Carotenoids Enrich Fractions Ameliorate Liver Fibrosis Induced by Thioacetamide in Rats: Modulation of Metalloproteinase and Its Inhibitor.

Hepatic fibrosis is a consequence of chronic liver diseases. Metalloproteinase and its inhibitor have crucial roles in the resolution of liver fibrosis. The current relevant study is aimed to evaluate the therapeutic effect of ( extract, astaxanthin-rich fraction, astaxanthin ester-rich fraction, and -carotene-rich fraction as well as their mechanisms of action in curing hepatic fibrosis induced by thioacetamide (TAA). Liver fibrosis was induced using TAA (intraperitoneal injection, two times a week for 6 weeks), in a rat model and extract (200 mg/kg), and other fractions (30 mg/kg) were orally administered daily for 4 weeks after the last TAA injection. Based on HPLC analysis, extract contains -carotene (12.95 mg/g, extract) and free astaxanthin (10.85 mg/g, extract), while HPLC/ESI-MS analysis revealed that extract contains 28 carotenoid compounds including three isomers of free astaxanthin, or -carotene, lutein, 14 astaxanthin mono-esters, 5 astaxanthin di-esters, and other carotenoids. and its fractions reduced liver enzymes, nitric oxide, collagen 1, alpha-smooth muscle actin, and transforming growth factor-beta as well as elevated catalase antioxidant activity compared to the TAA group. Also, extract and its fractions exceedingly controlled the balance between metalloproteinase and its inhibitor, activated Kupffer cells proliferation, and suppressed liver apoptosis, necrobiosis, and fibrosis. These findings conclude that extract and its fractions have an antifibrotic effect against TAA-induced liver fibrosis by regulating the oxidative stress and proinflammatory mediators, suppressing multiple profibrogenic factors, and modulating the metalloproteinase and its inhibitor pathway, recommending extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.