1. The antiprotozoal drug nitazoxanide improves experimental liver fibrosis in mice.
- Author
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Liu KX, Wang ZY, Ying YT, Wei RM, Dong DL, and Sun ZJ
- Subjects
- Animals, Mice, Male, Humans, Cell Line, Hepatic Stellate Cells drug effects, Hepatic Stellate Cells metabolism, Liver Cirrhosis drug therapy, Liver Cirrhosis metabolism, Liver Cirrhosis pathology, Liver Cirrhosis chemically induced, STAT3 Transcription Factor metabolism, STAT3 Transcription Factor antagonists & inhibitors, Smad3 Protein metabolism, Liver Cirrhosis, Experimental chemically induced, Liver Cirrhosis, Experimental pathology, Liver Cirrhosis, Experimental drug therapy, Liver Cirrhosis, Experimental metabolism, Liver Cirrhosis, Experimental prevention & control, Mice, Inbred C57BL, Smad2 Protein metabolism, Nitro Compounds, Thiazoles pharmacology, Thiazoles therapeutic use, Antiprotozoal Agents pharmacology, Antiprotozoal Agents therapeutic use
- Abstract
Nitazoxanide is an FDA-approved antiprotozoal drug. Our previous studies find that nitazoxanide and its metabolite tizoxanide affect AMPK, STAT3, and Smad2/3 signals which are involved in the pathogenesis of liver fibrosis, therefore, in the present study, we examined the effect of nitazoxanide on experimental liver fibrosis and elucidated the potential mechanisms. The in vivo experiment results showed that oral nitazoxanide (75, 100 mg·kg
-1 ) significantly improved CCl4 - and bile duct ligation-induced liver fibrosis in mice. Oral nitazoxanide activated the inhibited AMPK and inhibited the activated STAT3 in liver tissues from liver fibrosis mice. The in vitro experiment results showed that nitazoxanide and its metabolite tizoxanide activated AMPK and inhibited STAT3 signals in LX-2 cells (human hepatic stellate cells). Nitazoxanide and tizoxanide inhibited cell proliferation and collagen I expression and secretion of LX-2 cells. Nitazoxanide and tizoxanide inhibited transforming growth factor-β1 (TGF-β1)- and IL-6-induced increases of cell proliferation, collagen I expression and secretion, inhibited TGF-β1- and IL-6-induced STAT3 and Smad2/3 activation in LX-2 cells. In mouse primary hepatic stellate cells, nitazoxanide and tizoxanide also activated AMPK, inhibited STAT3 and Smad2/3 activation, inhibited cell proliferation, collagen I expression and secretion. In conclusion, nitazoxanide inhibits liver fibrosis and the underlying mechanisms involve AMPK activation, and STAT3 and Smad2/3 inhibition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)- Published
- 2024
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