Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Hyperhomocysteinemia exacerbates cisplatin-induced acute kidney injury in mice by upregulating the expression of endoplasmic reticulum stress protein

Mei Zhang¹, Yanjun Long^1,2 , Yan Zha^1,2, Jing Yuan^1,2, Yan Ran^1,2

¹Guizhou University School of Medicine, Guizhou University, Guiyang; ²Division of Nephrology, Guizhou Provincial People's Hospital, Guizhou Provincial Institute of Nephritic & Urinary Disease, East ZhongShan Road 83, Guizhou 550002, PR China.

For correspondence:- Yanjun Long Email: mag2zu@163.com

Accepted: 28 October 2020 Published: 30 November 2020

Citation: Zhang M, Long Y, Zha Y, Yuan J, Ran Y. Hyperhomocysteinemia exacerbates cisplatin-induced acute kidney injury in mice by upregulating the expression of endoplasmic reticulum stress protein. Trop J Pharm Res 2020; 19(11):2337-2342 doi: 10.4314/tjpr.v19i11.13

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the effect of hyperhomocysteinemia on cisplatin-induced acute kidney damage, as well as the mechanism involved.

Methods: Forty-eight healthy mice were assigned to control and model groups, having 16 and 32 mice, respectively. Cisplatin was intraperitoneally given to model mice at a level of 20 mg/kg. Serum levels of homocysteine (Hcy), BUN and creatinine (Scr) were measured in each group, and changes in kidney coefficient were calculated. Changes in levels of glucose regulatory protein 78 (GRP78) and cysteine-dependent aspartate-directed protease-12 (Caspase-12) were determined with immunohistochemistry and Western blot assay.

Results: Serum Hcy, BUN, Scr, renal coefficient, and the expression levels of GRP78 and Caspase-12 in kidney of model mice were markedly elevated, relative to control values (p < 0.05). However, relative to model mice, serum Hcy, BUN, Scr, renal coefficient, apoptosis level of renal tubular epithelial cells, and GRP78, Caspase-12 expression levels in renal tissue were significantly increased in the high-methionine intervention group (p < 0.05).

Conclusion: Cisplatin induces acute renal injury in mice. Hyperhomocysteinemia may aggravate cisplatin-induced acute renal injury by upregulating the expression of endoplasmic reticulum stress protein.

Keywords: Hyperhomocysteinemia, Endoplasmic reticulum stress protein, Cisplatin, Acute kidney injury