Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p < 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.

氧化应激被认为是氯贝贝酸盐（CF）肝毒性的主要机制。为了获得具有低血脂，抗氧化剂和改善肝损伤的多功能新型降血脂药，通过分子杂交合成了氯纤维酸衍生物羟基酪醇-氯贝特酸盐（CF-HT）。CF-HT在Triton W R 1339诱导的高脂血症小鼠中表现出明显的低血脂症，使血清甘油三酸酯（TG），总胆固醇（TC）和丙二醛（MDA）降低了30％，33％和29％。CF-HT还显示了保肝作用，观察到肝指数毒性显着降低，即天冬氨酸和乳酸转氨酶（AST和ALT）活性，碱性磷酸酶（ALP）和总胆红素（TBIL）水平。肝重量和肝系数也得到改善。血清超氧化物歧化酶（SOD）显着升高，血清过氧化氢酶（CAT）和丙二醛（MDA）含量显着恢复。与CF处理的小鼠相比，CF-HT可以显着增加肝谷胱甘肽（GSH）的含量，降低肝氧化谷胱甘肽（GSSG）的含量（p <0.05）。此外，通过CF-HT治疗，肝细胞增生和肥大的组织病理学损害也得到了明显改善。因此，结果表明CF-HT具有更强的降血脂活性和明确的肝保护作用，这可能与其在小鼠中的抗氧化特性有关。