title: Chromium-induced nephrotoxicity and ameliorative effect of carvedilol in rats: Involvement of oxidative stress, apoptosis and inflammation.
abstract: 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 β-adrenergic blocker using rat model of potassium dichromate-induced nephrotoxicity. Rats were pretreated with carvedilol (10mg/kg) for 21days. A single subcutaneous injection of potassium dichromate (15mg/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 NF-κB (p65) in kidney tissues. The serum levels of TNF-α 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.
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Bidya Dhar
authors.initials: BD
authors.lastname: Sahu
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Meghana
authors.initials: M
authors.lastname: Koneru
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Shriharsh R
authors.initials: SR
authors.lastname: Bijargi
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India.
authors.forename: Anudeep
authors.initials: A
authors.lastname: Kota
authors.affiliation: Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology (IICT), Hyderabad 500 007, India. Electronic address: sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D002857:Chromium / Q000633:toxicity*; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009393:Nephritis / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D011192:Potassium Dichromate / Q000633:toxicity; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D002227:Carbazoles; D018836:Inflammation Mediators; D011412:Propanolamines; D000077261:Carvedilol; D002857:Chromium; D011192:Potassium Dichromate
keywords: Apoptosis; Carvedilol; Chromium poisoning; Inflammation; Oxidative stress