Sinapic acid mitigates gentamicin-induced nephrotoxicity and associated oxidative/nitrosative stress, apoptosis, and inflammation in rats.

AIMS

In this study, the renoprotective functions of sinapic acid (SA), a polyphenol, on gentamicin-induced nephrotoxicity and the pathway that mediates this function were examined.

MAIN METHODS

Kidney function markers (serum urea, uric acid, creatinine, LDH, and γ-GGT) and histopathological examinations of the kidney were used to evaluate gentamicin-induced nephrotoxicity. Oxidative stress markers (lipid peroxidation and total protein), renal nitrosative stress (nitric oxide), antioxidant enzymes (catalase and NP-SH), inflammation markers (NF-κB [p65], TNF-α, IL-6, and myeloperoxidase [MPO]), and apoptotic markers (caspase 3, Bax, and Bcl-2) were also assessed.

KEY FINDINGS

SA (10 and 20mg/kg) pretreatment along with gentamicin restored kidney function, upregulated antioxidant levels, and downregulated lipid peroxidation and nitric oxide levels, resulting in significant decreases in oxidative and nitrosative stress. Gentamicin promoted the upregulation of renal cytokines (TNF-α and IL-6), nuclear NF-κB (p65) expression, NF-κB-DNA binding activity, and MPO activity were significantly down regulated upon SA pretreatment. Furthermore, SA pretreatment downregulated caspase 3 and Bax protein expressions and upregulated Bcl-2 protein expression. SA pretreatment also mitigated the magnitude of histological damage and reduced neutrophil infiltration in renal tubules.

SIGNIFICANCE

These outcomes indicated that SA pretreatment mitigates renal impairment and structural injuries via the downregulation of oxidative/nitrosative stress, inflammation, and apoptosis in the kidney.