This study evaluates the possible protective effects of gallic acid (GaA) and ferulic acid (FeA) against an experimentally induced liver fibrosis by thioacetamide (TAA) in rats. Animals were divided into: Control group, GaA group (20 mg/kg/day, p.o), FeA (20 mg/kg/day, p.o), TAA group (receiving 250 mg/kg twice/week, I.P), TAA + GaA group, TAA + FeA group (received the same previous doses) and TAA+silymarin group (received silymarin at 100 mg/kg/day+TAA as mentioned above). After 6 consecutive weeks, animals were sacrificed and the assessment of liver functions, oxidative stress biomarkers and histopathological examination of the liver tissues were performed. In addition, the effect on TGF-β1/Smad3 signaling and the expression of miR-21, miR-30 and miR-200 were evaluated. The results showed that administration of GaA or FeA with TAA induced a significant reduction in serum ALT, AST and ALP activities and protected the integrity of liver tissues. Furthermore, they increased the activities of the hepatic antioxidant enzymes; superoxide dismutase and catalase while decreased malondialdehyde content to a normal level. The hepatic expression of TGF-β1, phosphorylated and total Smad3 proteins were significantly decreased. In addition, miR-21 expression was downregulated while miR-30 and miR-200 expressions were upregulated by administration of gallic acid or ferulic acid. In conclusion, gallic and ferulic acids exhibit hepatoprotective and antioxidant effects against TAA-induced liver fibrosis in rats. These effects are mediated through inhibition of TGF-β1/Smad3 signaling and differentially regulating the hepatic expression level of miR-21, miR-30 and miR-200.
Keywords: Antioxidant; Liver fibrosis; Micro RNA; Smad3; TGF; qRT-PCR.
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