Department of Pharmacology and Toxicology, Nizam Institute of Pharmacy, Jawaharlal Nehru Technological University, Hyderabad, Telangana, India.
Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
Hum Exp Toxicol. 2020 Sep;39(9):1257-1267. doi: 10.1177/0960327120918306. Epub 2020 Apr 15.
This study investigated the effect of carvedilol on aspirin-induced gastric damage. Male Wistar rats were divided into three groups. Control rats received the vehicle, while the aspirin group received aspirin (200 mg/kg) orally for 4 days. Rats of aspirin + carvedilol group were administered aspirin along with carvedilol (5 mg/kg; intraperitoneal) for 4 days. Animals were euthanized at the end of the treatment period, and gastric tissues were collected to perform histopathological and mechanistic studies. The results revealed that aspirin administration induced gastric ulcer as there were remarkable histopathological lesions in the form of marked necrosis, inflammation, hemorrhage, edema, and dysplastic changes. Lipid peroxidative markers such as malondialdehyde, 4-hydroxynonenal, and protein carbonyl were significantly elevated in the aspirin group. This was concurrent with a significant amelioration of antioxidants such as reduced glutathione, superoxide dismutase, and catalase. Furthermore, aspirin increased the immunoexpression of cyclooxygenase (COX) 2 and nuclear factor kappa-B (NF-κB). Aspirin induced elevation in the inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Aspirin enhanced the immunoexpression of inducible nitric oxide synthetase (iNOS) and increased the level of nitrite/nitrate in gastric tissue. On the other hand, carvedilol treatment reversed all these pathological changes. Carvedilol succeeded to enhance antioxidants in gastric tissue, attenuated lipid peroxidative parameters, and suppressed the release of inflammatory mediators. It attenuated the immunoexpression of COX-2, NF-κB, and iNOS. Collectively, carvedilol has a gastro-protective effect that could be attributed to its antioxidative and anti-inflammatory properties, which modulate NF-κB/COX-2/iNOS pathways.
这项研究调查了卡维地洛对阿司匹林引起的胃损伤的影响。雄性 Wistar 大鼠被分为三组。对照组大鼠给予载体，而阿司匹林组大鼠连续 4 天口服给予阿司匹林（200mg/kg）。阿司匹林+卡维地洛组大鼠同时给予阿司匹林和卡维地洛（5mg/kg；腹腔内），连续 4 天。在治疗期末处死动物，收集胃组织进行组织病理学和机制研究。结果表明，阿司匹林给药诱导了胃溃疡，因为有明显的组织病理学损伤，表现为明显的坏死、炎症、出血、水肿和发育不良改变。脂质过氧化标志物如丙二醛、4-羟壬烯醛和蛋白质羰基在阿司匹林组显著升高。这与抗氧化剂如还原型谷胱甘肽、超氧化物歧化酶和过氧化氢酶的显著改善相一致。此外，阿司匹林增加了环氧化酶（COX）2 和核因子 kappa-B（NF-κB）的免疫表达。阿司匹林诱导肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β等炎症细胞因子的升高。阿司匹林增强了诱导型一氧化氮合酶（iNOS）的免疫表达，并增加了胃组织中硝酸盐/亚硝酸盐的水平。另一方面，卡维地洛逆转了所有这些病理变化。卡维地洛成功地增强了胃组织中的抗氧化剂，减轻了脂质过氧化参数，并抑制了炎症介质的释放。它减轻了 COX-2、NF-κB 和 iNOS 的免疫表达。总之，卡维地洛具有胃保护作用，这可能归因于其抗氧化和抗炎特性，调节 NF-κB/COX-2/iNOS 途径。
