Alpha-lipoic acid as a therapeutic agent in ibuprofen-induced liver fibrosis in a rat model

Abstract

Aim: Ibuprofen (IBU), a commonly used nonsteroidal antiinflammatory drug, may cause hepatotoxicity and fibrosis with prolonged or high-dose use. Alpha-lipoic acid a natural antioxidant, has shown protective effects against oxidative stress and liver injury. The potential therapeutic role of ALA in IBU-induced liver fibrosis was evaluated.

Materials and Methods: Thirty male Wistar Albino rats were divided into five groups (n = 6): control, sham (corn oil), IBU (200 mg/kg by oral gavage for 21 days), IBU + ALA (IBU for 21 days followed by ALA 100 mg/kg by oral gavage for 7 days), and ALA (100 mg/kg for 7 days). Liver tissue was analyzed histopathologically with hematoxylin-eosin and Masson’s trichrome staining and immunohistochemically for TLR4, TGF-β, and α-SMA expression. Data were analyzed using GraphPad Prism 10, with normality assessed by Shapiro-Wilk, group comparisons by analysis of variance or Kruskal-Wallis, and p < 0.05 considered significant.

Results: IBU caused significant hydropic degeneration, sinusoidal dilatation, and perivascular collagen accumulation compared with controls (p<0.001). ALA treatment significantly reduced sinusoidal dilatation (p<0.01) and perivascular fibrosis (p<0.001) significantly but had no significant effect on hydropic degeneration. Immunohistochemistry showed increased TLR4, TGF-β, and α-SMA expression in the IBU group (p<0.001). ALA significantly decreased TLR4 (p<0.001) and α-SMA (p<0.001), while reduction in TGF-β was not statistically significant.

Conclusion: Although ALA alleviates IBU-induced liver fibrosis by suppressing inflammatory signaling (TLR4) and hepatic stellate cell activation (α-SMA), its effect on TGF-β-mediated fibrogenesis is limited. These findings suggest that ALA may help prevent nonsteroidal anti-inflammatory drug-induced liver injury, but further studies with longer treatment durations are needed.