Transforming Growth Factor-β1/Smad3 Signaling and Redox Status in Experimentally Induced Nephrotoxicity: Impact of Carnosine

Abstract

Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups. CCl4 (3 ml/kg body weight; biweekly for 4 weeks) was given to group II and III. Carnosine (10 mg/kg body weight; once daily for 4 weeks) was given to group III and VI. Transforming growth factor-β1 (TGF-β1) level by immunoassay and Smad3 mRNA level by real-time PCR were estimated in addition to cytochrome P450 2E1 (CYP2E1) activity, renal functions, redox status assessment and histopathological examination of the kidney. Carnosine significantly improved kidney function, renal redox status, decreased renal CYP2E1 activity, TGF-β1 level and Smad3 gene expression when compared to CCL4-intoxicated group. The protective effect of carnosine was confirmed by histopathological study. In conclusion: carnosine has the ability to protect against CCl4-induced nephrotoxicity possibly by alleviating oxidative stress, normalizing kidney histopathological architecture in addition to the disruption of the inflammatory and fibrotic response induced by CCl4.