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

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 cysteinedependent 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 highmethionine 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.