Journal
CHEMICO-BIOLOGICAL INTERACTIONS
Volume 223, Issue -, Pages 69-79Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.cbi.2014.09.009
Keywords
Carvedilol; Chromium poisoning; Oxidative stress; Apoptosis; Inflammation
Funding
- SMiLE project from CSIR, New Delhi, India [CSC 0111]
- Council of Scientific and Industrial Research (CSIR), New Delhi
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Nephrotoxicity is a major adverse effect of chromium poisoning. In the present study, we investigated the potential renoprotective effect and underlying mechanisms of carvedilol, a non-specific beta-adrenergic blocker using rat model of potassium dichromate-induced nephrotoxicity. Rats were pretreated with carvedilol (10 mg/kg) for 21 days. A single subcutaneous injection of potassium dichromate (15 mg/kg, s.c.) resulted in a significant increase in the levels of blood urea nitrogen and serum creatinine, markers related to oxidative stress, nitrosative stress, apoptosis and inflammation accompanied with histopathological changes in kidney tissues. Exploration of the underlying renoprotective mechanisms of carvedilol revealed that carvedilol attenuated nuclear translocation and DNA binding activity of NE-kappa B (p65) in kidney tissues. The serum levels of TNF-alpha and the renal expression of iNOS and tissue nitrites were significantly decreased in carvedilol plus potassium dichromate administered rats. Carvedilol pretreatment significantly attenuated the potassium dichromate-induced DNA damage, decreased the p53, Bax and cleaved caspase-3 expression and increased the Bcl-2 expression. Moreover, pretreatment with carvedilol significantly restored the renal tissue antioxidant and mitochondrial respiratory enzyme activities and decreased the elevated lipid peroxidation biomarkers to normal. These results were further supported and confirmed by histopathological findings. In conclusion, the findings of the present study demonstrated that carvedilol is an effective chemoprotectant against potassium dichromate-induced nephrotoxicity in rats. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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