Esmaeeli Abdolhamid, Keshavarz Zahra, Dehdar Firoozeh, Assadi Majid, Seyedabadi Mohammad
Department of Pathology, School of Medicine, Bushehr University of Medical Sciences, Bushehr, Iran.
Department of Molecular Imaging and Radionuclide Therapy (MIRT), Bushehr Medical University Hospital, The Persian Gulf Nuclear Medicine Research Center, Bushehr University of Medical Sciences, Bushehr, Iran.
Drug Chem Toxicol. 2022 Jul;45(4):1558-1564. doi: 10.1080/01480545.2020.1846551. Epub 2020 Nov 16.
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.
β-肾上腺素受体阻滞剂可能具有抗氧化特性，或在受体/G蛋白偶联的经典脱敏作用之外诱导β-抑制蛋白募集，从而带来潜在的治疗益处。在此，我们研究了卡维地洛、美托洛尔和普萘洛尔在顺铂诱导的肾毒性动物模型中的作用。大鼠接受β-阻滞剂（3或12毫克/千克/天），同时给予或不给予顺铂，并使用肾闪烁显像、组织病理学和血清变量来研究肾功能。美托洛尔、普萘洛尔以及低剂量的卡维地洛本身并未改变肾功能。同时，高剂量卡维地洛减少了99m锝（99mTc）标记的二巯基丁二酸（99mTc-DMSA）在肾脏的蓄积，但对其他变量无显著影响。此外，低剂量卡维地洛可预防顺铂诱导的示踪剂摄取减少，但高剂量则使情况恶化。在这方面，低剂量和高剂量的卡维地洛均显著抑制了顺铂对肾脏组织学、血尿素氮和肌酐水平的影响。此外，高剂量普萘洛尔抑制了顺铂对放射性示踪剂摄取、组织学表现、血尿素氮和肌酐水平的不良反应，而美托洛尔未能产生显著影响。综上所述，卡维地洛和高剂量普萘洛尔可能对顺铂肾毒性具有潜在益处。
