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

Abstract

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.

Keywords:

• Carvedilol
• metoprolol and propranolol
• β-adrenoceptor
• cisplatin
• nephrotoxicity
• biased ligand

Acknowledgments

The researchers received appropriate training for animal care and radioprotection. We thank Tehrandaru pharmaceutical company for providing carvedilol, metoprolol and propranolol APIs, and Dr. Kiarash Tanha for his fruitful comments on statistical methods. The authors declare no conflict of interest with respect to the publication of this manuscript in the current form.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The study was supported by the deputy of research of Bushehr University of Medical Sciences. The study complies with ARRIVE guidelines, and was approved by the ethics committee of Bushehr University of Medical Sciences [IRS.BPUMS.REC.1396.134].