|
1
|
Zhu X, Chen C, Liu Q, Zhu Z, Wu X, Zhang Y. Multiple pesticide exposure and impaired glucose regulation in U.S. non-diabetic population. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2025; 366:125519. [PMID: 39672370 DOI: 10.1016/j.envpol.2024.125519] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/14/2024] [Revised: 11/28/2024] [Accepted: 12/09/2024] [Indexed: 12/15/2024]
Abstract
Prediabetes is a serious metabolic disorder that is often overlooked and 70% of individuals with prediabetes would eventually develop type 2 diabetes. The diabetogenic effects of pesticides have been reported in toxicological studies but their association with prediabetes is rarely investigated. We aimed to evaluate the association between pesticide exposure and impaired glucose regulation (IGR), including prediabetes (defined as impaired fasting glucose [IFG] and/or impaired glucose tolerance [IGT]) and insulin resistance, in a general U.S. non-diabetic population. Three classes of urinary pesticides, including organophosphorus pesticides (OPs), pyrethroid, and herbicides were measured. Generalized linear regression, restricted cubic spline, and Bayesian kernel machine regression (BKMR) models were combined to evaluate their associations. 3,5,6-trichloropyridinol (TCPY) was positively associated with prediabetes and IGT (highest vs lowest TCPY quartile: prediabetes: OR: 1.97, 95% CI: 1.18, 3.31; IGT: OR: 2.03, 95% CI: 1.14, 3.66) in a linear dose-response manner (P for nonlinear<0.05). Another two metabolites of OPs, malathion dicarboxylic acid (MDCA) diacid and para-nitrophenol (PNP), were found to increase the odds ratio of insulin resistance (PNP: OR: 1.22, 95% CI: 1.05, 1.42; MDCA: OR: 1.36, 95% CI: 1.08, 1.70) with linear dose-response curves (P for nonlinear<0.05). Considering mutual exposure to multiple pesticides, TCPY, MDCA, and PNP made the most contributions in the mixture exposure and IGR. No obvious interactions among pesticides were found in the multiple exposure settings. The odds ratio of TCPY exposure and prediabetes was increased with advancing age but not related to body mass index (BMI). The results remained robust in sensitivity analysis with restricted participants without abnormal urinary creatinine and unsteady glucose or insulin levels. Our findings suggested the close relationship between OPs and impaired glucose regulation, especially in older adults, which provides insights into the prevention of diabetes at the earlier stage.
Collapse
Affiliation(s)
- Xingdi Zhu
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China; First School of Clinical Medicine, Nanjing Medical University, Nanjing, 211100, China
| | - Congxin Chen
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China
| | - Qi Liu
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China
| | - Zhihong Zhu
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China
| | - Xiaoli Wu
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China
| | - Yuqing Zhang
- Department of Obstetrics and Gynecology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, 210004, China.
| |
Collapse
|
|
2
|
Chung YL, Hou YC, Wang IK, Lu KC, Yen TH. Organophosphate pesticides and new-onset diabetes mellitus: From molecular mechanisms to a possible therapeutic perspective. World J Diabetes 2021; 12:1818-1831. [PMID: 34888010 PMCID: PMC8613664 DOI: 10.4239/wjd.v12.i11.1818] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/27/2021] [Accepted: 09/22/2021] [Indexed: 02/06/2023] Open
Abstract
Organophosphate is a commonly used pesticide in the agricultural sector. The main action of organophosphate focuses on acetylcholinesterase inhibition, and it therefore contributes to acute cholinergic crisis, intermediate syndrome and delayed neurotoxicity. From sporadic case series to epidemiologic studies, organophosphate has been linked to hyperglycemia and the occurrence of new-onset diabetes mellitus. Organophosphate-mediated direct damage to pancreatic beta cells, insulin resistance related to systemic inflammation and excessive hepatic gluconeogenesis and polymorphisms of the enzyme governing organophosphate elimination are all possible contributors to the development of new-onset diabetes mellitus. To date, a preventive strategy for organophosphate-mediated new-onset diabetes mellitus is still lacking. However, lowering reactive oxygen species levels may be a practical method to reduce the risk of developing hyperglycemia.
Collapse
Affiliation(s)
- Ya-Ling Chung
- Department of Medical Laboratory, Cardinal-Tien Hospital, New Taipei City 231, Taiwan
| | - Yi-Chou Hou
- Department of Internal Medicine, Cardinal Tien Hospital, New Taipei City 231, Taiwan
- Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
- School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
| | - I-Kuan Wang
- Department of Nephrology, China Medical University Hospital, Taichung 404, Taiwan
- College of Medicine, China Medical University, Taichung 404, Taiwan
| | - Kuo-Cheng Lu
- School of Medicine, Fu Jen Catholic University, New Taipei City 24205, Taiwan
- Division of Nephrology, Department of Medicine, Fu Jen Catholic University Hospital, New Taipei City 242, Taiwan
- Division of Nephrology, Department of Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan
| | - Tzung-Hai Yen
- Department of Nephrology, Chang Gung Memorial Hospital, Linkou 333, Taiwan
- School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| |
Collapse
|
|
3
|
Cobilinschi C, Tincu R, Băetu A, Deaconu C, Totan A, Rusu A, Neagu P, Grințescu I. ENDOCRINE DISTURBANCES INDUCED BY LOW-DOSE ORGANOPHOSPHATE EXPOSURE IN MALE WISTAR RATS. ACTA ENDOCRINOLOGICA (BUCHAREST, ROMANIA : 2005) 2021; 17:177-185. [PMID: 34925565 PMCID: PMC8665251 DOI: 10.4183/aeb.2021.177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Organophosphate exposure induces many endocrine effects. AIM In this study we observed the effects of acute stress induced by cholinesterase inhibition on the main hormonal axes. MATERIALS AND METHODS We included thirteen weanling Wistar rats that were subjected to organophosphate exposure. They were first tested for baseline levels of butyrylcholinesterase, cortisol, free triiodothyronine, thyroxine, thyroid-stimulating hormone and prolactin. Secondly, chlorpyrifos was administered. Next samples were taken to determine the level of all the above-mentioned parameters. RESULTS Butyrylcholinesterase was significantly decreased after exposure (p<0.001). Cortisol levels were significantly higher after clorpyrifos administration (358.75±43 vs. 241.2±35 nmoL/L)(p<0.01). Although prolactin had a growing trend (450.25±24.65 vs. 423±43.4 uI/mL), the results were not statistically significant. Both free triiodothyronine and thyroxine were significantly higher after exposure. Surprisingly, thyroid-stimulating hormone level almost doubled after exposure with high statistical significance (p<0.001), suggesting a central stimulation of thyroid axis. Butyrylcholinesterase level was proportional with thyroid-stimulating hormone level (p=0.02) and thyroxine level was inversely correlated to the cortisol level (p=0.01). Acute cholinesterase inhibition may induce high levels of cortisol, free triiodothyronine, thyroxine and thyroid-stimulating hormone. From our knowledge this is the first study dedicated to the assessment of acute changes of hormonal status in weanling animals after low-dose organophosphate exposure.Conclusion. Acute cholinesterase inhibition may cause acute phase hormonal disturbances specific to shocked patients.
Collapse
Affiliation(s)
- C. Cobilinschi
- “Carol Davila” University of Medicine and Pharmacy - Anesthesiology and Intensive Care - Bucharest, Romania
- Bucharest Emergency Hospital - Anesthesiology and Intensive Care - Bucharest, Romania
| | - R.C. Tincu
- Bucharest Emergency Hospital - Intensive Care Toxicology Unit - Bucharest, Romania
| | - A.E. Băetu
- “Carol Davila” University of Medicine and Pharmacy - Anesthesiology and Intensive Care - Bucharest, Romania
- Bucharest Emergency Hospital - Anesthesiology and Intensive Care - Bucharest, Romania
| | - C.O. Deaconu
- “Carol Davila” University of Medicine and Pharmacy - Internal Medicine and Rheumatology - Bucharest, Romania
| | - A. Totan
- “Carol Davila” University of Medicine and Pharmacy - Biochemistry - Bucharest, Romania
| | - A. Rusu
- Bucharest Emergency Hospital - Anesthesiology and Intensive Care - Bucharest, Romania
| | - P.T. Neagu
- “Carol Davila” University of Medicine and Pharmacy - Plastic surgery, Bucharest, Romania
- Bucharest Emergency Hospital - Plastic surgery, Bucharest, Romania
| | - I.M. Grințescu
- “Carol Davila” University of Medicine and Pharmacy - Anesthesiology and Intensive Care - Bucharest, Romania
- Bucharest Emergency Hospital - Anesthesiology and Intensive Care - Bucharest, Romania
| |
Collapse
|
|
4
|
Chronic Exposure to Organophosphates Pesticides and Risk of Metabolic Disorder in Cohort from Pakistan and Cameroon. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18052310. [PMID: 33652791 PMCID: PMC7967685 DOI: 10.3390/ijerph18052310] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 02/12/2021] [Accepted: 02/19/2021] [Indexed: 12/23/2022]
Abstract
(1) Background: Organophosphorus pesticides (OPPs) are major chemicals used in agriculture for eradication of insecticides/pesticides. Unfortunately, the longtime exposure of human beings to OPPs could lead to metabolic disorder such as high blood pressure, hyperglycemia, overweight or dyslipidemia. The aim of this research is to evaluate the possible metabolic dysregulations as a consequence of chronic OPPs exposure to individuals in Cameroon and Pakistan. (2) Methods: Blood samples were collected from 300 participants in each country, into ethylenediaminetetraacetic acid (EDTA) tubes. The samples were extracted with solid phase extraction (methanol/water) for analysis of OPPs with gas chromatography mass spectrometry. The spectrophotometry and Enzyme Linked ImmunoSorbent Assay (ELISA) were used to measure the hepatic, renal, pancreatic and cardiovascular functions. The atherogenic index (AI) was also determined in OPPs exposed and nonexposed cohorts. (3) Results: The results showed the presence of malathion, parathion and chlorpyrifos OPPs residues in Cameroonians, and malathion and chlorpyrifos in Pakistani samples, respectively. Elevated Body Mass Index (BMI), insulin, blood glucose, dyslipidemia and hypertension were noted in OPPs chronic exposed groups. In addition, dysregulated liver and kidney function profiles were observed in all participants regardless of gender and age groups. (4) Conclusions: The study concludes that both the study cohorts showed several metabolic dysregulations attributable to chronic exposure to a mixture of OPPs which may provide precursors for establishment of metabolic syndrome and other chronic diseases. Further different extended population-based studies are suggested to understand the differential metabolic dysfunctions caused by structurally different OPPs mixtures exposure.
Collapse
|
|
5
|
Leonel Javeres MN, Raza S, Judith N, Anwar F, Habib R, Batool S, Nurulain SM. Mixture of Organophosphates Chronic Exposure and Pancreatic Dysregulations in Two Different Population Samples. Front Public Health 2020; 8:534902. [PMID: 33194944 PMCID: PMC7655777 DOI: 10.3389/fpubh.2020.534902] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Accepted: 08/20/2020] [Indexed: 12/13/2022] Open
Abstract
Organophosphates (OP) are a major agrochemical. The application of OP pesticides is expected to increase multifold in the coming decades. The etiology of diabetic diseases is attributed to multiple factors including OP pesticide exposure. The present study investigates pancreatic dysregulation with respect to exocrine enzymes and diabesity in groups of Pakistani and Cameroonian people exposed to a mixture of OP pesticides. Nine hundred and four OP exposed individuals were enrolled for this cross-sectional study after due consent and approval from an ethical review committee. Pesticides' residues were measured by GC-MS spectrometry. Cholinergic enzymes were measured by Elman's method. Serum glucose, insulin, serum amylase, lipase, and triglyceride were measured by spectrophotometry and ELISA; HOMA-IR was determined in OP exposed and non-exposed participants. Stata 15 and R 3.2.0 software were used for statistical analysis of the data. Malathion, chlorpyrifos, and parathion residues were evident in plasma samples. RBC-acetylcholinesterase was significantly depressed in OP exposed groups. In both population samples, investigated pancreatic functions were found to be statistically significantly more dysregulated than non-exposed. OP exposure indicated risk of diabetes and insulin, glycaemia, adiponectin, triglycerides, and TNF-α dysregulations. The study concludes that both OP exposed population groups exhibited a mixture of OP residues and pancreatic dysregulation, although the effect was more pronounced in the Cameroonian population. In addition, serum lipase has a positive correlation with OP exposure and diabetes and may be suggested as an alternate/additional diagnostic marker for diabesity under OP exposure. However, screening of other environmental co-factors with OP for pancreatic dysregulation is suggested.
Collapse
Affiliation(s)
| | - Saqlain Raza
- Department of Mathematics, COMSATS University Islamabad, Islamabad, Pakistan
| | - Ngondi Judith
- Department of Biochemistry, Yaoundé I University, Yaoundé, Cameroon
| | - Fozia Anwar
- Department of Health Informatic, COMSATS University Islamabad, Islamabad, Pakistan
| | - Rabia Habib
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
| | - Sajida Batool
- Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
| | | |
Collapse
|
|
6
|
Onaru K, Ohno S, Kubo S, Nakanishi S, Hirano T, Mantani Y, Yokoyama T, Hoshi N. Immunotoxicity evaluation by subchronic oral administration of clothianidin in Sprague-Dawley rats. J Vet Med Sci 2020; 82:360-372. [PMID: 31983703 PMCID: PMC7118483 DOI: 10.1292/jvms.19-0689] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
Neonicotinoid pesticides (NNs) act as agonists on nicotinic acetylcholine receptors (nAChRs) of insects, and there have been concerns about the effects of NNs on the health of mammals.
Since nAChRs are expressed in immune cells, it is possible that NNs disturb the immune system. However, few reports have examined the immunotoxicity of clothianidin (CLO), a
widely-used NN. Here, we report the effects of CLO on immune organs and type IV allergic reactions in ear auricles. We orally administered CLO at 0, 30 and 300 mg/kg/day
(CLO-0, 30 and 300) to Sprague-Dawley rats for 28 days. The effects were evaluated by organ and body weights, histopathology, and immunohistochemistry (TCRαβ, CD4, CD8,
CD11b, CD68, CD103). In addition, some cecal contents were subjected to preliminary gut microbiota analysis, because microbiota contribute to host homeostasis, including the immunity. Our
results showed loose stool, suppression of body weight gain, significant changes in organ weights (thymus: decreased; liver: increased) and changes of the gut microbiota in the
CLO-300 group. There were no obvious histopathological changes in immune organs. Granulomas of the ear auricles were found in one rat of each of the
CLO-30 and 300 groups, but CLO had no apparent effect on the thickness or immunohistochemistry in the ear auricles. We present new evidence that CLO affects the thymus and
intestine, and might enhance the local inflammatory response. These findings should contribute to the appropriate evaluation of the safety of NNs in the future.
Collapse
Affiliation(s)
- Kanoko Onaru
- Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Shuji Ohno
- Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Shizuka Kubo
- Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Satoki Nakanishi
- Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Tetsushi Hirano
- Division of Drug and Structural Research, Life Science Research Center, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan
| | - Youhei Mantani
- Laboratory of Histophysiology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Toshifumi Yokoyama
- Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| | - Nobuhiko Hoshi
- Laboratory of Animal Molecular Morphology, Department of Animal Science, Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada, Kobe, Hyogo 657-8501, Japan
| |
Collapse
|
|
7
|
Lakshmi J, Mukhopadhyay K, Ramaswamy P, Mahadevan S. A Systematic Review on Organophosphate Pesticide and Type II Diabetes Mellitus. Curr Diabetes Rev 2020; 16:586-597. [PMID: 31544698 DOI: 10.2174/1573399815666190712192844] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 04/25/2019] [Accepted: 06/22/2019] [Indexed: 12/17/2022]
Abstract
Organophosphate (OP) pesticides are extremely poisonous and they affect the glucose breakdown in numerous and mechanism. There are higher evidence of stimulating diabetes mellitus through OP pesticides especially the type II diabetes. The upsurge in the level of glucose (hyperglycemia), and insulin resistance along with their related outcomes are discussed in this review. The data related to investigational and clinical techniques endorse a connection amid such molecular mechanism and compounds of OPs. Numerous studies conducted till March 2018 have reported OP' exposures and diabetes-related outcomes. The acute and chronic exposure in case of these insecticides and diabetesrelated outcomes are defined in this study. Initially, it was declared that OPs prompt to hyperglycemia. Then, a high association of glucose in blood beside insulin was found out. The affirmation from some clinical as well as investigational studies supported a connection amid exposure to OP and diabetes, yet in maximum number of instances, non-specific diabetes occurs.
Collapse
Affiliation(s)
- Jothi Lakshmi
- Department of Environmental Health Engineering, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Krishnendu Mukhopadhyay
- Department of Environmental Health Engineering, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Padmavathi Ramaswamy
- Department of Physiology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| | - Shriraam Mahadevan
- Department of Endocrinology, Sri Ramachandra Medical College and Research Institute, Chennai, India
| |
Collapse
|
|
8
|
Czajka M, Matysiak-Kucharek M, Jodłowska-Jędrych B, Sawicki K, Fal B, Drop B, Kruszewski M, Kapka-Skrzypczak L. Organophosphorus pesticides can influence the development of obesity and type 2 diabetes with concomitant metabolic changes. ENVIRONMENTAL RESEARCH 2019; 178:108685. [PMID: 31479978 DOI: 10.1016/j.envres.2019.108685] [Citation(s) in RCA: 69] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 08/09/2019] [Accepted: 08/21/2019] [Indexed: 06/10/2023]
Abstract
Widespread use and the bioaccumulation of pesticides in the environment lead to the contamination of air, water, soil and agricultural resources. A huge body of evidence points to the association between the pesticide exposure and increase in the incidence of chronic diseases, e.g. cancer, birth defects, reproductive disorders, neurodegenerative, cardiovascular and respiratory diseases, developmental disorders, metabolic disorders, chronic renal disorders or autoimmune diseases. Organophosphorus compounds are among the most widely used pesticides. A growing body of evidence is suggesting the potential interdependence between the organophosphorus pesticides (OPs) exposure and risk of obesity and type 2 diabetes mellitus (T2DM). This article reviews the current literature to highlight the latest in vitro and in vivo evidences on the possible influence of OPs on obesity and T2DM development, as well as epidemiological evidence for the metabolic toxicity of OPs in humans. The article also draws attention to the influence of maternal OPs exposure on offspring. Summarized studies suggest that OPs exposure is associated with metabolic changes linked with obesity and T2DM indicated that such exposures may increase risk or vulnerability to other contributory components.
Collapse
Affiliation(s)
- Magdalena Czajka
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland.
| | - Magdalena Matysiak-Kucharek
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland
| | - Barbara Jodłowska-Jędrych
- Department of Histology and Embryology with Experimental Cytology Unit, Medical University of Lublin, 20-080, Lublin, Poland
| | - Krzysztof Sawicki
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland
| | - Berta Fal
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland
| | - Bartłomiej Drop
- Department of Medical Informatics and Statistics with E-learning Lab, Medical University of Lublin, 20-090, Lublin, Poland
| | - Marcin Kruszewski
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland; Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, Dorodna 16, 03-195, Warsaw, Poland
| | - Lucyna Kapka-Skrzypczak
- Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090, Lublin, Poland.
| |
Collapse
|
|
9
|
Yang JS, Park Y. Insecticide Exposure and Development of Nonalcoholic Fatty Liver Disease. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:10132-10138. [PMID: 30193066 DOI: 10.1021/acs.jafc.8b03177] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is the prevalent liver disease resulting from metabolic disorder, which is highly associated with obesity and type 2 diabetes. Emerging evidence has shown that insecticide exposure disrupts lipid and glucose metabolism and results in obesity and type 2 diabetes. However, the potential impact of insecticide exposure on the liver functions related to NAFLD development is largely unknown. Thus, this perspective focused on the current knowledge of the effect of insecticides on the liver functions, particularly lipid and glucose metabolism, as well as other liver functions to correlate insecticide exposure and the development of NAFLD.
Collapse
Affiliation(s)
- Jason S Yang
- Department of Food Science , University of Massachusetts Amherst , 102 Holdsworth Way , Amherst , Massachusetts 01003 , United States
| | - Yeonhwa Park
- Department of Food Science , University of Massachusetts Amherst , 102 Holdsworth Way , Amherst , Massachusetts 01003 , United States
| |
Collapse
|
|
10
|
Zhang J, Song W, Sun Y, Cheng B, Shan A. Changes in glucose metabolism and mRNA expression of IRS-2 in rats exposed to phoxim and the protective effects of vitamin E. Toxicol Res (Camb) 2018; 7:201-210. [PMID: 30090575 PMCID: PMC6061297 DOI: 10.1039/c7tx00243b] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2017] [Accepted: 11/22/2017] [Indexed: 11/21/2022] Open
Abstract
Research has shown that organophosphorus pesticides impair glucose homeostasis and cause insulin resistance and type 2 diabetes. The current study investigates the influence of phoxim on insulin signaling pathways and the protective effects of vitamin E. Phoxim (180 mg kg-1) and VE (200 mg kg-1) were administered orally to Sprague-Dawley rats over a period of 28 consecutive days. After exposure to phoxim, the animals showed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin. Phoxim increases the fasting glucose, insulin and cholesterol levels, as well as the liver hexokinase activity (HK) significantly while decreasing the high density lipoprotein (HDL) cholesterol, and glycogen content in the liver and skeletal muscles observably. Furthermore, we observed an increase of insulin resistance biomarkers and a decrease of insulin sensitivity indices. The insulin receptor substrate (IRS)-2 mRNA expressions of liver and skeletal muscles were down-regulated by phoxim, while the expression of IRS-1 showed no difference. There were no differences in triglycerides, LDL-cholesterol, and fasting glucose treated with phoxim. On the basis of biochemical and molecular findings, phoxim has been determined to impair glucose homeostasis through insulin resistance and insulin signaling pathway disruptions resulting in a reduced function of insulin in hepatocytes and muscles. VE supplementation reduced the fasting glucose, increased the glycogen content and HDL-cholesterol, but did not reduce the insulin resistance indices, when phoxim-treated rats were compared to VE supplemented rats. Overall, this study shows that vitamin E modifies the phoxim toxicity in rats only to a moderate degree.
Collapse
Affiliation(s)
- Jing Zhang
- Institute of Animal Nutrition , Northeast Agricultural University , Harbin , 150030 , P. R. China . ; ; Tel: +86 0451 5519 0685
| | - Wentao Song
- Institute of Animal Nutrition , Northeast Agricultural University , Harbin , 150030 , P. R. China . ; ; Tel: +86 0451 5519 0685
| | - Yuecheng Sun
- Institute of Animal Nutrition , Northeast Agricultural University , Harbin , 150030 , P. R. China . ; ; Tel: +86 0451 5519 0685
| | - Baojing Cheng
- Institute of Animal Nutrition , Northeast Agricultural University , Harbin , 150030 , P. R. China . ; ; Tel: +86 0451 5519 0685
| | - Anshan Shan
- Institute of Animal Nutrition , Northeast Agricultural University , Harbin , 150030 , P. R. China . ; ; Tel: +86 0451 5519 0685
| |
Collapse
|
|
11
|
Ramirez-Vargas MA, Flores-Alfaro E, Uriostegui-Acosta M, Alvarez-Fitz P, Parra-Rojas I, Moreno-Godinez ME. Effects of exposure to malathion on blood glucose concentration: a meta-analysis. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2018; 25:3233-3242. [PMID: 29235025 DOI: 10.1007/s11356-017-0890-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2017] [Accepted: 11/29/2017] [Indexed: 06/07/2023]
Abstract
Exposure to malathion (an organophosphate pesticide widely used around the world) has been associated with alterations in blood glucose concentration in animal models. However, the results are inconsistent. The aim of this meta-analysis was to evaluate whether malathion exposure can disturb the concentrations of blood glucose in exposed rats. We performed a literature search of online databases including PubMed, EBSCO, and Google Scholar and reviewed original articles that analyzed the relation between malathion exposure and glucose levels in animal models. The selection of articles was based on inclusion and exclusion criteria. The database search identified thirty-five possible articles, but only eight fulfilled our inclusion criteria, and these studies were included in the meta-analysis. The effect of malathion on blood glucose concentration showed a non-monotonic dose-response curve. In addition, pooled analysis showed that blood glucose concentrations were 3.3-fold higher in exposed rats than in the control group (95% CI, 2-5; Z = 3.9; p < 0.0001) in a random-effect model. This result suggested that alteration of glucose homeostasis is a possible mechanism of toxicity associated with exposure to malathion.
Collapse
Affiliation(s)
- Marco Antonio Ramirez-Vargas
- Laboratorio De Toxicología y Salud Ambiental, Facultad De Ciencias Químico Biológicas, Universidad Autónoma De Guerrero, Av. Lázaro Cárdenas s/n, Ciudad Universitaria, 39070, Chilpancingo, Guerrero, Mexico
| | - Eugenia Flores-Alfaro
- Laboratorio De Investigación En Epidemiologia Clínica y Molecular, Facultad De Ciencias Químico Biológicas, Universidad Autónoma De Guerrero, Chilpancingo, Mexico
| | - Mayrut Uriostegui-Acosta
- Laboratorio de Inmunotoxicogenómica, Escuela Superior de Ciencias Naturales, Universidad Autónoma De Guerrero, Chilpancingo, Mexico
| | - Patricia Alvarez-Fitz
- Laboratorio De Toxicología y Salud Ambiental, Facultad De Ciencias Químico Biológicas, Universidad Autónoma De Guerrero, Av. Lázaro Cárdenas s/n, Ciudad Universitaria, 39070, Chilpancingo, Guerrero, Mexico
| | - Isela Parra-Rojas
- Laboratorio De Investigación En Obesidad y Diabetes, Facultad De Ciencias Químico Biológicas, Universidad Autónoma De Guerrero, Chilpancingo, Mexico
| | - Ma Elena Moreno-Godinez
- Laboratorio De Toxicología y Salud Ambiental, Facultad De Ciencias Químico Biológicas, Universidad Autónoma De Guerrero, Av. Lázaro Cárdenas s/n, Ciudad Universitaria, 39070, Chilpancingo, Guerrero, Mexico.
| |
Collapse
|
|
12
|
Karami-Mohajeri S, Ahmadipour A, Rahimi HR, Abdollahi M. Adverse effects of organophosphorus pesticides on the liver: a brief summary of four decades of research. Arh Hig Rada Toksikol 2018; 68:261-275. [DOI: 10.1515/aiht-2017-68-2989] [Citation(s) in RCA: 50] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2017] [Accepted: 12/01/2017] [Indexed: 01/20/2023] Open
Abstract
Abstract
Organophosphorus pesticides (OPs) are widely used volatile pesticides that have harmful effects on the liver in acute and chronic exposures. This review article summarises and discusses a wide collection of studies published over the last 40 years reporting on the effects of OPs on the liver, in an attempt to propose general mechanisms of OP hepatotoxicity and possible treatment. Several key biological processes have been reported as involved in OP-induced hepatotoxicity such as disturbances in the antioxidant defence system, oxidative stress, apoptosis, and mitochondrial and microsomal metabolism. Most studies show that antioxidants can attenuate oxidative stress and the consequent changes in liver function. However, few studies have examined the relationship between OP structures and the severity and mechanism of their action. We hope that future in vitro, in vivo, and clinical trials will answer the remaining questions about the mechanisms of OP hepatotoxicity and its management.
Collapse
Affiliation(s)
- Somayyeh Karami-Mohajeri
- Pharmaceutics Research Center, Institute of Neuropharmacology, Tehran , Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran , Iran
| | - Ahmad Ahmadipour
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran , Iran
| | - Hamid-Reza Rahimi
- Pharmaceutics Research Center, Institute of Neuropharmacology, Tehran , Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran , Iran
| | - Mohammad Abdollahi
- Kerman University of Medical Sciences, Kerman , Pharmaceutical Sciences Research Center, Iran
- Department of Toxicology and Pharmacology4, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran , Iran
| |
Collapse
|
|
13
|
Taurine alleviates malathion induced lipid peroxidation, oxidative stress, and proinflammatory cytokine gene expressions in rats. Biomed Pharmacother 2017; 96:263-268. [DOI: 10.1016/j.biopha.2017.09.141] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2017] [Revised: 09/26/2017] [Accepted: 09/26/2017] [Indexed: 12/26/2022] Open
|
|
14
|
Xiao X, Clark JM, Park Y. Potential contribution of insecticide exposure and development of obesity and type 2 diabetes. Food Chem Toxicol 2017; 105:456-474. [PMID: 28487232 DOI: 10.1016/j.fct.2017.05.003] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2017] [Revised: 04/13/2017] [Accepted: 05/03/2017] [Indexed: 12/18/2022]
Abstract
The introduction of insecticides has greatly improved agricultural productivity and human nutrition; however, the wide use of insecticides has also sparked growing concern over their health impacts. Increased rate of cancers, neurodegenerative disorders, reproductive dysfunction, birth defects, respiratory diseases, cardiovascular diseases and aging have been linked with insecticide exposure. Meanwhile, a growing body of evidence is suggesting that exposure to insecticides can also potentiate the risk of obesity and type 2 diabetes. This review summarizes the relationship between insecticide exposure and development of obesity and type 2 diabetes using epidemiological and rodent animal studies, including potential mechanisms. The evidence as a whole suggests that exposure to insecticides is linked to increased risk of obesity and type 2 diabetes.
Collapse
Affiliation(s)
- Xiao Xiao
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA
| | - John M Clark
- Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst 01003, MA, USA
| | - Yeonhwa Park
- Department of Food Science, University of Massachusetts, Amherst, MA 01003, USA.
| |
Collapse
|
|
15
|
Flehi-Slim I, Chargui I, Boughattas S, El Mabrouk A, Belaïd-Nouira Y, Neffati F, Najjar MF, Haouas Z, Ben Cheikh H. Malathion-induced hepatotoxicity in male Wistar rats: biochemical and histopathological studies. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2015; 22:17828-17838. [PMID: 26162445 DOI: 10.1007/s11356-015-5014-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/19/2015] [Accepted: 07/01/2015] [Indexed: 06/04/2023]
Abstract
The increasing use of organophosphorus pesticides in the environment constitutes an ecotoxicological hazard especially for humans and non-target animals. Hereby, we analyzed the toxic effects of malathion on the histological structure of liver and biochemical parameters in male rats. Three groups received daily different amounts of malathion: 1/1000, 1/100, and 1/10 LD50 for 30 days. The weights of treated rat's liver have increased. Analyzed tissues showed centrilobular and sinusoidal congestion, hepatocyte hypertrophy, cellular vacuolization, anucleated hepatocytes, depletion of organelles affecting the majority of cells, and presence of necrotic foci into the hepatic parenchyma. Histological sections of the liver showed important hepatocyte glycogen storage. We conclude that malathion stimulates the filing of glycogen in a dose-dependent manner. Biochemical parameters showed that alanine transaminase (ALT), aspartate transaminase (AST), gamma glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) levels increased in the treated groups when the level of total protein decreased in intoxicated groups.
Collapse
Affiliation(s)
- Imen Flehi-Slim
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| | - Issam Chargui
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| | - Sonia Boughattas
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia.
| | - Aymen El Mabrouk
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| | - Yosra Belaïd-Nouira
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| | - Fadwa Neffati
- Laboratory of Biochemistry-Toxicology, University Hospital of Monastir, Monastir, Tunisia
| | - Mohamed Fadhel Najjar
- Laboratory of Biochemistry-Toxicology, University Hospital of Monastir, Monastir, Tunisia
| | - Zohra Haouas
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| | - Hassen Ben Cheikh
- Laboratory of Histology and Cytogenetic, Faculty of Medicine, Research Unity of Genetic (02/UR/08-03), Avenue Ibnou Sina 5000, Monastir, Tunisia
| |
Collapse
|
|
16
|
Rezg R, Mornagui B, Santos JSDO, Dulin F, El-Fazaa S, Ben El-Haj N, Bureau R, Gharbi N. Protective effects of caffeic acid against hypothalamic neuropeptides alterations induced by malathion in rat. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2015; 22:6198-6207. [PMID: 25404496 DOI: 10.1007/s11356-014-3824-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2014] [Accepted: 11/05/2014] [Indexed: 06/04/2023]
Abstract
Exposure to pesticides is suspected to cause human health problems. Our study aimed to evaluate preventive effects of caffeic acid (3,4-dihydroxycinnamic acid) in the hypothalamus against malathion-induced neuropeptides gene expression alterations. Malathion at 100 mg/kg was administered intragastrically to rats alone or in combination with caffeic acid at 100 mg/kg during 4 weeks. A molecular expression of hypothalamic neuropeptides and plasmatic cholinesterase activity was investigated. Furthermore, we used in silico analysis, known as computational docking, to highlight the nature of acetylcholinesterase-malathion/caffeic acid interactions. Our findings showed differences in the responses and indicate that caffeic acid reversed malathion-induced decrease in corticotropin-releasing hormone mRNA but not brain-derived neurotrophic factor which presented an increased tendency. We suggest that caffeic acid can interact with acetylcholinesterase as the primary target of organophosphorus compounds. Results predict that caffeic acid can block partly the acetylcholinesterase gorge entrance via π-π stacking interaction with Tyr 124 and Trp 286 residues of the peripheral site leading to its stricture. Under this condition, we suggested that acetylcholine trafficking toward the catalytic site is ameliorated compared to malaoxon according to their sizes.
Collapse
Affiliation(s)
- Raja Rezg
- Laboratoire de Physiologie des Agressions, Département de Biologie, Faculté des Sciences de Tunis, Université El Manar, Tunis, Tunisie
| | | | | | | | | | | | | | | |
Collapse
|
|
17
|
Lasram MM, Dhouib IB, Bouzid K, Lamine AJ, Annabi A, Belhadjhmida N, Ahmed MB, Fazaa SE, Abdelmoula J, Gharbi N. Association of inflammatory response and oxidative injury in the pathogenesis of liver steatosis and insulin resistance following subchronic exposure to malathion in rats. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2014; 38:542-53. [PMID: 25180440 DOI: 10.1016/j.etap.2014.08.007] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/16/2013] [Revised: 08/05/2014] [Accepted: 08/07/2014] [Indexed: 05/19/2023]
Abstract
Insulin resistance and risk of type 2 diabetes are the most important complications following exposure to organophosphorous (OPs) pesticides. Regarding the importance of liver on metabolic pathways regulation, in particular blood glucose homeostasis, we focused on liver inflammation and oxidative damages in a subchronic model of toxicity by malathion. Adult male Wistar rats of body weight 200-250g were used for the study. Malathion (200mg/kg b.w./day) was administered to rats by oral intubation for 28 days. Glycemic and insulin resistance indices, markers of liver injury, markers of inflammation and oxidative stress were assessed. Malathion-treated rats showed increased glycemia, insulinemia and glycated hemoglobin level, HOMA-IR and HOMA-β indices, plasma activities of hepatocellular enzymes, lipid peroxidation index, CD3(+)/CD4(+) and CD3(+)/CD4(+) and pro-inflammatory cytokines when decreased antioxidant status in liver was noted. Most of our study indicates that malathion promotes insulin resistance, inflammation and Hepatosteatosis in subchronic model of exposure. On the basis of biochemical and molecular findings, it is concluded that insulin resistance induced by malathion occurs through oxidative stress and related pro-inflammatory markers in a way to result in a reduced function of insulin in liver cells.
Collapse
Affiliation(s)
- Mohamed Montassar Lasram
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
| | - Ines Bini Dhouib
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia; Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia
| | - Kahna Bouzid
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
| | - Aicha Jrad Lamine
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia
| | - Alya Annabi
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia
| | - Nadia Belhadjhmida
- Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia
| | - Malika Ben Ahmed
- Laboratory of Clinical Immunology, Pasteur Institute of Tunis, Tunis, Tunisia
| | - Saloua El Fazaa
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
| | - Jaouida Abdelmoula
- Laboratory of Clinical Biochemistry, Charles Nicolle Hospital, Tunis, Tunisia
| | - Najoua Gharbi
- Laboratory of Aggression Physiology and Endocrine Metabolic Studies, Department of Biology, Faculty of Sciences, Tunis, Tunisia.
| |
Collapse
|
|
18
|
Lasram MM, Dhouib IB, Annabi A, El Fazaa S, Gharbi N. A review on the molecular mechanisms involved in insulin resistance induced by organophosphorus pesticides. Toxicology 2014; 322:1-13. [DOI: 10.1016/j.tox.2014.04.009] [Citation(s) in RCA: 65] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2014] [Revised: 04/23/2014] [Accepted: 04/24/2014] [Indexed: 02/06/2023]
|
|
19
|
Ibrahim ATA, Harabawy ASA. Sublethal toxicity of carbofuran on the African catfish Clarias gariepinus: Hormonal, enzymatic and antioxidant responses. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2014; 106:33-39. [PMID: 24836875 DOI: 10.1016/j.ecoenv.2014.04.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2014] [Revised: 04/20/2014] [Accepted: 04/21/2014] [Indexed: 06/03/2023]
Abstract
The present study examined the impacts of carbofuran on endocrinology of the catfish, Clarias gariepinus, for the first time and evaluated cortisol (CRT), triiodothyronine (T3), thyroxin (T4), 17β-estradiol (E2) and testosterone (TST) and the oxidative stress markers including SOD, CAT, GSTs, GSH. The toxic effects on the metabolic enzymes, G6PDH and LDH, in addition to lipid peroxidation (LPO) and DNA damage as biomarkers in Nile catfish, to sublethal exposures of carbofuran (0.16 and 0.49mg/L, for 35 days) were studied. Statistically significant differences between selected parameters between control and carbofuran-treated fish were recorded. Carbofuran caused a significant (p<0.05) increase in CRT and T3 levels; the mean levels of T4, TST, E2 exhibited significant decreases (p<0.05) in carbofuran-treated fish. Toxicity of carbofuran on liver, kidney, gills, gonads and muscles after 35 days of exposure was found. Glycogen levels showed a highly significant decrease in liver and gills (p< 0.001), a significant decrease (p< 0.05) in kidney and muscles, and insignificant changes (p>0.05) in gonads of treated fish. The two metabolic enzymes G6PDH and LDH in all tissues exhibited significant decreases (p<0.05) in treated fish. SOD, CAT, GSH and GST levels showed significant decreases (p<0.05) in all tissues of fish after exposure to carbofuran. LPO levels increased significantly (p<0.05) in all tissues except gonads after 5 weeks of exposure to carbofuran. There was a significant (p<0.05) increase in DNA fragmentation percentage in treated fish. Our results provide a clear evidence on the response of C. gariepinus to sublethal doses of carbofuran and allow us to consider catfish as a good bioindicator to reflect the endocrine disrupting impacts of carbofuran, and reflect the potential of this pesticide to cause disturbance in antioxidant defense system as well as metabolism and induction of lipid peroxidation (LPO) and DNA damage in contaminated ecosystems.
Collapse
Affiliation(s)
- Ahmed Th A Ibrahim
- Zoology Department, Faculty of Science, New Valley Branch, Assiut University, Assiut, Egypt.
| | - Ahmed S A Harabawy
- Zoology Department, Faculty of Science, Assiut University, Assiut, Egypt; Biology Department, Faculty of Science, North Jeddah, King Abdulaziz University, Jeddah, Saudi Arabia
| |
Collapse
|
|
20
|
Lasram MM, Bouzid K, Douib IB, Annabi A, El Elj N, El Fazaa S, Abdelmoula J, Gharbi N. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat. Drug Chem Toxicol 2014; 38:227-34. [DOI: 10.3109/01480545.2014.933348] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
|
|
21
|
Budin SB, Han CM, Jayusman PA, Taib IS. Tocotrienol rich fraction prevents fenitrothion induced pancreatic damage by restoring antioxidant status. Pak J Biol Sci 2013; 15:517-23. [PMID: 24191625 DOI: 10.3923/pjbs.2012.517.523] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Fenitrothion (FNT) is extensively used as pesticide and may induce oxidative stress in various organs. Tocotrienol, a form of vitamin E found in palm oil, reduces oxidative impairments in pathological conditions. This study aims to investigate the effects of palm oil tocotrienol rich fraction (TRF) on fenitrothion-induced oxidative damage in rat pancreas. Forty male Sprague-Dawley rats were divided into four groups: control group, FNT group, TRF group and FNT+TRF group. Regimens FNT (20 mg kg(-1) b.wt.) and TRF (200 mg kg(-1) b.wt.) were force-fed for 28 consecutive days with control group only receiving corn oil. Chronic administration of fenitrothion significantly (p < 0.05) induced oxidative damage in pancreas of rats with elevated malondialdehyde and protein carbonyl level. Depletion of glutathione and significant (p < 0.05) reduction in antioxidant enzyme activities in pancreas homogenate additionally suggested induction of oxidative stress. Despite these changes in pancreas of intoxicated rats, no significant (p < 0.05) changes in blood glucose and pancreas histology were observed. Co-administration of FNT with TRF alleviated these oxidative changes and significantly (p < 0.05) restored antioxidant status. Enzymatic activities of Superoxide Dismutase (SOD) and Catalase (CAT) were normalized. In conclusion, tocotrienol rich fraction of palm oil prevents fenitrothion-induced pancreatic oxidative damage in rats.
Collapse
Affiliation(s)
- Siti Balkis Budin
- Department of Biomedical Science, School of Diagnostic and Applied Health Sciences, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia
| | | | | | | |
Collapse
|
|
22
|
Tuzcu K, Alp H, Ozgur T, Karcioglu M, Davarci I, Evliyaoglu O, Karakus A, Hakimoglu S. Oral intralipid emulsion use: a novel therapeutic approach to pancreatic β-cell injury caused by malathion toxicity in rats. Drug Chem Toxicol 2013; 37:261-7. [DOI: 10.3109/01480545.2013.838780] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
|
|
23
|
Elsharkawy EE, Yahia D, El-Nisr NA. Sub-chronic exposure to chlorpyrifos induces hematological, metabolic disorders and oxidative stress in rat: attenuation by glutathione. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2013; 35:218-227. [PMID: 23333651 DOI: 10.1016/j.etap.2012.12.009] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/15/2012] [Revised: 12/08/2012] [Accepted: 12/19/2012] [Indexed: 06/01/2023]
Abstract
The current work aimed to investigate the different toxic effects of chlorpyrifos (CPF) in subchronic exposure. Two groups of Sprague-Dawley male rats were exposed to CPF alone in a dose of 30 mg/kg body weight, or CPF dose as previous plus glutathione (GSH) in a dose of 100 mg/kg body weight, for 90 days, twice weekly, orally. Another two groups of rat were given corn oil (control) or GSH. There is a significant decrease in hemoglobin concentration, haematocrit percentage, thrombocytic indices, total protein and albumin levels in CPF-exposed group. CPF induced hyperglycemia and significant increase in total cholesterol, but a significant decrease in triglyceride levels was obtained. A significant increase in the levels of lipid peroxidation was obtained while a significant decrease of the total antioxidant was recorded. The decrease in glycogen content and some histopathological changes were observed in liver after CPF exposure. Furthermore, co-administration of GSH can restore some of these alterations.
Collapse
Affiliation(s)
- Eman E Elsharkawy
- Department of Forensic Medicine and Toxicology Faculty of Veterinary Medicine, Assuit University, Egypt.
| | | | | |
Collapse
|
|
24
|
Nurulain SM, Petroianu G, Shafiullah M, Kalász H, Oz M, Saeed T, Adem A, Adeghate E. Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat. J Appl Toxicol 2012; 33:1036-43. [PMID: 22886793 DOI: 10.1002/jat.2794] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2012] [Revised: 06/01/2012] [Accepted: 06/02/2012] [Indexed: 02/05/2023]
Abstract
There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure.
Collapse
Affiliation(s)
- Syed M Nurulain
- Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, United Arab Emirates University, UAE
| | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Amaral TS, Carvalho TF, Silva MC, Goulart LS, Barros MS, Picanço MC, Neves CA, Freitas MB. Metabolic and Histopathological Alterations in the Fruit-Eating BatArtibeus lituratusInduced by the Organophosphorous Pesticide Fenthion. ACTA CHIROPTEROLOGICA 2012. [DOI: 10.3161/150811012x654420] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|
|
26
|
Mostafalou S, Eghbal MA, Nili-Ahmadabadi A, Baeeri M, Abdollahi M. Biochemical evidence on the potential role of organophosphates in hepatic glucose metabolism toward insulin resistance through inflammatory signaling and free radical pathways. Toxicol Ind Health 2011; 28:840-51. [DOI: 10.1177/0748233711425073] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Several studies show that organophosphate pesticides exert several effects on glucose homeostasis. The current study investigates the influence of subchronic exposure to malathion (MT) on hepatic gluconeogenesis in relation to acetyl cholinesterase (AChE) inhibition, oxidative stress and inflammatory response in the rat. MT was administered by gavage at doses of 25, 50 and 100 mg/kg for 32 days. Fasting hyperglycemia was seen in line with an increased activity of hepatic phosphoenolpyruvate carboxykinase, glucose 6-phosphatase and tumor necrosis factor α. In addition to the impaired glucose tolerance and inhibition of AChE in a dose-dependent manner, there were significant increases in hepatic lipid peroxidation, carbonyl groups and 8-deoxyguanosine as the biomarkers of reactive oxygen species–mediated damage to lipid, protein and DNA, respectively. Altered quality of the liver in glucose production especially gluconeogenesis could be a compensatory mechanism against MT toxicity or even result in tissue damage. MT-induced insulin resistance in the liver occurs through oxidative and inflammatory signaling pathways.
Collapse
Affiliation(s)
- Sara Mostafalou
- Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Ali Eghbal
- Department of Pharmacology and Toxicology, Tabriz University of Medical Sciences, Tabriz, Iran
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Amir Nili-Ahmadabadi
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Maryam Baeeri
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
- Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
27
|
Uboh F, Asuquo E, Eteng M, Akpanyung E. Endosulfan-Induces Renal Toxicity Independent of the Route of Exposure in Rats. ACTA ACUST UNITED AC 2011. [DOI: 10.3923/ajbmb.2011.359.367] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
|
|
28
|
Karami-Mohajeri S, Abdollahi M. Toxic influence of organophosphate, carbamate, and organochlorine pesticides on cellular metabolism of lipids, proteins, and carbohydrates: a systematic review. Hum Exp Toxicol 2010; 30:1119-40. [PMID: 21071550 DOI: 10.1177/0960327110388959] [Citation(s) in RCA: 276] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Pesticides, including organophosphate (OP), organochlorine (OC), and carbamate (CB) compounds, are widely used in agricultural and indoor purposes. OP and CB act as acetyl cholinesterase (AChE) inhibitors that affect lots of organs such as peripheral and central nervous systems, muscles, liver, pancreas, and brain, whereas OC are neurotoxic involved in alteration of ion channels. There are several reports about metabolic disorders, hyperglycemia, and also oxidative stress in acute and chronic exposures to pesticides that are linked with diabetes and other metabolic disorders. In this respect, there are several in vitro and in vivo but few clinical studies about mechanism underlying these effects. Bibliographic databases were searched for the years 1963-2010 and resulted in 1652 articles. After elimination of duplicates or irrelevant papers, 204 papers were included and reviewed. Results indicated that OP and CB impair the enzymatic pathways involved in metabolism of carbohydrates, fats and protein within cytoplasm, mitochondria, and proxisomes. It is believed that OP and CB show this effect through inhibition of AChE or affecting target organs directly. OC mostly affect lipid metabolism in the adipose tissues and change glucose pathway in other cells. As a shared mechanism, all OP, CB and OC induce cellular oxidative stress via affecting mitochondrial function and therefore disrupt neuronal and hormonal status of the body. Establishing proper epidemiological studies to explore exact relationships between exposure levels to these pesticides and rate of resulted metabolic disorders in human will be helpful.
Collapse
Affiliation(s)
- Somayyeh Karami-Mohajeri
- Faculty of Pharmacy, and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | | |
Collapse
|
|
29
|
Rezg R, Mornagui B, Benahmed M, Gharsalla Chouchane S, Belhajhmida N, Abdeladhim M, Kamoun A, El-fazaa S, Gharbi N. Malathion exposure modulates hypothalamic gene expression and induces dyslipedemia in Wistar rats. Food Chem Toxicol 2010; 48:1473-7. [DOI: 10.1016/j.fct.2010.03.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2009] [Revised: 02/26/2010] [Accepted: 03/10/2010] [Indexed: 10/19/2022]
|
|
30
|
Physiological and histopathological investigations on the effects of alpha-lipoic acid in rats exposed to malathion. J Biomed Biotechnol 2010; 2010:203503. [PMID: 20454535 PMCID: PMC2864892 DOI: 10.1155/2010/203503] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2010] [Accepted: 03/07/2010] [Indexed: 11/20/2022] Open
Abstract
The present study was designed to evaluate the influence of α-lipoic acid treatment in rats exposed to malathion. Forty adult male rats were used in this study and distributed into four groups. Animals of group 1 were untreated and served as control. Rats of group 2 were orally given malathion at a dose level of 100 mg/kg body weight (BW) for a period of one month. Experimental animals of group 3 were orally given α-lipoic acid at a dose level of 20 mg/kg BW and after 3 hours exposed to malathion at the same dose given to group 2. Rats of group 4 were supplemented with α-lipoic acid at the same dose given to group 3. The activities of serum glutamic oxaloacetic acid transaminase (GOT), glutamic pyruvic acid transaminase (GPT), alkaline phosphatase (ALP), and acid phosphatase (ACP), and the values of creatinine, urea, and uric acid were statistically increased, while the values of total protein and total albumin were significantly decreased in rats exposed to malathion. Moreover, administration of malathion for one month resulted in damage of liver and kidney structures. Administration of α-lipoic acid before malathion exposure to rat can prevent severe alterations of hematobiochemical parameters and disruptions of liver and kidney structures. In conclusion, this study obviously demonstrated that pretreatment with α-lipoic acid significantly attenuated the physiological and histopathological alterations induced by malathion. Also, the present study identifies new areas of research for development of better therapeutic agents for liver, kidney, and other organs' dysfunctions and diseases.
Collapse
|
|
31
|
Floettmann E, Gregory L, Teague J, Myatt J, Hammond C, Poucher SM, Jones HB. Prolonged Inhibition of Glycogen Phosphorylase in Livers of Zucker Diabetic Fatty Rats Models Human Glycogen Storage Diseases. Toxicol Pathol 2010; 38:393-401. [DOI: 10.1177/0192623310362707] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
The preclinical efficacy and safety of GPi921, a glycogen phosphorylase inhibitor, was assessed following twenty-eight days of administration to Zucker Diabetic Fatty (ZDF) rats. The ZDF rat is an animal model of type 2 diabetes mellitus (TTDM) which develops severe hyperglycemia. Inhibition of glycogen phosphorylase throughout the duration of the study was demonstrated by reductions in twenty-four-hour glucose profiles and glycated hemoglobin levels. In addition, progression towards hyperglycemia was halted in treated but not control animals, which developed hyperglycemia over the twenty-eight days of the study. Biochemical and histopathological analysis revealed large increases in hepatic glycogen, which closely paralleled the development of hepatomegaly and ultimately resulted in increases in hepatic lipids. Furthermore, prolonged glycogen phosphorylase inhibition resulted in an increased incidence and severity of other adverse pathological findings in the liver, such as inflammation, fibrosis, hemorrhage, and necrosis. The observed biochemical and histopathological phenotype of the liver closely resembled that seen in severe cases of human glycogen storage diseases (GSD) and hepatic glycogenosis in poorly controlled diabetes mellitus. These findings revealed that although glycogen phosphorylase inhibitors are efficacious agents for the control of hyperglycemia, prolonged treatment might have the potential to cause significant clinical hepatic complications that resemble those seen in GSD and hepatic glycogenosis.
Collapse
Affiliation(s)
- Eike Floettmann
- Global Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - Laraine Gregory
- Cardiovascular & Gastrointestinal Research Department, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - Joanne Teague
- Cardiovascular & Gastrointestinal Research Department, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - John Myatt
- Global Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - Clare Hammond
- Drug Metabolism and Pharmacokinetics, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - Simon M. Poucher
- Cardiovascular & Gastrointestinal Research Department, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| | - Huw B. Jones
- Global Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, United Kingdom
| |
Collapse
|
|
32
|
Comparative Effects of Calcium Channel Blockers, Autonomic Nervous System Blockers, and Free Radical Scavengers On Diazinon-Induced Hyposecretion Of Insulin From Isolated Islets of Langerhans in Rats. Arh Hig Rada Toksikol 2009; 60:157-64. [DOI: 10.2478/10004-1254-60-2009-1917] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Comparative Effects of Calcium Channel Blockers, Autonomic Nervous System Blockers, and Free Radical Scavengers On Diazinon-Induced Hyposecretion Of Insulin From Isolated Islets of Langerhans in RatsHyperglycaemia has been observed with exposure to organophosphate insecticides. This study was designed to compare the effects of calcium channel blockers, alpha-adrenergic, beta-adrenergic, and muscarinic receptor blockers, and of free radical scavengers on insulin secretion from diazinon-treated islets of Langerhans isolated from the pancreas of rats using standard collagenase digestion, separation by centrifugation, and hand-picking technique. The islets were then cultured in an incubator at 37 °C and 5 % CO2. In each experimental set 1 mL of 8 mmol L-1 glucose plus 125 μg mL-1 or 625 μg mL-1 of diazinon were added, except for the control group, which received 8 mmol L-1 glucose alone. The cultures were then treated with one of the following: 30 μmol L-1 atropine, 100 μmol L-1 ACh + 10 μmol L-1 neostigmine, 0.1 μmol L-1 propranolol, 2 μmol L-1 nifedipine, 50 μmol L-1 phenoxybenzamine, or 10 μmol L-1 alphatocopherol. In all experiments, diazinon significantly reduced glucose-stimulated insulin secretion at both doses, showing no dose dependency, as the average inhibition for the lower dose was 62.20 % and for the higher dose 64.38 %. Acetylcholine and alpha-tocopherol restored, whereas atropine potentiated diazinon-induced hyposecretion of insulin. Alpha-, beta- and calcium channel blockers did not change diazinon-induced effects. These findings suggest that diazinon affects insulin secretion mainly by disturbing the balance between free radicals and antioxidants in the islets of Langerhans and by inducing toxic stress.
Collapse
|
|
33
|
Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: Effect on superoxide dismutase and catalase activities using native PAGE. C R Biol 2008; 331:655-62. [DOI: 10.1016/j.crvi.2008.06.004] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2008] [Revised: 05/01/2008] [Accepted: 06/11/2008] [Indexed: 11/23/2022]
|
|
34
|
Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Caffeic acid attenuates malathion induced metabolic disruption in rat liver, involvement of acetylcholinesterase activity. Toxicology 2008; 250:27-31. [DOI: 10.1016/j.tox.2008.05.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2008] [Revised: 05/20/2008] [Accepted: 05/21/2008] [Indexed: 12/19/2022]
|
|
35
|
Sadeghi-Hashjin G, Moslemi M, Javadi S. The effect of organophosphate pesticides on the blood glucose levels in the mouse. Pak J Biol Sci 2008; 11:1290-1292. [PMID: 18819542 DOI: 10.3923/pjbs.2008.1290.1292] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/26/2023]
Abstract
The aim of the present study was to study the effect of two selected agents of this group on blood glucose levels in an animal model. Forty-two adult male mice were divided into 7 groups of 6 each. Animals were exposed by their entire tail for 10 sec once a day for 7 successive days to either 0, 0.1, 1, or 10% azynphos methyl (AZP) malathion (MLT). On days 1,4 and 8, a small drop of blood was taken from tail of the animals that had been kept fasted overnight. Blood glucose levels were measure using a glucometer. The animals then were fed and after 1 h the blood glucose measurement was performed again. Results of this study indicated that the administration of organophosphate agents significantly prevented from the rise of blood glucose after feeding in comparison to the control animals. This reached the level of statistical significance on day 1 with MLT 1% (p < 0.001). It is concluded that exposure with organophosphate pesticides may suppress excessive blood glucose levels with no effect on the basal blood glucose in the fasting animals.
Collapse
|
|
36
|
Rezg R, Mornagui B, Kamoun A, El-Fazaa S, Gharbi N. Effect of subchronic exposure to malathion on metabolic parameters in the rat. C R Biol 2007; 330:143-7. [PMID: 17303541 DOI: 10.1016/j.crvi.2006.11.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2006] [Revised: 11/09/2006] [Accepted: 11/14/2006] [Indexed: 10/23/2022]
Abstract
This study investigates the effects of subchronic exposure to organophosphate insecticide Malathion (Fyfanon 50 EC 500 g/l) of commercial grade. It was administered intragastrically by stomach tube in the amount of 1 ml of corn oil containing 100 mg/kg body weight (BW) daily for 32 days. At the end of the experiment, acetylcholinesterase activity (AChE), haematocrit value, haemoglobin content, and blood glucose concentration were estimated. The liver and the skeletal muscle were removed to determine hepatic and muscular glycogen, hepatic proteins and lipids contents. No sign of toxicity was observed until the end of experiment. No significant change in the haematocrit value was observed, in spite of the significant increase in haemoglobin content, which can be considered as an adaptive situation in order to guarantee a good oxygenation in response to pulmonary damage induced following subchronic exposure to organophosphorus compound. Malathion intoxication decreased significantly hepatic proteins and lipid contents that could be associated to liver gluconeogenesis. This result was coupled with a significant decrease in muscular glycogen rate, which indicates a stimulated glycogenolysis in favour of glucose release into the blood until reaching hyperglycaemia. Several studies indicate that hyperglycaemia is temporary, which is probably due to a stimulated glycogenesis that increases hepatic glycogen deposition and return of glucose to control levels, as demonstrated in our study. One possible explanation for these results could be the turnover of glucose by a succession between its release via glycogenolysis and gluconeogenesis, which involves abnormal hyperglycaemia, and its storage via glycogenesis in subchronic exposure to malation.
Collapse
Affiliation(s)
- Raja Rezg
- Laboratoire de Physiologie des Agressions, Département de Biologie, Faculté des Sciences de Tunis, Campus Universitaire, 2092 Manar II, Tunis, Tunisie.
| | | | | | | | | |
Collapse
|