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.

摘要

β-肾上腺素受体阻滞剂可能具有抗氧化特性或诱导 β-抑制蛋白募集，超出受体/G 蛋白偶联的经典脱敏作用，提供潜在的治疗益处。在这里，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 受体阻滞剂（3 或 12 mg/kg/天）联合或不联合顺铂，并使用肾闪烁显像、组织病理学和血清变量研究肾功能。美托洛尔和普萘洛尔以及低剂量卡维地洛本身并没有改变肾功能。同时，大剂量卡维地洛减少了锝 99m (99mTc) 标记的二巯基琥珀酸 (99mTc-DMSA) 的肾脏蓄积，而对其他变量没有显着影响。此外，低剂量卡维地洛阻止了顺铂诱导的示踪剂摄取减少，但这种药物的高剂量加重了这种情况。在这方面，低剂量和高剂量的卡维地洛均显着抑制顺铂对肾脏组织学、BUN 和肌酐水平的影响。此外，大剂量普萘洛尔可抑制顺铂对放射性示踪剂摄取、组织学表现、BUN 和肌酐水平的不利影响，而美托洛尔未能引起显着影响。总之，卡维地洛和大剂量普萘洛尔可能对顺铂肾毒性有潜在益处。大剂量普萘洛尔抑制顺铂对放射性示踪剂摄取、组织学表现、BUN 和肌酐水平的不良影响，而美托洛尔未能引起显着影响。总之，卡维地洛和大剂量普萘洛尔可能对顺铂肾毒性有潜在益处。大剂量普萘洛尔抑制顺铂对放射性示踪剂摄取、组织学表现、BUN 和肌酐水平的不良影响，而美托洛尔未能引起显着影响。总之，卡维地洛和大剂量普萘洛尔可能对顺铂肾毒性有潜在益处。