Can disulfiram modulate liver injury in CCl4-induced fibrosis in rats?

Abstract

Aim: This study aimed to evaluate the hepatoprotective and antifibrotic effects of DSF in a rat model of CCl₄-induced liver fibrosis.

Background: Liver fibrosis is a chronic and potentially life-threatening condition characterized by fibroblast proliferation and excessive extracellular matrix deposition. Oxidative stress and inflammation are central mechanisms in its pathogenesis. Disulfiram (DSF), known for its antioxidant and potential antifibrotic properties, may attenuate liver injury.

Methods: Thirty-five male Wistar rats were randomly divided into seven groups (n = 5 per group): Control, Oil, DSF 25 mg/kg, DSF 50 mg/kg, CCl₄, CCl₄ + DSF 25 mg/kg, and CCl₄ + DSF 50 mg/kg. After seven weeks of treatment, liver histopathology, serum liver enzymes (ALT, AST, ALP), and malondialdehyde (MDA) levels were assessed.

Results: CCl₄ administration significantly increased serum ALT and AST levels compared with the Control group (p < 0.001). DSF at 25 mg/kg significantly reduced ALT (p = 0.0265), AST (p = 0.0334), and MDA (p < 0.001) compared with the CCl₄ group. Histopathological analysis revealed improved hepatocyte morphology in the low-dose DSF group (p = 0.0358). However, neither DSF dose produced a significant reduction in collagen deposition or vascular congestion, indicating no clear antifibrotic effect at these doses (>0.9999).

Conclusion: Low-dose DSF demonstrated hepatoprotective effects through improvements in biochemical markers and hepatocyte morphology, but failed to significantly attenuate fibrosis. These findings suggest that lower DSF concentrations (< 25 mg/kg) may offer greater antifibrotic potential and should be further investigated in dose-response studies.