|
1
|
Wang J, Miao Z, Gao Y, Xie Z, Liu M, Zou W. Formyl peptide receptor 2: a potential therapeutic target for inflammation-related diseases. Pharmacol Rep 2025; 77:593-609. [PMID: 40102363 DOI: 10.1007/s43440-025-00704-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2024] [Revised: 01/23/2025] [Accepted: 01/23/2025] [Indexed: 03/20/2025]
Abstract
Formyl peptide receptor 2 (FPR2) is a G protein-coupled receptor with seven transmembrane domains, widely distributed in human cells. It plays a crucial role in inflammation-related diseases. Known for its "double-edged sword" nature, FPR2 can bind a variety of exogenous and endogenous ligands, mediating both pro-inflammatory and anti-inflammatory responses in tissues such as eyes, liver, joints, lungs, nerves, and blood vessels. FPR2's bioactivities are regulated by a complex network of genes and signaling pathways. However, the precise regulatory mechanisms governing its functions in different inflammatory conditions are still not well understood. This review summarizes the FPR2's activities in various inflammation-related diseases and looks into its potential as a therapeutic target. This review highlights recent advances in developing exogenous agonists for FPR2 and discusses receptor expression across species to support nonclinical research. Overall, this review aims to clarify FPR2's role in inflammation and provide insights for the development of new drugs against inflammatory diseases.
Collapse
Affiliation(s)
- Jiaying Wang
- School of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, University of South China, Hengyang, 421001, China
| | - Zhishuo Miao
- Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - Yinhuang Gao
- Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China
| | - ZhiZhong Xie
- School of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, University of South China, Hengyang, 421001, China
| | - Menghua Liu
- Key Laboratory of Drug Metabolism Research and Evaluation of the State Drug Administration, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China.
| | - Wei Zou
- School of Pharmacy, Hunan Provincial Maternal and Child Health Care Hospital, University of South China, Hengyang, 421001, China.
| |
Collapse
|
|
2
|
Sastre J, Pérez S, Sabater L, Rius-Pérez S. Redox signaling in the pancreas in health and disease. Physiol Rev 2025; 105:593-650. [PMID: 39324871 DOI: 10.1152/physrev.00044.2023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 09/11/2024] [Accepted: 09/17/2024] [Indexed: 09/27/2024] Open
Abstract
This review addresses oxidative stress and redox signaling in the pancreas under healthy physiological conditions as well as in acute pancreatitis, chronic pancreatitis, pancreatic cancer, and diabetes. Physiological redox homeodynamics is maintained mainly by NRF2/KEAP1, NF-κB, protein tyrosine phosphatases, peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), and normal autophagy. Depletion of reduced glutathione (GSH) in the pancreas is a hallmark of acute pancreatitis and is initially accompanied by disulfide stress, which is characterized by protein cysteinylation without increased glutathione oxidation. A cross talk between oxidative stress, MAPKs, and NF-κB amplifies the inflammatory cascade, with PP2A and PGC1α as key redox regulatory nodes. In acute pancreatitis, nitration of cystathionine-β synthase causes blockade of the transsulfuration pathway leading to increased homocysteine levels, whereas p53 triggers necroptosis in the pancreas through downregulation of sulfiredoxin, PGC1α, and peroxiredoxin 3. Chronic pancreatitis exhibits oxidative distress mediated by NADPH oxidase 1 and/or CYP2E1, which promotes cell death, fibrosis, and inflammation. Oxidative stress cooperates with mutant KRAS to initiate and promote pancreatic adenocarcinoma. Mutant KRAS increases mitochondrial reactive oxygen species (ROS), which trigger acinar-to-ductal metaplasia and progression to pancreatic intraepithelial neoplasia (PanIN). ROS are maintained at a sufficient level to promote cell proliferation, while avoiding cell death or senescence through formation of NADPH and GSH and activation of NRF2, HIF-1/2α, and CREB. Redox signaling also plays a fundamental role in differentiation, proliferation, and insulin secretion of β-cells. However, ROS overproduction promotes β-cell dysfunction and apoptosis in type 1 and type 2 diabetes.
Collapse
Affiliation(s)
- Juan Sastre
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Salvador Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
| | - Luis Sabater
- Liver, Biliary and Pancreatic Unit, Hospital Clínico, Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain
| | - Sergio Rius-Pérez
- Department of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain
- Department of Cell Biology, Functional Biology and Physical Anthropology, Faculty of Biology, University of Valencia, Valencia, Spain
| |
Collapse
|
|
3
|
Feng Y, Chen X, Chen D, He J, Zheng P, Luo Y, Yu B, Huang Z. Dietary grape seed proanthocyanidin extract supplementation improves antioxidant capacity and lipid metabolism in finishing pigs. Anim Biotechnol 2023; 34:4021-4031. [PMID: 37647084 DOI: 10.1080/10495398.2023.2252012] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/01/2023]
Abstract
Grape seed proanthocyanidin extract (GSPE) plays a significant role in body health, including improving antioxidant capacity and maintaining lipid metabolism stability. However, whether dietary GSPE supplementation can improve lipid metabolism in finishing pigs remains unclear. Here 18 castrated male Duroc × Landrace × Yorkshire finishing pigs were randomly divided into three groups with six replicates and one pig per replicate. Pigs were fed a basal diet (control), a basal diet supplemented with 100 mg/kg GSPE, or a basal diet supplemented with 200 mg/kg GSPE for 30 days. Antioxidant analysis showed that dietary 200 mg/kg GSPE supplementation increased glutathione, total antioxidant capacity and glutathione peroxidase levels, and reduced malondialdehyde levels in serum, muscle and liver. Dietary 200 mg/kg GSPE supplementation also upregulated the mRNA and protein levels of nuclear-related factor 2 (Nrf2). Lipid metabolism analysis showed that dietary GSPE supplementation increased serum high-density lipoprotein cholesterol levels and reduced serum triglyceride and total cholesterol levels. Besides, GPSE upregulated the mRNA expression of lipolysis- and fatty acid oxidation-related genes downregulated the mRNA expression of lipogenesis-related genes, and activated the AMPK signal in finishing pigs. Together, we provided evidence that dietary GSPE supplementation improved the antioxidant capacity and lipid metabolism in finishing pigs.
Collapse
Affiliation(s)
- Yadi Feng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Xiaoling Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Daiwen Chen
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Jun He
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Ping Zheng
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Yuheng Luo
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Bing Yu
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| | - Zhiqing Huang
- Key Laboratory for Animal Disease-Resistance Nutrition of China Ministry of Education, Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu, Sichuan, P. R. China
| |
Collapse
|
|
4
|
Effect of chlorogenic acid on lipid metabolism in 3T3-L1 cells induced by oxidative stress. FOOD BIOSCI 2022. [DOI: 10.1016/j.fbio.2022.102330] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
|
|
5
|
Yao J, Miao Y, Zhang Y, Zhu L, Chen H, Wu X, Yang Y, Dai X, Hu Q, Wan M, Tang W. Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries via Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats. Front Pharmacol 2022; 13:922130. [PMID: 35899121 PMCID: PMC9310041 DOI: 10.3389/fphar.2022.922130] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 06/20/2022] [Indexed: 11/17/2022] Open
Abstract
Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries via inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.
Collapse
Affiliation(s)
- Jiaqi Yao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yifan Miao
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yumei Zhang
- Department of Traditional Chinese Medicine, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China
| | - Lv Zhu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Huan Chen
- Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, China
| | - Xiajia Wu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Yue Yang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Xiaoyu Dai
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Qian Hu
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Meihua Wan
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Wenfu Tang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Wenfu Tang,
| |
Collapse
|
|
6
|
Liu D, Wen L, Wang Z, Hai Y, Yang D, Zhang Y, Bai M, Song B, Wang Y. The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review. Front Med (Lausanne) 2022; 9:904078. [PMID: 35872761 PMCID: PMC9301017 DOI: 10.3389/fmed.2022.904078] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 05/10/2022] [Indexed: 12/12/2022] Open
Abstract
Acute pancreatitis (AP), as a common cause of clinical acute abdomen, often leads to multi-organ damage. In the process of severe AP, the lungs and intestines are the most easily affected organs aside the pancreas. These organ damages occur in succession. Notably, lung and intestinal injuries are closely linked. Damage to ML, which transports immune cells, intestinal fluid, chyle, and toxic components (including toxins, trypsin, and activated cytokines to the systemic circulation in AP) may be connected to AP. This process can lead to the pathological changes of hyperosmotic edema of the lung, an increase in alveolar fluid level, destruction of the intestinal mucosal structure, and impairment of intestinal mucosal permeability. The underlying mechanisms of the correlation between lung and intestinal injuries are inflammatory response, oxidative stress, and endocrine hormone secretion disorders. The main signaling pathways of lung and intestinal injuries are TNF-α, HMGB1-mediated inflammation amplification effect of NF-κB signal pathway, Nrf2/ARE oxidative stress response signaling pathway, and IL-6-mediated JAK2/STAT3 signaling pathway. These pathways exert anti-inflammatory response and anti-oxidative stress, inhibit cell proliferation, and promote apoptosis. The interaction is consistent with the traditional Chinese medicine theory of the lung being connected with the large intestine (fei yu da chang xiang biao li in Chinese). This review sought to explore intersecting mechanisms of lung and intestinal injuries in AP to develop new treatment strategies.
Collapse
Affiliation(s)
- Dongling Liu
- School of Pharmacy, Gansu University of Chinese Medicine, Lanzhou, China
| | - Linlin Wen
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
- County People’s Hospital, Pingliang, China
| | - Zhandong Wang
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yang Hai
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
| | - Dan Yang
- School of Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Yanying Zhang
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Min Bai
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Bing Song
- Gansu University of Chinese Medicine/Scientific Research and Experimental Center, Lanzhou, China
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| | - Yongfeng Wang
- Gansu Provincial Engineering Laboratory for Research and Promotion of Quality Standardization of Authentic Medicinal Materials in Gansu Province/Provincial Key Laboratory of Pharmaceutical Chemistry and Quality Research in Colleges and Universities in Gansu Province/Gansu Provincial Laboratory Animal Industry Technology Center, Lanzhou, China
| |
Collapse
|
|
7
|
Zou F, Zhuang ZB, Zou SS, Wang B, Zhang ZH. BML-111 alleviates inflammatory response of alveolar epithelial cells via miR-494/Slit2/Robo4 signalling axis to improve acute lung injury. Autoimmunity 2022; 55:318-327. [PMID: 35656971 DOI: 10.1080/08916934.2022.2065671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Affiliation(s)
- Fang Zou
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, P.R. China
| | - Zhong-Bao Zhuang
- Department of Pharmacy, Hebei North University, Zhangjiakou, Hebei Province, P.R. China
| | - Shuang-Shuang Zou
- Guangzhou Liwan Stomatological Hospital, Guangzhou, Guangdong Province, P.R. China
| | - Bu Wang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, P.R. China
| | - Zhi-Hua Zhang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Hebei North University, Zhangjiakou, Hebei Province, P.R. China
| |
Collapse
|
|
8
|
Sun H, Wang J, Bi W, Zhang F, Chi K, Shi L, Yuan T, Ma K, Gao X. Sulforaphane Ameliorates Limb Ischemia/Reperfusion-Induced Muscular Injury in Mice by Inhibiting Pyroptosis and Autophagy via the Nrf2-ARE Pathway. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:4653864. [PMID: 35600947 PMCID: PMC9117032 DOI: 10.1155/2022/4653864] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 04/19/2022] [Accepted: 04/22/2022] [Indexed: 11/17/2022]
Abstract
Background Limb ischemia/reperfusion (I/R) injury, as a life-threatening syndrome, is commonly caused by skeletal muscle damage resulting from oxidative stress. Additionally, inflammation-induced pyroptosis and dysregulated autophagy are vital factors contributing to the aggravation of I/R injury. Of note, sulforaphane (SFN) is a natural antioxidant, but whether it worked in limb I/R injury and the possible mechanism behind its protection for skeletal muscle has not been clearly established. Methods Effects of SFN on limb I/R-injured skeletal muscle were assessed by HE staining, followed by assessment of wet weight/dry weight (W/D) ratio of muscle tissues. Next, ELISA and biochemical tests were used to measure the inflammatory cytokine production and oxidative stress. Immunofluorescent analysis and Western blot were adopted to examine the level of pyroptosis- and autophagy-related proteins in vivo. Moreover, protein levels of Nrf2-ARE pathway-related factors were also examined using Western blot. Results SFN treatment could protect skeletal muscle against limb I/R injury, as evidenced by diminished inflammation, pyroptosis, autophagy, and oxidative stress in skeletal muscles of mice. Further mechanistic exploration confirmed that antioxidative protection of SFN was associated with the Nrf2-ARE pathway activation. Conclusions SFN activates the Nrf2-ARE pathway, and thereby inhibits pyroptosis and autophagy and provides a novel therapeutic strategy for the limb I/R-induced muscle tissue damage.
Collapse
Affiliation(s)
- Huanhuan Sun
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Jueqiong Wang
- Department of Neurology, Neurological Laboratory of Hebei Province, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Wei Bi
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Feng Zhang
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Kui Chi
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Long Shi
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Tao Yuan
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Kai Ma
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| | - Xiang Gao
- Department of Vascular Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei, China
| |
Collapse
|
|
9
|
Formyl peptide receptor 2, as an important target for ligands triggering the inflammatory response regulation: a link to brain pathology. Pharmacol Rep 2021; 73:1004-1019. [PMID: 34105114 PMCID: PMC8413167 DOI: 10.1007/s43440-021-00271-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 04/13/2021] [Accepted: 04/30/2021] [Indexed: 12/28/2022]
Abstract
Formyl peptide receptors (FPRs) belong to the family of seven-transmembrane G protein-coupled receptors. Among them, FPR2 is a low affinity receptor for N-formyl peptides and is considered the most promiscuous member of FPRs. FPR2 is able to recognize a broad variety of endogenous or exogenous ligands, ranging from lipid to proteins and peptides, including non-formylated peptides. Due to this property FPR2 has the ability to modulate both pro- and anti-inflammatory response, depending on the nature of the bound agonist and on the different recognition sites of the receptor. Thus, FPR2 takes part not only in the proinflammatory response but also in the resolution of inflammation (RoI) processes. Recent data have indicated that the malfunction of RoI may be the background for some central nervous system (CNS) disorders. Therefore, much interest is focused on endogenous molecules called specialized pro-resolving mediators (SPMs), as well as on new synthetic FPR2 agonists, which kick-start the resolution of inflammation (RoI) and modulate its course. Here, we shed some light on the general characteristics of the FPR family in humans and in the experimental animals. Moreover, we present a guide to understanding the "double faced" action of FPR2 activation in the context of immune-related diseases of the CNS.
Collapse
|
|
10
|
Regulska M, Szuster-Głuszczak M, Trojan E, Leśkiewicz M, Basta-Kaim A. The Emerging Role of the Double-Edged Impact of Arachidonic Acid- Derived Eicosanoids in the Neuroinflammatory Background of Depression. Curr Neuropharmacol 2020; 19:278-293. [PMID: 32851950 PMCID: PMC8033972 DOI: 10.2174/1570159x18666200807144530] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 06/18/2020] [Accepted: 07/31/2020] [Indexed: 12/14/2022] Open
Abstract
Eicosanoids are arachidonic acid (AA) derivatives belonging to a family of lipid signalling mediators that are engaged in both physiological and pathological processes in the brain. Recently, their implication in the prolonged inflammatory response has become a focus of particular interest because, in contrast to acute inflammation, chronic inflammatory processes within the central nervous system (CNS) are crucial for the development of brain pathologies including depression. The synthesis of eicosanoids is catalysed primarily by cyclooxygenases (COX), which are involved in the production of pro-inflammatory AA metabolites, including prostaglandins and thromboxanes. Moreover, eicosanoid synthesis is catalysed by lipoxygenases (LOXs), which generate both leukotrienes and anti-inflammatory derivatives such as lipoxins. Thus, AA metabolites have double- edged pro-inflammatory and anti-inflammatory, pro-resolving properties, and an imbalance between these metabolites has been proposed as a contributor or even the basis for chronic neuroinflammatory effects. This review focuses on important evidence regarding eicosanoid-related pathways (with special emphasis on prostaglandins and lipoxins) that has added a new layer of complexity to the idea of targeting the double-edged AA-derivative pathways for therapeutic benefits in depression. We also sought to explore future research directions that can support a pro-resolving response to control the balance between eicosanoids and thus to reduce the chronic neuroinflammation that underlies at least a portion of depressive disorders.
Collapse
Affiliation(s)
- Magdalena Regulska
- Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland
| | - Magdalena Szuster-Głuszczak
- Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland
| | - Ewa Trojan
- Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland
| | - Monika Leśkiewicz
- Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland
| | - Agnieszka Basta-Kaim
- Immunoendocrinology Laboratory, Department of Experimental Neuroendocrinology, Maj Institute of Pharmacology, Polish Academy of Sciences, 12 Smętna St, 31-343 Krakow, Poland
| |
Collapse
|
|
11
|
Liang X, Hu C, Liu C, Yu K, Zhang J, Jia Y. Dihydrokaempferol (DHK) ameliorates severe acute pancreatitis (SAP) via Keap1/Nrf2 pathway. Life Sci 2020; 261:118340. [PMID: 32860805 DOI: 10.1016/j.lfs.2020.118340] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 08/18/2020] [Accepted: 08/21/2020] [Indexed: 12/18/2022]
Abstract
Severe acute pancreatitis (SAP) is a non-bacterial inflammatory disease that clinically causes a very high rate of mortality. Dihydrokaempferol (DHK) is a natural flavonoid extracted from Bauhinia championii. Our research aimed to establish the treatment function of DHK on SAP-induced pancreas injury and delve into its potential mechanism. In this study, SAP was induced by caerulein (CER) and Lipopolysaccharide (LPS). DHK was administered orally at different doses of 20, 40, or 80 mg/kg. Results from serum amylase/lipase, pancreas hematoxylin-eosin staining technique, pancreas malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) showed the therapeutic effect of DHK in a mice SAP model. MTT revealed DHK alleviated CER + LPS induced cytotoxicity in a dose-dependent manner in the pancreatic acinar cells of mice. Next, we verified DHK suppressed the level of Keap1 and promoted transcriptional activation of nuclear Nrf2 in the presence of CER + LPS. The molecular docking study suggested that there is a potential interaction between DHK and Keap1. To further look at the role of Keap1 using in vitro and in vivo models, Keap1 overexpression adenovirus (ad-Keap1) was performed. The results revealed that ad-Keap1suppressed the nuclear translocation of Nrf2 which is enhanced by DHK, and suppressed the antioxidative functionality of DHK both in mice and cell models. Collectively, this research demonstrated that DHK bettered the SAP induced pancreas injury by regulating the Keap1/Nrf2 pathway and regulating oxidative stress injury.
Collapse
Affiliation(s)
- Xiaoqiang Liang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Cheng Hu
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Congying Liu
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Kui Yu
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Jingzhe Zhang
- Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
| | - Yiqun Jia
- Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
| |
Collapse
|
|
12
|
Ellipticine blocks synergistic effects of IL-17A and TNF-α in epithelial cells and alleviates severe acute pancreatitis-associated acute lung injury. Biochem Pharmacol 2020; 177:113992. [DOI: 10.1016/j.bcp.2020.113992] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2020] [Accepted: 04/21/2020] [Indexed: 12/11/2022]
|
|
13
|
Overexpression of Nrf2 Protects Against Lipopolysaccharide and Cerulein-Induced Pancreatitis In Vitro and In Vivo. Pancreas 2020; 49:420-428. [PMID: 32132514 DOI: 10.1097/mpa.0000000000001501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
OBJECTIVES In this study, we focused on the function of nuclear factor E2-related factor 2 (Nrf2) in acute pancreatitis (AP), which has been shown to have protective effects in gliomas, hepatocytes, and astrocytes. METHODS Acute pancreatitis cell line and animal model were induced by administration of lipopolysaccharide and cerulein into the cell supernatant or intraperitoneal injection. Oxidative stress status was evaluated by measuring the level of amylase, C-reactive protein, malondialdehyde, superoxide dismutase, and myeloperoxidase. Morphological alterations in the pancreas were evaluated by hematoxylin-eosin staining, the wet-to-dry weight ratio, and the pathology injury scores. Western blot, reverse transcription-polymerase chain reaction, and immunofluorescence staining were performed to analyze the expression of Nrf2, Heme oxygenase 1, and NAD(P)H: quinone oxidoreductase 1. RESULTS Overexpression of Nrf2 inhibits oxidative stress and inflammatory responses by inducting the expression of superoxide dismutase as well as reducing the level of amylase, malondialdehyde, and myeloperoxidase in the AR42J rat pancreatic acinar cells in AP. Importantly, overexpression of Nrf2 displayed the same protective effect in vivo. Data from an AP rat model showed that Nrf2 could relieve pancreatic damage. CONCLUSIONS These results indicated that Nrf2 has a protective role in lipopolysaccharide and cerulein-induced cytotoxicity, providing potential therapeutic strategies for the treatment of AP.
Collapse
|
|
14
|
Wu X, Pan C, Chen R, Zhang S, Zhai Y, Guo H. BML-111 attenuates high glucose-induced inflammation, oxidative stress and reduces extracellular matrix accumulation via targeting Nrf2 in rat glomerular mesangial cells. Int Immunopharmacol 2019; 79:106108. [PMID: 31881376 DOI: 10.1016/j.intimp.2019.106108] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Revised: 11/25/2019] [Accepted: 11/29/2019] [Indexed: 12/13/2022]
Abstract
Diabetic nephropathy (DN) is the most paradigmatic complication of diabetes mellitus (DM) and brings about severe social and economic burdens. BML-111 is a potent agonist of Lipoxin A4 and has shown anti-inflammatory function in many diseases. The aim of the study is to investigate the effects of BML-111 on high glucose (HG) -induced mesangial cells. HBZY-1 cells were stimulated by HG with or without BML-111. ML385 was used as an Nrf2 inhibitor. Cell proliferation was measured by CC-K 8 assay. Besides, levels of TNF-α, IL-1, IL-6 and MCP-1 were detected by corresponding ELISA kits. DCFH-DA staining and an available ROS kit were employed to determine the ROS generation. In addition, extracellular matrix (ECM) accumulation was evaluated by immunofluorescence assay and western blot analysis. The protein expressions involved in Nrf2/HO-1 and MAPK pathway were assessed by western blot assay. Results indicated that BML-111 extremely inhibited HBZY-1 cell proliferation induced by HG. Moreover, BML-111 reduced the levels of TNF-α, IL-1, IL-6 and MCP-1, declined intracellular ROS level, and attenuated expression of ECM proteins laminin, fibronectin, collagen IV and TGF-β1. In addition, BML-111 promoted the activation of Nrf2, HO-1, and NQO1, while suppressed the phosphorylation of p38 and JNK. Further, NRF2 silence reversed the inhibitory effects of BML-111 on HG-induce inflammation, oxidative stress and ECM accumulation, accelerate the MAPK signaling, and diminished the expression of Nrf2 pathway. In summary, BML-111 alleviated HG-induced injury in HBZY-1 cells by repressing inflammatory response, oxidative stress and ECM accumulation via activating Nrf2 and inhibiting MAPK pathway.
Collapse
Affiliation(s)
- Xiaoming Wu
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
| | - Congqing Pan
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China.
| | - Rui Chen
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
| | - Shuo Zhang
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
| | - Yangkui Zhai
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
| | - Hang Guo
- NHC Key Laboratory of Hormones and Development (Tianjin Medical University), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin 300134, China
| |
Collapse
|
|
15
|
Godugu C, Pasari LP, Khurana A, Anchi P, Saifi MA, Bansod SP, Annaldas S. Crocin, an active constituent of
Crocus sativus
ameliorates cerulein induced pancreatic inflammation and oxidative stress. Phytother Res 2019; 34:825-835. [DOI: 10.1002/ptr.6564] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Revised: 10/08/2019] [Accepted: 11/06/2019] [Indexed: 12/18/2022]
Affiliation(s)
- Chandraiah Godugu
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Lakshmi P. Pasari
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Amit Khurana
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Pratibha Anchi
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Mohd A. Saifi
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Sapana P. Bansod
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| | - Shivaraju Annaldas
- Department of Regulatory ToxicologyNational Institute of Pharmaceutical Education and Research Balanagar, Hyderabad Telangana India
| |
Collapse
|
|
16
|
BML-111 accelerates the resolution of inflammation by modulating the Nrf2/HO-1 and NF-κB pathways in rats with ventilator-induced lung injury. Int Immunopharmacol 2019; 69:289-298. [DOI: 10.1016/j.intimp.2019.02.005] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 01/21/2019] [Accepted: 02/04/2019] [Indexed: 02/08/2023]
|
|
17
|
Wu X, Ji K, Wang H, Zhao Y, Jia J, Gao X, Zang B. Retracted
: microRNA‐542‐5p protects against acute lung injury in mice with severe acute pancreatitis by suppressing the mitogen‐activated protein kinase signaling pathway through the negative regulation of P21‐activated kinase 1. J Cell Biochem 2018; 120:290-304. [DOI: 10.1002/jcb.27356] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2018] [Accepted: 06/22/2018] [Indexed: 12/19/2022]
Affiliation(s)
- Xing‐Mao Wu
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Kai‐Qiang Ji
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Hai‐Yuan Wang
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Yang Zhao
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Jia Jia
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Xiao‐Peng Gao
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| | - Bin Zang
- Intensive Care Unit Shengjing Hospital, China Medical University Shenyang China
| |
Collapse
|
|
18
|
Du D, Yao L, Zhang R, Shi N, Shen Y, Yang X, Zhang X, Jin T, Liu T, Hu L, Xing Z, Criddle DN, Xia Q, Huang W, Sutton R. Protective effects of flavonoids from Coreopsis tinctoria Nutt. on experimental acute pancreatitis via Nrf-2/ARE-mediated antioxidant pathways. JOURNAL OF ETHNOPHARMACOLOGY 2018; 224:261-272. [PMID: 29870787 DOI: 10.1016/j.jep.2018.06.003] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 05/12/2018] [Accepted: 06/01/2018] [Indexed: 02/06/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Oxidative stress is a prominent feature of clinical acute pancreatitis (AP). Coreopsis tinctoria has been used traditionally to treat pancreas disorders like diabetes mellitus in China and Portugal and its flavonoid-rich fraction contain the main phytochemicals that have antioxidant and anti-inflammatory activities. AIM OF THE STUDY To investigate the effects of flavonoids isolated from C. tinctoria on experimental AP and explore the potential mechanism. MATERIALS AND METHODS LC-MS based online technique was used to analyse and isolate targeted flavonoids from C. tinctoria. Freshly isolated mouse pancreatic acinar cells were treated with taurocholic acid sodium salt hydrate (NaT, 5 mM) with or without flavonoids. Fluorescence microscopy and a plate reader were used to determine necrotic cell death pathway activation (propidium iodide), reactive oxygen species (ROS) production (H2-DCFDA) and ATP depletion (luminescence) where appropriate. AP was induced by 7 repeated intraperitoneal caerulein injections (50 μg/kg) at hourly interval in mice or retrograde infusion of taurolithocholic acid 3-sulfate disodium salt (TLCS; 5 mM, 50 μL) into the pancreatic duct in mice or infusion of NaT (3.5%, 1 mL/kg) in rats. A flavonoid was intraperitoneally administered at 0, 4, and 8 h after the first caerulein injection or post-operation. Disease severity, oxidative stress and antioxidant markers were determined. RESULTS Total flavonoids extract and flavonoids 1-6 (C1-C6) exhibited different capacities in reducing necrotic cell death pathway activation with 0.5 mM C1, (2 R,3 R)-taxifolin 7-O-β-D-glucopyranoside, having the best effect. C1 also significantly reduced NaT-induced ROS production and ATP depletion. C1 at 12.5 mg/kg and 8.7 mg/kg (equivalent to 12.5 mg/kg for mice) significantly reduced histopathological, biochemical and immunological parameters in the caerulein-, TLCS- and NaT-induced AP models, respectively. C1 administration increased pancreatic nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-medicated haeme oxygenase-1 expression and elevated pancreatic antioxidant enzymes superoxide dismutase and glutathione peroxidase levels. CONCLUSIONS Flavonoid C1 from C. tinctoria was protective in experimental AP and this effect may at least in part be attributed to its antioxidant effects by activation of Nrf2-mediated pathways. These results suggest the potential utilisation of C. tinctoria to treat AP.
Collapse
Affiliation(s)
- Dan Du
- West China-Washington Mitochondria and Metabolism Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China.
| | - Linbo Yao
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Rui Zhang
- Laboratory of Ethnopharmacology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Na Shi
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Yan Shen
- Laboratory of Ethnopharmacology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Xinmin Yang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Xiaoying Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Tao Jin
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Tingting Liu
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Liqiang Hu
- West China-Washington Mitochondria and Metabolism Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Zhihua Xing
- Laboratory of Ethnopharmacology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - David N Criddle
- Department of Cellular and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3BX, UK
| | - Qing Xia
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China
| | - Wei Huang
- Department of Integrated Traditional Chinese and Western Medicine, Sichuan Provincial Pancreatitis Centre and West China-Liverpool Biomedical Research Centre, West China Hospital/West China Medical School, Sichuan University, Chengdu 610041, China; Liverpool Pancreatitis Study Group, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK.
| | - Robert Sutton
- Liverpool Pancreatitis Study Group, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GE, UK
| |
Collapse
|
|
19
|
Liu X, Zhu Q, Zhang M, Yin T, Xu R, Xiao W, Wu J, Deng B, Gao X, Gong W, Lu G, Ding Y. Isoliquiritigenin Ameliorates Acute Pancreatitis in Mice via Inhibition of Oxidative Stress and Modulation of the Nrf2/HO-1 Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2018; 2018:7161592. [PMID: 29854090 PMCID: PMC5944199 DOI: 10.1155/2018/7161592] [Citation(s) in RCA: 131] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Revised: 02/17/2018] [Accepted: 03/20/2018] [Indexed: 02/06/2023]
Abstract
Oxidative stress plays a crucial role in the pathogenesis of acute pancreatitis (AP). Isoliquiritigenin (ISL) is a flavonoid monomer with confirmed antioxidant activity. However, the specific effects of ISL on AP have not been determined. In this study, we aimed to investigate the protective effect of ISL on AP using two mouse models. In the caerulein-induced mild acute pancreatitis (MAP) model, dynamic changes in oxidative stress injury of the pancreatic tissue were observed after AP onset. We found that ISL administration reduced serum amylase and lipase levels and alleviated the histopathological manifestations of pancreatic tissue in a dose-dependent manner. Meanwhile, ISL decreased the oxidative stress injury and increased the protein expression of the Nrf2/HO-1 pathway. In addition, after administering a Nrf2 inhibitor (ML385) or HO-1 inhibitor (zinc protoporphyrin) to block the Nrf2/HO-1 pathway, we failed to observe the protective effects of ISL on AP in mice. Furthermore, we found that ISL mitigated the severity of pancreatic tissue injury and pancreatitis-associated lung injury in a severe acute pancreatitis model induced by L-arginine. Taken together, our data for the first time confirmed the protective effects of ISL on AP in mice via inhibition of oxidative stress and modulation of the Nrf2/HO-1 pathway.
Collapse
Affiliation(s)
- Xinnong Liu
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Qingtian Zhu
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Min Zhang
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Tao Yin
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Rong Xu
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of General Surgery, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Weiming Xiao
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Jian Wu
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Bin Deng
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Xuefeng Gao
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Weijuan Gong
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Immunology, School of Medicine, Yangzhou University, Yangzhou, China
| | - Guotao Lu
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Yanbing Ding
- Laboratory of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| |
Collapse
|
|
20
|
Diterpene ginkgolides meglumine injection protects against paraquat-induced lung injury and pulmonary fibrosis in rats. Biomed Pharmacother 2018; 99:746-754. [DOI: 10.1016/j.biopha.2018.01.135] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/09/2018] [Accepted: 01/28/2018] [Indexed: 12/29/2022] Open
|
|
21
|
Hawkins KE, DeMars KM, Alexander JC, de Leon LG, Pacheco SC, Graves C, Yang C, McCrea AO, Frankowski JC, Garrett TJ, Febo M, Candelario-Jalil E. Targeting resolution of neuroinflammation after ischemic stroke with a lipoxin A 4 analog: Protective mechanisms and long-term effects on neurological recovery. Brain Behav 2017; 7:e00688. [PMID: 28523230 PMCID: PMC5434193 DOI: 10.1002/brb3.688] [Citation(s) in RCA: 43] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2016] [Revised: 02/21/2017] [Accepted: 02/26/2017] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti-inflammatory, pro-resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML-111. We hypothesized that post-ischemic, intravenous treatment with BML-111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats. Additionally, we investigated the potential protective mechanisms of BML-111 on the post-stroke molecular and cellular profile. METHODS A total of 133 male Sprague-Dawley rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) and BML-111 administration was started at the time of reperfusion. Two methods of week-long BML-111 intravenous administration were tested: continuous infusion via ALZET ® osmotic pumps (1.25 and 3.75 μg μl-1 hr-1), or freshly prepared daily single injections (0.3, 1, and 3 mg/kg). We report for the first time on the stability of BML-111 and characterized an optimal dose and a dosing schedule for the administration of BML-111. RESULTS One week of BML-111 intravenous injections did not reduce infarct size or improve behavioral deficits 4 weeks after ischemic stroke. However, post-ischemic treatment with BML-111 did elicit early protective effects as demonstrated by a significant reduction in infarct volume and improved sensorimotor function at 1 week after stroke. This protection was associated with reduced pro-inflammatory cytokine and chemokine levels, decreased M1 CD40+ macrophages, and increased alternatively activated, anti-inflammatory M2 microglia/macrophage cell populations in the post-ischemic brain. CONCLUSION These data suggest that targeting the endogenous LXA 4 pathway could be a promising therapeutic strategy for the treatment of ischemic stroke. More work is necessary to determine whether a different dosing regimen or more stable LXA 4 analogs could confer long-term protection.
Collapse
Affiliation(s)
- Kimberly E Hawkins
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Kelly M DeMars
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Jon C Alexander
- Department of Anesthesiology University of Florida Gainesville FL USA
| | - Lauren G de Leon
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Sean C Pacheco
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Christina Graves
- Department of Oral Biology University of Florida Gainesville FL USA
| | - Changjun Yang
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Austin O McCrea
- Department of Neuroscience McKnight Brain Institute University of Florida Gainesville FL USA
| | - Jan C Frankowski
- Interdepartmental Neuroscience Program University of California Irvine CA USA
| | - Timothy J Garrett
- Department of Pathology, Immunology and Laboratory Medicine University of Florida Gainesville FL USA
| | - Marcelo Febo
- Department of Psychiatry University of Florida Gainesville FL USA
| | | |
Collapse
|
|
22
|
BML-111 Attenuates Renal Ischemia/Reperfusion Injury Via Peroxisome Proliferator-Activated Receptor-α-Regulated Heme Oxygenase-1. Inflammation 2017; 39:611-24. [PMID: 26597893 DOI: 10.1007/s10753-015-0286-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
We examine whether BML-111, a lipoxin receptor agonist, inhibits renal ischemia/reperfusion (I/R) injury, and whether peroxisome proliferator-activated receptor-α (PPARα) or heme oxygenase-1 (HO-1) is involved in protective effects of BML-111 on kidney against I/R injury. Rats subjected to renal I/R injury were treated with or without BML-111. Renal histological and immunohistochemical studies were performed. Expressions of phosphorylated p38 mitogen-activated protein kinase (pp38 MAPK), phosphorylated PPARα (pPPARα), and HO-1 were assessed in NRK-52E cells exposed to BML-111. The binding activity of PPARα to peroxisome proliferator-responsive element (PPRE) on HO-1 promoter in the cells was determined. BML-111 treatment resulted in a marked reduction in the severity of histological features of renal I/R injury, and attenuated the rise in renal myeloperoxidase and malondialdehyde, blood urea nitrogen and creatinine, urinary N-acetyl-β-glucosaminidase, and leucine aminopeptidase levels caused by I/R injury. BML-111 stimulated the renal expressions of pPPARα and HO-1, and cellular messenger RNA (mRNA) and protein expressions of pPPARα and HO-1 which were both blocked by GW6471, a selective PPARα antagonist, and ZnPP-IX, a specific inhibitor of HO-1 pretreatment. The pp38 MAPK inhibitor SB203580 blocked the BML-111-induced expressions of pp38 MAPK, pPPARα, and HO-1 in NRK-52E cells. The binding activity of PPARα to PPRE in nuclear extracts of NRK-52E cells was enhanced by treatment of the cells with BML-111, and was suppressed by GW6471 and SB203580. BML-111 protects the kidney against I/R injury via activation of p38 MAPK/PPARα/HO-1 pathway.
Collapse
|
|
23
|
El-Tanbouly GS, El-Awady MS, Megahed NA, El-Kashef HA, Salem HA. The lipoxin A 4 agonist BML-111 attenuates acute hepatic dysfunction induced by cecal ligation and puncture in rats. Naunyn Schmiedebergs Arch Pharmacol 2016; 390:361-368. [PMID: 28035464 DOI: 10.1007/s00210-016-1335-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 12/21/2016] [Indexed: 12/11/2022]
Abstract
Sepsis is a systemic inflammatory response associating severe infection leading to multi-organ failure, such as hepatic dysfunction. This study investigates the possible hepatoprotective effect of the lipoxin A4 agonist (BML-111) in cecal ligation and puncture (CLP) model in rats. Pretreatment with BML-111 (1 mg/kg, i.p., 1 h before CLP) protected against CLP-induced mortality after 24 h. BML-111 prevented marked inflammatory cells in liver tissues and decreased elevation in serum hepatic biomarkers [alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TB), gamma-glutamyl transferase (γ-GT)] induced by CLP. Additionally, BML-111 attenuated elevated serum level of interleukin-6 (IL-6) and downregulated hepatic IL-6 mRNA expression. Meanwhile, BML-111 further increased serum IL-10 and upregulated hepatic IL-10 mRNA expression, while it downregulated hepatic mRNA expression of nuclear factor inhibitory protein kappa-B alpha (NFκBia), toll-like receptor-4 (TLR-4), and 5-lipooxygenase (5-LOX). Moreover, BML-111 prevented NF-κB/p65 nuclear translocation and activation. In conclusion, BML-111 attenuated CLP-induced acute hepatic dysfunction through its anti-inflammatory effect by decreasing NF-κB activity, TLR-4, and 5-LOX expression with subsequent decrease in pro-inflammatory IL-6 and elevation in anti-inflammatory IL-10.
Collapse
Affiliation(s)
- Ghada S El-Tanbouly
- Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt
| | - Mohammed S El-Awady
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
| | - Nermeen A Megahed
- Department of Pathology, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Hassan A El-Kashef
- Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.,Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| | - Hatem A Salem
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt
| |
Collapse
|
|
24
|
Chen T, Wang R, Jiang W, Wang H, Xu A, Lu G, Ren Y, Xu Y, Song Y, Yong S, Ji H, Ma Z. Protective Effect of Astragaloside IV Against Paraquat-Induced Lung Injury in Mice by Suppressing Rho Signaling. Inflammation 2016; 39:483-492. [PMID: 26452991 DOI: 10.1007/s10753-015-0272-4] [Citation(s) in RCA: 96] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
The purpose of the present study was to evaluate the protective effects of astragaloside IV (AS IV) against paraquat (PQ)-induced pulmonary injury in vivo. Fifty BALB/C mice were randomized into five groups: (1) control, (2) PQ, (3) PQ + dexamethasone (Dex, 5 mg/kg), (4) PQ + AS IV (50 mg/kg), and (5) PQ + AS IV (100 mg/kg). A single dose of PQ (50 mg/kg, i.p.) was intraperitoneally given to induced acute lung injury. Then, mice were treated with AS IV (50 and 100 mg/kg/day, orally) for 5 days. At the end of the experiment, animals were euthanized; then, the bronchoalveolar lavage fluid (BALF) and lung tissues were collected for histological observation, biochemical assay, and Western blot analysis. Malondialdehyde (MDA), myeloperoxidase (MPO), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in lung tissues, and interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α) levels in BALF were determined. Histological examination indicated that AS IV attenuated lung damage caused by PQ. Biochemical results showed that AS IV treatment significantly reduced the levels of MDA, MPO, and inflammatory cytokines while increased the levels of SOD, CAT, and GSH-Px compared with those in PQ group. Western blot results revealed that AS IV attenuated the Txnip/Trx expressions and inhibited Rho/ROCK/nuclear factor kappaB (NF-κB) signaling pathway in PQ-challenged mice. These findings suggested the protective effect of AS IV as a natural product on PQ-induced pulmonary injury.
Collapse
Affiliation(s)
- Tong Chen
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Ruoning Wang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Wenjiao Jiang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Huimin Wang
- School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
| | - Ang Xu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Guo Lu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Yi Ren
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Yangmei Xu
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Yangyang Song
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China
| | - Shoulei Yong
- School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, China
| | - Hui Ji
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
| | - Zhanqiang Ma
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. .,Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, Nanjing, 210009, China.
| |
Collapse
|
|
25
|
Dong Z, Shang H, Chen YQ, Pan LL, Bhatia M, Sun J. Sulforaphane Protects Pancreatic Acinar Cell Injury by Modulating Nrf2-Mediated Oxidative Stress and NLRP3 Inflammatory Pathway. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2016; 2016:7864150. [PMID: 27847555 PMCID: PMC5101394 DOI: 10.1155/2016/7864150] [Citation(s) in RCA: 61] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/16/2016] [Accepted: 10/03/2016] [Indexed: 12/22/2022]
Abstract
Acute pancreatitis (AP) is characterized by early activation of intra-acinar proteases followed by acinar cell death and inflammation. Cellular oxidative stress is a key mechanism underlying these pathological events. Sulforaphane (SFN) is a natural organosulfur antioxidant with undescribed effects on AP. Here we investigated modulatory effects of SFN on cellular oxidation and inflammation in AP. AP was induced by cerulean hyperstimulation in BALB/c mice. Treatment group received a single dose of 5 mg/kg SFN for 3 consecutive days before AP. We found that SFN administration attenuated pancreatic injury as evidenced by serum amylase, pancreatic edema, and myeloperoxidase, as well as by histological examination. SFN administration reverted AP-associated dysregulation of oxidative stress markers including pancreatic malondialdehyde and redox enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In acinar cells, SFN treatment upregulated nuclear factor erythroid 2-related factor 2 (Nrf2) expression and Nrf2-regulated redox genes including quinoneoxidoreductase-1, heme oxidase-1, SOD1, and GPx1. In addition, SFN selectively suppressed cerulein-induced activation of the nucleotide-binding domain leucine-rich repeat containing family, pyrin domain-containing 3 (NLRP3) inflammasome, in parallel with reduced nuclear factor- (NF-) κB activation and modulated NF-κB-responsive cytokine expression. Together, our data suggested that SFN modulates Nrf2-mediated oxidative stress and NLRP3/NF-κB inflammatory pathways in acinar cells, thereby protecting against AP.
Collapse
Affiliation(s)
- Zhaojun Dong
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Haixiao Shang
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Yong Q. Chen
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Jiangnan University School of Medicine, Wuxi 214122, China
| | - Li-Long Pan
- Shanghai Key Laboratory of Bioactive Small Molecules and Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Madhav Bhatia
- Inflammation Research Group, Department of Pathology, University of Otago, Christchurch, 2 Riccarton Avenue, P.O. Box 4345, Christchurch 8140, New Zealand
| | - Jia Sun
- State Key Laboratory of Food Science and Technology, School of Food Science and Technology, Jiangnan University, Wuxi 214122, China
- Jiangnan University School of Medicine, Wuxi 214122, China
| |
Collapse
|
|
26
|
Cai Y, Shen Y, Xu G, Tao R, Yuan W, Huang Z, Zhang D. TRAM1 protects AR42J cells from caerulein-induced acute pancreatitis through ER stress-apoptosis pathway. In Vitro Cell Dev Biol Anim 2016; 52:530-6. [DOI: 10.1007/s11626-016-0011-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Accepted: 02/17/2016] [Indexed: 12/31/2022]
|
|
27
|
Quantitative Evaluation and Selection of Reference Genes for Quantitative RT-PCR in Mouse Acute Pancreatitis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:8367063. [PMID: 27069927 PMCID: PMC4812220 DOI: 10.1155/2016/8367063] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 01/19/2016] [Accepted: 02/07/2016] [Indexed: 02/05/2023]
Abstract
The analysis of differences in gene expression is dependent on normalization using reference genes. However, the expression of many of these reference genes, as evaluated by quantitative RT-PCR, is upregulated in acute pancreatitis, so they cannot be used as the standard for gene expression in this condition. For this reason, we sought to identify a stable reference gene, or a suitable combination, for expression analysis in acute pancreatitis. The expression stability of 10 reference genes (ACTB, GAPDH, 18sRNA, TUBB, B2M, HPRT1, UBC, YWHAZ, EF-1α, and RPL-13A) was analyzed using geNorm, NormFinder, and BestKeeper software and evaluated according to variations in the raw Ct values. These reference genes were evaluated using a comprehensive method, which ranked the expression stability of these genes as follows (from most stable to least stable): RPL-13A, YWHAZ > HPRT1 > GAPDH > UBC > EF-1α > 18sRNA > B2M > TUBB > ACTB. RPL-13A was the most suitable reference gene, and the combination of RPL-13A and YWHAZ was the most stable group of reference genes in our experiments. The expression levels of ACTB, TUBB, and B2M were found to be significantly upregulated during acute pancreatitis, whereas the expression level of 18sRNA was downregulated. Thus, we recommend the use of RPL-13A or a combination of RPL-13A and YWHAZ for normalization in qRT-PCR analyses of gene expression in mouse models of acute pancreatitis.
Collapse
|
|
28
|
Lv P, Li HY, Ji SS, Li W, Fan LJ. Thalidomide Inhibits Adhesion Molecules in Experimental Acute Pancreatitis-Associated Lung Injury. Drug Dev Res 2015; 76:24-30. [PMID: 25620023 DOI: 10.1002/ddr.21237] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2014] [Accepted: 12/10/2014] [Indexed: 12/30/2022]
Abstract
Preclinical Research The study evaluated the effect of thalidomide on adhesion molecule expression in acute pancreatitis-associated lung injury in rats. Acute pancreatitis was induced in rats by retrograde infusion of 5% sodium taurocholate into the bile-pancreatic duct, and thalidomide (100 mg/kg) was given daily by intragastric route for 8 days before this treatment. Serum lipase (LPS), protein levels in bronchoalveolar lavage fluid (BALF), superoxide dismutase (SOD), glutathione peroxidase (GSHpx), and malondialdehyde (MDA) levels in lung were measured. Compared with the acute pancreatitis- group, lung histopathology, serum LPS, protein levels in BALF, SOD, GSHpx, and MDA levels, and the expression levels of intercellular adhesion molecule-1 and E-selectin mRNA and protein in rats given thalidomide were improved (P < 0.01). Thus, thalidomide may reduce the expression of adhesion molecules via inhibition of oxidative stress to alleviate acute pancreatitis-associated lung injury in a rat model. Drug Dev Res, 2014. © 2014 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Peng Lv
- Department of Gastroenterology, Jining First People's Hospital, Jining, 272111, China
| | | | | | | | | |
Collapse
|