Metformin Attenuates Cyclosporine A-induced Renal Fibrosis in Rats.

Abstract

BACKGROUND:

The aim of the present study was to investigate the therapeutic potential of metformin in preventing cyclosporine A (CsA)-induced nephrotoxicity.

METHODS:

Three groups of adult male Sprague-Dawley rats were treated with vehicle, CsA, and CsA + metformin for 4 weeks following 1 week on low sodium diet, respectively. At the end of treatment, all animals were euthanized, and the samples of kidney, urine, and blood were collected for functional, morphological, and molecular biological evaluation.

RESULTS:

Metformin effectively prevented CsA-induced renal dysfunction with increased creatinine clearance rate and reduced blood urea nitrogen and serum creatinine, as well as less proteinuria in comparison to the CsA group. Morphologically, metformin ameliorated CsA-induced renal fibrosis and tissue collapse in the areas of arteries, glomeruli, and proximal tubules. We further demonstrated that the antifibrotic effects of metformin in kidneys treated with CsA were associated with decreased phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2).

CONCLUSIONS:

In conclusion, our study revealed new therapeutic potential of metformin to attenuate calcineurin inhibitor-induced renal fibrosis, which was closely related to the suppression of MEK/ERK1/2 pathway.

• Authors: Can-Xiang Lin, Yan Li, Shi Liang, Jun Tao, Li-Sui Zhang, Yang-Fan Su, Yun-Xi Huang, Zong-Kai Zhao, Shan-Ying Liu, Jun-Meng Zheng
• Journal: Transplantation (Transplantation) Vol. 103 Issue 10 Pg. e285-e296 (10 2019) ISSN: 1534-6080 [Electronic] United States
• PMID: 31335763 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunosuppressive Agents
• Cyclosporine
• Metformin
• Creatinine

Topics

• Animals
• Creatinine (blood, urine)
• Cyclosporine (adverse effects)
• Disease Models, Animal
• Fibrosis
• Humans
• Immunosuppressive Agents (adverse effects)
• Kidney (drug effects, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• Metformin (administration & dosage)
• Oxidative Stress (drug effects)
• Phosphorylation (drug effects)
• Rats
• Rats, Sprague-Dawley
• Renal Elimination (drug effects)