Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
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
Processing time: 298 Days and 4.6 Hours
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.