The effects of carvedilol, metoprolol and propranolol on cisplatin-induced kidney injury

Esmaeeli, A and Keshavarz, Z and Dehdar, F and Assadi, M and Seyedabadi, M (2020) The effects of carvedilol, metoprolol and propranolol on cisplatin-induced kidney injury. Drug and Chemical Toxicology. ISSN 01480545 (In Press)

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The β-adrenoceptor blockers may have anti-oxidant properties or induce β-arrestin recruitment beyond classical desensitization of receptor/G protein coupling, offering potential therapeutic benefits. Here, we investigated the effects of carvedilol, metoprolol and propranolol in an animal model of cisplatin-induced nephrotoxicity. Rats received the β-blockers (3 or 12 mg/kg/day) with or without cisplatin, and kidney function was investigated using renal scintigraphy, histopathology, and serum variables. Metoprolol and propranolol as well as low-dose carvedilol did not alter kidney function, per se. Meanwhile, high-dose carvedilol reduced renal accumulation of Technetium-99m (99mTc)–labeled dimercaptosuccinic acid (99mTc-DMSA) without significant effect on other variables. Furthermore, low-dose carvedilol prevented cisplatin-induced reduction of tracer uptake, but high-dose of this drug aggravated the situation. In this regard, both low and high -doses of carvedilol significantly inhibited cisplatin effects on kidney histology, BUN and creatinine levels. Also, high-dose propranolol inhibited cisplatin adverse effects on radiotracer uptake, histological manifestations, BUN and creatinine levels, while metoprolol failed to cause a notable effect. Taken together, carvedilol and high-dose propranolol may offer potential benefits in cisplatin nephrotoxicity.

Item Type: Article
Uncontrolled Keywords: biased ligand Carvedilol cisplatin metoprolol and propranolol nephrotoxicity β-adrenoceptor
Subjects: QV pharmacology
WJ Urogenital System
Divisions: Faculty of Medicin > Department of Pharmacology
Depositing User: خدیجه شبانکاره
Date Deposited: 21 Dec 2020 10:04
Last Modified: 21 Dec 2020 10:04

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