Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice.

Fengfeng LI; Man Jiang; Minghui MA; Xuyang Chen; Yidan Zhang; Yixin Zhang; Yuanyuan YU; Yunfeng Cui; Jiahui Chen; Hui Zhao; Zhijie Sun; Deli Dong

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Anthelmintics nitazoxanide protects against experimental hyperlipidemia and hepatic steatosis in hamsters and mice.

Author: Fengfeng LI ¹ ; Man JIANG ¹ ; Minghui MA ¹ ; Xuyang CHEN ¹ ; Yidan ZHANG ¹ ; Yixin ZHANG ¹ ; Yuanyuan YU ¹ ; Yunfeng CUI ¹ ; Jiahui CHEN ¹ ; Hui ZHAO ¹ ; Zhijie SUN ² ; Deli DONG ¹
Author Information

1. Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), College of Pharmacy, Harbin Medical University, Harbin 150086, China.
2. Department of Pharmacology, China Pharmaceutical University, Nanjing 211198, China.
Publication Type:Journal Article
Keywords: AMPK; Autophagy; Hepatic steatosis; Hyperlipidemia; Mitochondrial uncoupling; Nitazoxanide; SQSTM1/P62; Tizoxanide
From: Acta Pharmaceutica Sinica B 2022;12(3):1322-1338
CountryChina
Language:English
Abstract: Lipid metabolism disorders contribute to hyperlipidemia and hepatic steatosis. It is ideal to develop drugs simultaneous improving both hyperlipidemia and hepatic steatosis. Nitazoxanide is an FDA-approved oral antiprotozoal drug with excellent pharmacokinetic and safety profile. We found that nitazoxanide and its metabolite tizoxanide induced mild mitochondrial uncoupling and subsequently activated AMPK in HepG2 cells. Gavage administration of nitazoxanide inhibited high-fat diet (HFD)-induced increases of liver weight, blood and liver lipids, and ameliorated HFD-induced renal lipid accumulation in hamsters. Nitazoxanide significantly improved HFD-induced histopathologic changes of hamster livers. In the hamsters with pre-existing hyperlipidemia and hepatic steatosis, nitazoxanide also showed therapeutic effect. Gavage administration of nitazoxanide improved HFD-induced hepatic steatosis in C57BL/6J mice and western diet (WD)-induced hepatic steatosis in Apoe ^-/- mice. The present study suggests that repurposing nitazoxanide as a drug for hyperlipidemia and hepatic steatosis treatment is promising.