Transforming Growth Factor-β1/Smad3 Signaling and Redox Status in Experimentally Induced Nephrotoxicity: Impact of Carnosine
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Published on: July 3, 2013
Walaa Arafa Keshk1, Mohamed Alaa Katary2
1Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
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.
Insights
Carnosine protects against carbon tetrachloride (CCl4)-induced kidney damage by reducing oxidative stress and inflammation. This study shows carnosine
Area of Science:
- Biochemistry
- Toxicology
- Nephrology
Background:
- Organic compounds like drugs and toxins induce cellular damage via free radicals.
- Carbon tetrachloride (CCl4) is a known nephrotoxic agent causing kidney damage.
- Carnosine, a naturally occurring dipeptide, possesses antioxidant properties.
Purpose of the Study:
- To investigate the protective effects of carnosine against CCl4-induced nephrotoxicity in rats.
- To evaluate carnosine's impact on oxidative stress markers, kidney function, and histopathology.
Main Methods:
- Sixty male albino rats were divided into four groups: control, CCl4-intoxicated, and CCl4 + carnosine treated.
- Rats received CCl4 (3 ml/kg) biweekly for 4 weeks; carnosine (10 mg/kg) was administered daily.
- Evaluated kidney function, renal redox status, cytochrome P450 2E1 (CYP2E1) activity, transforming growth factor-β1 (TGF-β1) levels, Smad3 mRNA expression, and kidney histopathology.
Main Results:
- Carnosine significantly improved kidney function and renal redox status in CCl4-treated rats.
- Carnosine administration led to decreased renal CYP2E1 activity, TGF-β1 levels, and Smad3 gene expression.
- Histopathological examination confirmed the protective effects of carnosine against CCl4-induced kidney damage.
Conclusions:
- Carnosine demonstrates significant nephroprotective effects against CCl4-induced toxicity.
- The protective mechanism involves alleviating oxidative stress and normalizing kidney architecture.
- Carnosine may counteract CCl4-induced inflammatory and fibrotic responses in the kidney.
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