PMID- 36159226
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220928
IS  - 1948-9358 (Print)
IS  - 1948-9358 (Electronic)
IS  - 1948-9358 (Linking)
VI  - 13
IP  - 8
DP  - 2022 Aug 15
TI  - Clopidogrel delays and can reverse diabetic nephropathy pathogenesis in type 2 
      diabetic db/db mice.
PG  - 600-612
LID - 10.4239/wjd.v13.i8.600 [doi]
AB  - BACKGROUND: Diabetic nephropathy (DN) is the principal cause of end-stage renal 
      disease. Previous studies have shown that clopidogrel can prevent the early 
      progression of renal injury. AIM: To elucidate whether clopidogrel is beneficial 
      against DN by using a db/db mouse model. METHODS: db/db mice with a higher 
      urinary albumin/creatinine ratio (ACR) relative to age- and sex-matched wild-type 
      control mice were randomly allocated to clopidogrel and vehicle treatment groups. 
      Clopidogrel was administered at doses of 5, 10, and 20 mg/kg by gavage for 12 wk. 
      Body mass, blood glucose level, and urinary creatinine and albumin concentrations 
      in each group were measured before and after the intervention. Renal fibrosis was 
      evaluated using periodic acid-Schiff and Masson's trichrome staining. The renal 
      protein expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), 
      and F4/80 was assessed using immunohistochemistry. Urinary TNF-alpha, monocyte 
      chemoattractant protein-1 (MCP-1), and IL-6 levels were analyzed using 
      enzyme-linked immunosorbent assay; TNF-alpha and IL-1beta mRNA expression was measured 
      using real-time quantitative polymerase chain reaction. The protein expression of 
      fibronectin (FN) and collagen I was assessed using immunohistochemistry. RESULTS: 
      Clopidogrel treatment did not affect the body mass or blood glucose level of the 
      db/db mice; however, it increased bleeding time and reduced urinary ACR in a 
      dose-dependent manner. Immunohistochemical staining revealed an amelioration of 
      renal fibrosis, significantly lower deposition of FN and collagen I, and 
      significantly lower expression of the proinflammatory cytokines TNF-alpha and IL-1beta 
      and lower levels of urinary TNF-alpha and MCP-1 in the clopidogrel-treated db/db mice 
      (P < 0.05). Furthermore, clopidogrel significantly reduced macrophage 
      infiltration into the glomeruli of the db/db mice. CONCLUSION: Clopidogrel 
      significantly reduced renal collagen deposition and fibrosis and prevented renal 
      dysfunction in db/db mice, most likely through inhibition of renal macrophage 
      infiltration and the associated inflammation.
CI  - (c)The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Li, Hong-Qin
AU  - Li HQ
AD  - Department of Biopharmacy, Jilin University School of Pharmaceutical Sciences, 
      Changchun 130021, Jilin Province, China.
AD  - Department of Urology, The First Hospital of Jilin University, Changchun 130021, 
      Jilin Province, China.
FAU - Liu, Nian
AU  - Liu N
AD  - Department of Urology, The First Hospital of Jilin University, Changchun 130021, 
      Jilin Province, China.
FAU - Zheng, Zong-Yu
AU  - Zheng ZY
AD  - Department of Urology, The First Hospital of Jilin University, Changchun 130021, 
      Jilin Province, China.
FAU - Teng, Hao-Lin
AU  - Teng HL
AD  - Department of Urology, The First Hospital of Jilin University, Changchun 130021, 
      Jilin Province, China.
FAU - Pei, Jin
AU  - Pei J
AD  - Department of Biopharmacy, Jilin University School of Pharmaceutical Sciences, 
      Changchun 130021, Jilin Province, China. peijin@jlu.edu.cn.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Diabetes
JT  - World journal of diabetes
JID - 101547524
PMC - PMC9412856
OTO - NOTNLM
OT  - Clopidogrel
OT  - Diabetes
OT  - Diabetic nephropathy
OT  - Fibronectin
OT  - Inflammation
COIS- Conflict-of-interest statement: All the authors report no relevant conflicts of 
      interest for this article.
EDAT- 2022/09/27 06:00
MHDA- 2022/09/27 06:01
PMCR- 2022/08/15
CRDT- 2022/09/26 17:33
PHST- 2021/10/18 00:00 [received]
PHST- 2022/01/26 00:00 [revised]
PHST- 2022/06/27 00:00 [accepted]
PHST- 2022/09/26 17:33 [entrez]
PHST- 2022/09/27 06:00 [pubmed]
PHST- 2022/09/27 06:01 [medline]
PHST- 2022/08/15 00:00 [pmc-release]
AID - 10.4239/wjd.v13.i8.600 [doi]
PST - ppublish
SO  - World J Diabetes. 2022 Aug 15;13(8):600-612. doi: 10.4239/wjd.v13.i8.600.