Department of Pharmacology and Toxicology, Faculty of Pharmacy and Pharmaceutical Sciences, Tehran Medical Sciences-Islamic Azad University, Tehran, Iran.
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
J Biochem Mol Toxicol. 2024 Aug;38(8):e23788. doi: 10.1002/jbt.23788.
In this study, we evaluated the hepatoprotective effects of astaxanthin, a natural carotenoid, against the cholestatic liver fibrosis induced by bile duct ligation (BDL). Toward this end, male rats were subjected to BDL and treated with astaxanthin for 35 days. Afterwards, their serum and liver biochemical factors were assessed. Also, histopathological and immunohistochemical analyses were performed to determine the fibrosis and the expression levels of alpha-smooth muscle actin (α-SMA) and transforming growth factor beta (TGF-ß1) in the liver tissue. Based on the results, BDL caused a significant increase in liver enzyme levels, blood lipids, and bilirubin, while decreasing the activity of superoxide dismutase(SOD), catalase (CAT), and glutathione (GSH) enzymes. Also, in the BDL rats, hepatocyte necrosis, infiltration of inflammatory lymphocytes, and hyperplasia of bile ducts were detected, along with a significant increase in α-SMA and TGF-ß1 expression. Astaxanthin, however, significantly prevented the BDL's detrimental effects. In all, 10 mg/kg of this drug maintained the bilirubin and cholesterol serum levels of BDL rats at normal levels. It also reduced the liver enzymes' activity and serum lipids, while increasing the SOD, CAT, and GSH activity in BDL rats. The expression of α-SMA and TGF-ß1 in the BDL rats treated with 10 mg/kg of astaxanthin was moderate (in 34%-66% of cells) and no considerable cholestatic fibrosis was observed in this group. However, administrating the 20 mg/kg of astaxanthin was not effective in this regard. These findings showed that astaxanthin could considerably protect the liver from cholestatic damage by improving the biochemical features and regulating the expression of related proteins.
在这项研究中，我们评估了虾青素（一种天然类胡萝卜素）对胆管结扎（BDL）诱导的胆汁淤积性肝纤维化的肝保护作用。为此，雄性大鼠接受 BDL 并接受虾青素治疗 35 天。之后，评估了他们的血清和肝脏生化因素。还进行了组织病理学和免疫组织化学分析，以确定纤维化以及肝脏组织中α-平滑肌肌动蛋白（α-SMA）和转化生长因子β（TGF-ß1）的表达水平。根据结果，BDL 导致肝酶水平、血脂和胆红素显著增加，而超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）酶的活性降低。此外，在 BDL 大鼠中，检测到肝细胞坏死、炎症淋巴细胞浸润和胆管增生，同时α-SMA 和 TGF-ß1 的表达显著增加。然而，虾青素显著阻止了 BDL 的有害作用。总的来说，10mg/kg 的这种药物将 BDL 大鼠的胆红素和胆固醇血清水平维持在正常水平。它还降低了肝酶的活性和血清脂质，同时增加了 BDL 大鼠中 SOD、CAT 和 GSH 的活性。在接受 10mg/kg 虾青素治疗的 BDL 大鼠中，α-SMA 和 TGF-ß1 的表达适度（在 34％-66％的细胞中），并且在该组中未观察到明显的胆汁淤积性纤维化。然而，给予 20mg/kg 的虾青素在这方面没有效果。这些发现表明，虾青素可以通过改善生化特征和调节相关蛋白的表达，显著保护肝脏免受胆汁淤积性损伤。
