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- Title
Captopril Inhibits Thioacetamide-Induced Chronic Liver Injury Associated with the Suppression of Inflammation / Hypoxia-Inducible Factor 1-alpha / Profibrogenic Axis-Mediated Hepatotoxicity in Rats.
- Authors
Bin-Jaliah, Ismaeel
- Abstract
Liver transplantation is the only available method to treat liver failure induced by chronic liver injury. We sought to determine whether the angiotensin-converting enzyme inhibitor, captopril, can inhibit the development of chronic liver injury induced by the hepatotoxic agent thioacetamide (TAA) in association with the suppression of inflammation (hsCRP, TNF-a, and IL-6) / hypoxiainducible factor 1-alpha (HIF-1a) / profibrosis (TIMP-1, MMP-9, and a-SMA) axis that mediates liver injury. Therefore, the model group of rats was injected for eight weeks with 200 mg/kg TAA starting at week two. The protective group was pretreated with 150 mg/kg captopril daily for two weeks prior to TAA injections and continued receiving both capropril and TAA agents until being humanely scrificed at week 10. We observed a substantial damage to liver tissue in the model group as demonstrated by a significant (p<0.0001) increase in blood and hepatic tissue levels of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-a (TNF-a), interleukin-6 (L-6), HIF-1a, tissue inhibitor of metalloproteinases-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), alpha-smooth muscle actin (a-SMA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST). All these parameters were significantly (p<0.0244) protected by captopril. Also, a significant (p<0.0001) positive correlation was observed between a-SMA (profibrosis) and the serum and tissue levels of hsCRP, TNF-a, HIF-1a, TIMP-1, MMP-9, and ALT. Thus, these findings suggest that the induction of chronic liver injury by the hepatotoxic compound, TAA is associated with the upregulation of inflammation/HIF-1a/profibrosis, with captopril exhibiting beneficial hepatic pleotropic effects.
- Subjects
ASPARTATE aminotransferase; HYPOXIA-inducible factors; C-reactive protein; LIVER injuries; CAPTOPRIL; ACE inhibitors
- Publication
International Journal of Morphology, 2023, Vol 41, Issue 2, p362
- ISSN
0717-9367
- Publication type
Article
- DOI
10.4067/s0717-95022023000200362