for 66-99 % vs. control normoglycemic mice) and in a statistically significant manner increased nociceptive thresholds in response to mechanical, heat, and noxious cold stimulation in neuropathic mice (at 30 mg/kg for 274, 192, and 316 %, respectively vs. diabetic control). LPP1 did not impair motor coordination of mice in the rotarod revolving at 6 or 18 rpm. In brain tissue homogenates, it demonstrated antioxidant capacity in FRAP assay and increased SOD activity for 63 % (acute administration) and 28 % (chronic administration) vs. control. No influence on CAT activity was observed. LPP1 has significant antinociceptive properties in the formalin model and elevates pain thresholds in neuropathic mice. It has antioxidant capacity and is devoid of negative influence on animals' motor coordination.
Collapse
|
|
32
|
Fortes AC, Almeida AAC, Oliveira GAL, Santos PS, De Lucca Junior W, Mendonça Junior FJB, Freitas RM, Soares-Sobrinho JL, Soares MFR. Is oxidative stress in mice brain regions diminished by 2-[(2,6-dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile? OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2013; 2013:194192. [PMID: 23577220 PMCID: PMC3612446 DOI: 10.1155/2013/194192] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2012] [Revised: 01/11/2013] [Accepted: 01/31/2013] [Indexed: 11/23/2022]
Abstract
2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, 5TIO1, is a new 2-aminothiophene derivative with promising pharmacological activities. The aim of this study was to evaluate its antioxidant activity in different areas of mice central nervous system. Male Swiss adult mice were intraperitoneally treated with Tween 80 dissolved in 0.9% saline (control group) and 5TIO1 (0.1, 1, and 10 mg kg(-1)). Brain homogenates-hippocampus, striatum, frontal cortex, and cerebellum-were obtained after 24 h of observation. Superoxide dismutase and catalase activities, lipid peroxidation and nitrite content were measured using spectrophotometrical methods. To clarify the 5TIO1's mechanism on oxidative stress, western blot analysis of superoxide dismutase and catalase was also performed. 5TIO1 decreased lipid peroxidation and nitrite content in all brain areas and increased the antioxidant enzymatic activities, specially, in cerebellum. The data of Western blot analysis did not demonstrate evidence of the upregulation of these enzymes after the administration of this compound. Our findings strongly support that 5TIO1 can protect the brain against neuronal damages regularly observed during neuropathologies.
Collapse
Affiliation(s)
- A. C. Fortes
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
| | - A. A. C. Almeida
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
| | - G. A. L. Oliveira
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
| | - P. S. Santos
- Department of Pharmacy, Federal University of Piaui, 64.049-550 Teresina, PI, Brazil
| | - W. De Lucca Junior
- Federal University of Sergipe, Center for Biological and Health Sciences, Department of Morphology, 49.100-000 São Cristovão, SE, Brazil
| | - F. J. B. Mendonça Junior
- Laboratory of Synthesis and Vectorization of Molecules, State University of Paraiba, 58.020-540 João Pessoa, PB, Brazil
| | - R. M. Freitas
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
- Department of Pharmacy, Federal University of Piaui, 64.049-550 Teresina, PI, Brazil
| | - J. L. Soares-Sobrinho
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
- Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-520 Recife, PE, Brazil
| | - M. F. R. Soares
- Postgraduate Program in Pharmaceutical Sciences, Federal University of PI, 64.049-550 Teresina, Piauí, Brazil
- Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-520 Recife, PE, Brazil
| |
Collapse
|
|
33
|
YANG HONGYING, FAN SHOURUI, SONG DIANPING, WANG ZHUO, MA SHUNGAO, LI SHUQING, LI XIAOHONG, XU MIAN, XU MIN, WANG XIANMO. Long-term streptozotocin-induced diabetes in rats leads to severe damage of brain blood vessels and neurons via enhanced oxidative stress. Mol Med Rep 2012; 7:431-40. [DOI: 10.3892/mmr.2012.1227] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 11/15/2012] [Indexed: 01/10/2023] Open
|
|
34
|
Towner RA, Smith N, Saunders D, Henderson M, Downum K, Lupu F, Silasi-Mansat R, Ramirez DC, Gomez-Mejiba SE, Bonini MG, Ehrenshaft M, Mason RP. In vivo imaging of immuno-spin trapped radicals with molecular magnetic resonance imaging in a diabetic mouse model. Diabetes 2012; 61:2405-13. [PMID: 22698922 PMCID: PMC3447912 DOI: 10.2337/db11-1540] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2011] [Accepted: 04/05/2012] [Indexed: 01/08/2023]
Abstract
Oxidative stress plays a major role in diabetes. In vivo levels of membrane-bound radicals (MBRs) in a streptozotocin-induced diabetic mouse model were uniquely detected by combining molecular magnetic resonance imaging (mMRI) and immunotrapping techniques. An anti-DMPO (5,5-dimethyl-1-pyrroline N-oxide) antibody (Ab) covalently bound to an albumin (BSA)-Gd (gadolinium)-DTPA (diethylene triamine penta acetic acid)-biotin MRI contrast agent (anti-DMPO probe), and mMRI, were used to detect in vivo levels of DMPO-MBR adducts in kidneys, livers, and lungs of diabetic mice, after DMPO administration. Magnetic resonance signal intensities, which increase in the presence of a Gd-based molecular probe, were significantly higher within the livers, kidneys, and lungs of diabetic animals administered the anti-DMPO probe compared with controls. Fluorescence images validated the location of the anti-DMPO probe in excised tissues via conjugation of streptavidin-Cy3, which targeted the probe biotin moiety, and immunohistochemistry was used to validate the presence of DMPO adducts in diabetic mouse livers. This is the first report of noninvasively imaging in vivo levels of MBRs within any disease model. This method can be specifically applied toward diabetes models for in vivo assessment of free radical levels, providing an avenue to more fully understand the role of free radicals in diabetes.
Collapse
Affiliation(s)
- Rheal A Towner
- Advanced Magnetic Resonance Center, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
35
|
Di Naso FC, Rodrigues G, Simões Dias A, Porawski M, Fillmann H, Marroni NP. Hepatic nitrosative stress in experimental diabetes. J Diabetes Complications 2012; 26:378-81. [PMID: 22699114 DOI: 10.1016/j.jdiacomp.2012.04.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Revised: 03/29/2012] [Accepted: 04/27/2012] [Indexed: 11/26/2022]
Abstract
AIM The effects of the inhibition of nitrosative stress by aminoguanidine in an experimental model of diabetes mellitus (DM) were investigated. METHODS Twenty-one male Wistar rats were divided into three groups: control (CO), diabetic (DM), and diabetic treated with aminoguanidine (DM+AG). Aminoguanidine (aminoguanidine hemisulfate salt, Sigma Chemical Co., St. Louis, MO, USA) was used at a dose of 50 mg/kg (i.p.) during the last 30 days of the experiment. The expression levels of liver lipoperoxidation (TBARS - nmol/mg protein), inducible oxide nitric synthase (iNOS), nitrotyrosine and the NFκB nuclear transcription factor p65 were examined using western blot analysis. RESULTS The DM group demonstrated an increase in lipoperoxidation and in the expression of iNOS, nitrotyrosine and p65. Aminoguanidine reduced hepatic lipid peroxidation and protein expression levels of iNOS, nitrotyrosine and p65. CONCLUSION Aminoguanidine treatment reduces liver oxidative and nitrosative stress in diabetic animals. In addition, aminoguanidine reduced the expression of p65 in the liver.
Collapse
Affiliation(s)
- Fábio Cangeri Di Naso
- Laboratório de Fisiologia e Gastroenterologia Experimental, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS) 90035-903 Porto Alegre, RS, Brazil
| | | | | | | | | | | |
Collapse
|
|
36
|
Lao-ong T, Chatuphonprasert W, Nemoto N, Jarukamjorn K. Alteration of hepatic glutathione peroxidase and superoxide dismutase expression in streptozotocin-induced diabetic mice by berberine. PHARMACEUTICAL BIOLOGY 2012; 50:1007-12. [PMID: 22775417 DOI: 10.3109/13880209.2012.655377] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/20/2023]
Abstract
CONTEXT Diabetes mellitus (DM), a chronic disease, has been increasing and subsequently devastates the quality of life and economic status of the patients. Oxidative stress participates in development and progression of diabetes, in which levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were changed in diabetic mice. Berberine has been widely used as an alternative medicine and proved to be effective for treatment of DM and dyslipidemia. OBJECTIVE Impacts of berberine on regulation of GPx and SOD messenger RNAs (mRNAs), and glutathione (GSH) content were examined in diabetic mice to clarify its antioxidative stress potential. MATERIALS AND METHODS Noninsulin-dependent diabetes was induced in mice by a single intraperitoneal streptozotocin injection. Diabetic mice were daily treated with metformin (100 mg/kg/d) or berberine (200 mg/kg/d) for 2 weeks. The fasting blood glucose and GSH content were monitored. GPx and SOD mRNA expression were semi-quantified by reverse transcription-polymerase chain reaction. RESULTS Berberine showed the same hypoglycemic potential as metformin, a hypoglycemic drug. Interestingly, berberine did not change levels of GPx, copper-zinc SOD (CuZn-SOD), and manganese SOD (Mn-SOD) mRNA in the normal mice but significantly recovered these levels in the diabetic mice to nearly the same levels as the normal. The GSH contents, including total GSH and reduced/oxidized GSH contents, were restored to the normal level by berberine, corresponded to GPx levels. DISCUSSION AND CONCLUSION Berberine conveyed antioxidative effect via down- and up-regulation of GPx and CuZn-SOD expression, respectively. Therefore, use of berberine as a hypoglycemic compound for alternative treatment of DM could bring extra-beneficent consequence according to its antioxidative stress.
Collapse
Affiliation(s)
- Thinnakorn Lao-ong
- Academic Office for Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, National Research University-Khon Kaen University, Khon Kaen, Thailand
| | | | | | | |
Collapse
|
|
37
|
Treatment with aqueous extract from Croton cajucara Benth reduces hepatic oxidative stress in streptozotocin-diabetic rats. J Biomed Biotechnol 2012; 2012:902351. [PMID: 22811599 PMCID: PMC3395422 DOI: 10.1155/2012/902351] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2012] [Revised: 05/01/2012] [Accepted: 05/07/2012] [Indexed: 12/13/2022] Open
Abstract
Croton cajucara Benth is a plant found in Amazonia, Brazil and the bark and leaf infusion of this plant have been popularly used to treat diabetes and hepatic disorders. The present study was designed to evaluate the oxidative stress as well as the therapeutic effect of Croton cajucara Benth (1.5 mL of the C. cajucara extract i.g.) in rats with streptozotocin-induced diabetes. Croton cajucara Benth was tested as an aqueous extract for its phytochemical composition, and its antioxidant activity in vitro was also evaluated. Lipid peroxidation and superoxide dismutase, catalase, and glutathione reductase activities were measured in the hepatic tissue, as well as the presence activation of p65 (NF-κB), through western blot. Phytochemical screening of Croton cajucara Benth detected the presence of flavonoids, coumarins and alkaloids. The extract exhibited a significant antioxidant activity in the DPPH-scavenging and the hypoxanthine/xanthine oxidase assays. Liver lipid peroxidation increased in diabetic animals followed by a reduction in the Croton-cajucara-Benth-treated group. There was activation of p65 nuclear expression in the diabetic animals, which was attenuated in the animals receiving the Croton cajucara Benth aqueous extract. The liver tissue in diabetic rats showed oxidative alterations related to the streptozotocin treatment. In conclusion the Croton cajucara Benth aqueus extract treatment effectively reduced the oxidative stress and contributed to tissue recovery.
Collapse
|
|
38
|
Increased oxidative stress and imbalance in antioxidant enzymes in the brains of alloxan-induced diabetic rats. EXPERIMENTAL DIABETES RESEARCH 2012; 2012:302682. [PMID: 22645603 PMCID: PMC3356944 DOI: 10.1155/2012/302682] [Citation(s) in RCA: 64] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2011] [Revised: 02/16/2012] [Accepted: 02/21/2012] [Indexed: 01/24/2023]
Abstract
Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (SNC) as well as alterations in oxidative stress. Thus, the main objective of this study was to evaluate the effects of the animal model of diabetes induced by alloxan on memory and oxidative stress. Diabetes was induced in Wistar rats by using a single injection of alloxan (150 mg/kg), and fifteen days after induction, the rats memory was evaluated through the use of the object recognition task. The oxidative stress parameters and the activity of antioxidant enzymes, superoxide dismutase (SOD), and catalase (CAT) were measured in the rat brain. The results showed that diabetic rats did not have alterations in their recognition memory. However, the results did show that diabetic rats had increases in the levels of superoxide in the prefrontal cortex, and in thiobarbituric acid reactive species (TBARS) production in the prefrontal cortex and in the amygdala in submitochondrial particles. Also, there was an increase in protein oxidation in the hippocampus and striatum, and in TBARS oxidation in the striatum and amygdala. The SOD activity was decreased in diabetic rats in the striatum and amygdala. However, the CAT activity was increased in the hippocampus taken from diabetic rats. In conclusion, our findings illustrate that the animal model of diabetes induced by alloxan did not cause alterations in the animals' recognition memory, but it produced oxidants and an imbalance between SOD and CAT activities, which could contribute to the pathophysiology of diabetes.
Collapse
|
|
39
|
Pourkhalili N, Hosseini A, Nili-Ahmadabadi A, Hassani S, Pakzad M, Baeeri M, Mohammadirad A, Abdollahi M. Biochemical and cellular evidence of the benefit of a combination of cerium oxide nanoparticles and selenium to diabetic rats. World J Diabetes 2011; 2:204-210. [PMID: 22087357 PMCID: PMC3215770 DOI: 10.4239/wjd.v2.i11.204] [Citation(s) in RCA: 80] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2011] [Revised: 10/26/2011] [Accepted: 10/31/2011] [Indexed: 02/05/2023] Open
Abstract
AIM To study the combinative effects of nanocerium and selenium in a murine model of diabetes. METHODS Cerium oxide (CeO(2)) nanoparticles (60 mg/kg per day) and sodium selenite (5 μmol/kg per day) alone or in combination, or the metal form of CeO(2) (60 mg/kg) were administered for 2 wk by intraperitoneal injection to streptozotocin-induced diabetic rats. At the end of treatment blood was collected, liver tissue dissected and then oxidative stress markers, extent of energy depletion and lipid profile were evaluated. RESULTS Antioxidant enzymes and high density lipoprotein decreased whereas oxidative stress, adenosine diphosphate/adenosine triphospahte levels, cholesterol, triglyceride and low density lipoprotein increased on induction of diabetes. All were improved by a combination of nanocerium and sodium selenite. There was a relative amelioration by CeO(2) nanoparticles or sodium selenite alone, but the metal form of CeO(2) showed no significant improvement. CONCLUSION The combination of nanocerium and sodium selenite is more effective than either alone in improving diabetes-induced oxidative stress.
Collapse
Affiliation(s)
- Nazila Pourkhalili
- Nazila Pourkhalili, Amir Nili-Ahmadabadi, Shokoufeh Hassani, Mohsen Pakzad, Maryam Baeeri, Azadeh Mohammadirad, Mohammad Abdollahi, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical sciences, Tehran 1417614411, Iran
| | | | | | | | | | | | | | | |
Collapse
|