Carvedilol: a beta blocker with antioxidant property protects against gentamicin-induced nephrotoxicity in rats.
Gentamicin is an antibiotic effective against gram negative infections, whose clinical use is limited by its nephrotoxicity. Since the pathogenesis of gentamicin-induced nephrotoxicity involves oxygen free radicals, the antioxidant carvedilol may protect against gentamicin-induced renal toxicity. We therefore tested this hypothesis using a rat model of gentamicin nephrotoxicity. Carvedilol (2 mg/kg) was administered intraperitoneally 3 days before and 8 days concurrently with gentamicin (80 mg/kg BW). Estimations of urine creatinine, glucose, blood urea, serum creatinine, plasma and kidney tissue malondialdehyde (MDA) were carried out, after the last dose of gentamicin. Kidneys were also examined for morphological changes. Gentamicin caused marked nephrotoxicity as evidenced by increase in blood urea, serum creatinine and decreased in creatinine clearance. Blood urea and serum creatinine was increased by 883% and 480% respectively with gentamicin compared to control. Carvedilol protected the rats from gentamicin induced nephrotoxicity. Rise in blood urea, serum creatinine and decrease in creatinine clearance was significantly prevented by carvedilol. There was 190% and 377% rise in plasma and kidney tissue MDA with gentamicin. Carvedilol prevented the gentamicin induced rise in both plasma and kidney tissue MDA. Kidney from gentamicin treated rats, histologically showed necrosis and desquamation of tubular epithelial cells in renal cortex, whereas it was very much comparable to control with carvedilol. In conclusion, carvedilol with its antioxidant property protected the rats from gentamicin-induced nephrotoxicity.
Kumar
K V
KV
Department of Clinical Pharmacology & Therapeutics, Nizam's Institute of Medical Sciences, Hyderabad, India.
Shifow
A A
AA
Naidu
M U
MU
Ratnakar
K S
KS
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014508:Urea / Q000097:blood
D000319:Adrenergic beta-Antagonists; D000975:Antioxidants; D002227:Carbazoles; D005839:Gentamicins; D011412:Propanolamines; D017392:Thiobarbituric Acid Reactive Substances; D000077261:Carvedilol; D008315:Malondialdehyde; D014508:Urea