Alanazi Abeer M, Fadda Laila, Alhusaini Ahlam, Ahmad Rehab, Hasan Iman H, Mahmoud Ayman M
Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia.
Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt.
Antioxidants (Basel). 2020 Feb 16;9(2):159. doi: 10.3390/antiox9020159.
Doxorubicin (DOX) is a cytotoxic anthracycline antibiotic and one of the important chemotherapeutic agents for different types of cancers. DOX treatment is associated with adverse effects, particularly cardiac dysfunction. This study examined the cardioprotective effects of carvedilol (CAR) and/or resveratrol (RES) and liposomal RES (LIPO-RES) against DOX-induced cardiomyopathy, pointing to their modulatory effect on oxidative stress, inflammation, S100A1 and sarco/endoplasmic reticulum calcium ATPase2a (SERCA2a). Rats received CAR (30 mg/kg) and/or RES (20 mg/kg) or LIPO-RES (20 mg/kg) for 6 weeks and were challenged with DOX (2 mg/kg) twice per week from week 2 to week 6. DOX-administered rats exhibited a significant increase in serum creatine kinase-MB (CK-MB), troponin-I and lactate dehydrogenase (LDH) along with histological alterations, reflecting cardiac cell injury. Cardiac toll-like receptor 4 (TLR-4), inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α and interleukin (IL)-6 protein expression were up-regulated, and lipid peroxidation was increased in DOX-administered rats. Treatment with CAR, RES or LIPO-RES as well as their alternative combinations ameliorated all observed biochemical and histological alterations with the most potent effect exerted by CAR/LIPO-RES. All treatments increased cardiac antioxidants, and the expression of S100A1 and SERCA2a. In conclusion, the present study conferred new evidence on the protective effects of CAR and its combination with either RES or LIPO-RES on DOX-induced inflammation, oxidative stress and calcium dysregulation.
多柔比星（DOX）是一种具有细胞毒性的蒽环类抗生素，也是用于治疗各类癌症的重要化疗药物之一。DOX治疗会产生副作用，尤其是心脏功能障碍。本研究检测了卡维地洛（CAR）和/或白藜芦醇（RES）以及脂质体白藜芦醇（LIPO - RES）对DOX诱导的心肌病的心脏保护作用，指出它们对氧化应激、炎症、S100A1和肌浆网/内质网钙ATP酶2a（SERCA2a）具有调节作用。大鼠连续6周接受CAR（30毫克/千克）和/或RES（20毫克/千克）或LIPO - RES（20毫克/千克），并从第2周开始至第6周每周两次接受DOX（2毫克/千克）攻击。接受DOX的大鼠血清肌酸激酶同工酶（CK - MB）、肌钙蛋白I和乳酸脱氢酶（LDH）显著升高，同时伴有组织学改变，反映出心脏细胞损伤。接受DOX的大鼠心脏Toll样受体4（TLR - 4）、诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6蛋白表达上调，脂质过氧化增加。用CAR、RES或LIPO - RES及其联合用药治疗改善了所有观察到的生化和组织学改变，其中CAR/LIPO - RES的效果最为显著。所有治疗均增加了心脏抗氧化剂以及S100A1和SERCA2a的表达。总之，本研究为CAR及其与RES或LIPO - RES联合用药对DOX诱导的炎症、氧化应激和钙失调的保护作用提供了新的证据。
