Li HQ, Liu N, Zheng ZY, Teng HL, Pei J. Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 diabetic db/db mice. World J Diabetes 2022; 13(8): 600-612 [PMID: 36159226 DOI: 10.4239/wjd.v13.i8.600]
Corresponding Author of This Article
Jin Pei, PhD, Professor, Department of Biopharmacy, Jilin University School of Pharmaceutical Sciences, No. 1163, Xinmin street, Changchun 130021, Jilin Province, China. peijin@jlu.edu.cn
Research Domain of This Article
Cardiac & Cardiovascular Systems
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Diabetes. Aug 15, 2022; 13(8): 600-612 Published online Aug 15, 2022. doi: 10.4239/wjd.v13.i8.600
Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 diabetic db/db mice
Hong-Qin Li, Nian Liu, Zong-Yu Zheng, Hao-Lin Teng, Jin Pei
Hong-Qin Li, Jin Pei, Department of Biopharmacy, Jilin University School of Pharmaceutical Sciences, Changchun 130021, Jilin Province, China
Hong-Qin Li, Nian Liu, Zong-Yu Zheng, Hao-Lin Teng, Department of Urology, The First Hospital of Jilin University, Changchun 130021, Jilin Province, China
Author contributions: Pei J and Li HQ contributed to conception and design of the study; Li HQ and Liu N performed the experiment; Zheng ZY organized the database; Teng HL performed the statistical analysis; Li HQ and Liu N wrote the draft of the manuscript; and all authors contributed to manuscript revision, read, and approved the submitted version.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Jin Pei, PhD, Professor, Department of Biopharmacy, Jilin University School of Pharmaceutical Sciences, No. 1163, Xinmin street, Changchun 130021, Jilin Province, China. peijin@jlu.edu.cn
Received: October 18, 2021 Peer-review started: October 18, 2021 First decision: December 27, 2021 Revised: January 26, 2022 Accepted: June 27, 2022 Article in press: June 27, 2022 Published online: August 15, 2022
ARTICLE HIGHLIGHTS
Research background
Diabetic nephropathy (DN) is the leading cause of end-stage kidney disease in the United States and most developed countries. New strategies are required to delay the development and the progression of DN.
Research motivation
Previous studies have shown that clopidogrel administration is an effective means of suppressing inflammation in diabetes. Moreover, clopidogrel can ameliorate diabetes-induced renal fibrosis in a streptozotocin-induced murine model of type 1 diabetes.
Research objectives
We aimed to determine whether treatment with clopidogrel has a preventive or therapeutic effect in the kidneys of obese type 2 diabetic db/db mice.
Research methods
Clopidogrel at doses of 5, 10, or 20 mg/kg was administered by gavage for 12 wk. The body mass, blood glucose, and urinary creatinine and albumin concentrations were measured. Immunohistochemistry, enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction were used to evaluate the expression of cytokines. Fibronectin (FN), and collagen I was assessed using immunohistochemistry.
Research results
Clopidogrel treatment reduced urinary albumin/creatinine ratio. Immunohistochemical staining revealed an amelioration of renal fibrosis, significantly less deposition of FN and collagen I. Lower expression of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β and lower levels of urinary TNF-α, monocyte chemoattractant protein-1 and significantly reduced macrophage infiltration of the db/db mice.
Research conclusions
Clopidogrel prevented renal dysfunction in db/db mice, most likely through inhibition of renal macrophage infiltration and the associated inflammation.
Research perspectives
The present findings suggest a promising alternative approach to the treatment of patients with diabetes and the prevention of DN because clopidogrel is in current use and could be co-administered with other antidiabetic drugs.
