Ali Shimaa O, Darwish Hebatallah A, Ismail Nabila A
Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Basic Clin Pharmacol Toxicol. 2016 May;118(5):369-80. doi: 10.1111/bcpt.12502. Epub 2015 Nov 13.
Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome(®) and α-R-lipoic acid against thioacetamide (TAA)-induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2-4 were allowed to receive daily oral doses of curcumin, silybin phytosome(®) or α-R-lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa-B expression as well as tumour necrosis factor-α and interleukin-6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti-inflammatory activities of curcumin, silybin phytosome(®) and α-R-lipoic acid may confer therapeutic efficacy against chronic hepatitis.
慢性肝炎被公认为是一个全球性的健康问题,它会逐渐发展为肝硬化和肝细胞癌。尽管有大量使用动物模型研究过敏性肝炎的实验,但仍然难以构建出慢性肝炎的模型。因此,本研究旨在引入一种近似人类肝炎慢性化机制的动物模型。该研究还旨在考察姜黄素、水飞蓟宾磷脂复合物(®)和α-R-硫辛酸对硫代乙酰胺(TAA)诱导的大鼠慢性肝炎的肝保护作用。每周三次腹腔注射TAA,剂量为200 mg/kg,持续4周。在此期间结束时,处死一组大鼠,与各自的对照组相比,评估慢性肝炎的发展情况。然后停止给予TAA,将剩余的动物分为四组。第1组不进行处理,而第2 - 4组分别每日口服姜黄素、水飞蓟宾磷脂复合物(®)或α-R-硫辛酸,持续7周。接受补充剂的组中,与TAA给药相关的肝丙二醛水平升高受到抑制。此外,补充剂给药后,谷胱甘肽耗竭、胶原蛋白沉积、巨噬细胞活化和核因子κB表达以及肿瘤坏死因子-α和白细胞介素-6水平均显著降低。肝功能的血清学分析和肝脏组织病理学检查证实了这些结果。上述证据共同表明,姜黄素、水飞蓟宾磷脂复合物(®)和α-R-硫辛酸的抗氧化和抗炎活性可能赋予对慢性肝炎的治疗效果。