title: Nebivolol Ameliorates Cisplatin-Induced Nephrotoxicity in Rats.
abstract: Treatment with cisplatin is associated with dose-limiting side effects, mainly nephrotoxicity. On the other hand, nebivolol, a β1 -adrenoceptor antagonist, exhibits vasodilatory and antioxidative properties. This study aimed to determine whether nebivolol possesses a protective effect against cisplatin nephrotoxicity and explore many mechanisms underlying this potential effect. Nephrotoxicity was induced in Wistar rats by a single intraperitoneal injection of cisplatin (6 mg/kg) on day 2. Nebivolol (10 mg/kg) was administered orally for 7 consecutive days. Nebivolol showed a nephroprotective effect as demonstrated by the significant reduction in the elevated levels of serum creatinine and urea as well as renal levels of malondialdehyde, nitric oxide products (nitrite/nitrate), inducible nitric oxide synthase, tumour necrosis factor-alpha, caspase-3, angiotensin II and endothelin-1 with a concurrent increase in renal levels of reduced glutathione and endothelial nitric oxide synthase compared to untreated rats. Histopathological examination confirmed the nephroprotective effect of nebivolol. Pre-treatment with Nω -nitro-L-arginine methyl ester, the non-specific nitric oxide synthase inhibitor, partially altered the protection afforded by nebivolol. In conclusion, nebivolol protects rats against cisplatin-induced nephrotoxicity that is most likely through its antioxidant, anti-inflammatory and antiapoptotic effects as well as by abrogation of the augmented angiotensin II and endothelin-1 levels.
authors.affiliation: Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia.|Department of Pharmacology, Faculty of Medicine, Minia University, El-Minia, Egypt.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Morsy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
authors.forename: Gehan H
authors.initials: GH
authors.lastname: Heeba
mesh_terms: D058665:Adrenergic beta-1 Receptor Agonists / Q000494:pharmacology*; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood; D019332:Endothelin-1 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D000068577:Nebivolol / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000097:blood
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D000970:Antineoplastic Agents; D019332:Endothelin-1; D000068577:Nebivolol; D000804:Angiotensin II; D014508:Urea; D003404:Creatinine; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D002945:Cisplatin; D019331:NG-Nitroarginine Methyl Ester