Antifibrotic effect of curcumin, N-acetyl cysteine and propolis extract against bisphenol A-induced hepatotoxicity in rats: Prophylaxis versus co-treatment.

AIMS: Bisphenol A (BPA) has been shown to induce liver fibrosis in rodents. Therefore, this study examined the protective effect of a triple combination of curcumin (Cur), N-acetyl cysteine (NAC) and propolis (Prp) extract against BPA-induced hepatic fibrosis. METHODS: 100 Wistar male rats were equally assigned into 10 groups; one group was designated as control. 10 rats were gavaged with BPA (50 mg/kg/day) for 8 wk and left un-treated (BPA group). The remaining 80 rats were divided into 8 groups, distributed in 2 models. Protective model: rats were daily co-treated with BPA and Cur (100 mg/kg, p.o) or NAC (150 mg/kg, p.o) or Prp (200 mg/kg, p.o) or their combination for 8 wk. Preventive model: rats were daily treated with Cur or NAC or Prp or their combination for 4 wk before BPA administration and then in the same manner as protective model. KEY FINDINGS: Current treatment interventions significantly alleviated BPA-induced hepatic damage and fibrosis. They also restored pro-oxidant/antioxidant balance, shifted cytokine balance towards the anti-inflammatory side, decreasing interleukin-1ß/interleukin-10 ratio. Moreover, these compounds seem to exert anti-apoptotic effects by increasing the immunoexpression of B-cell lymphoma 2 in hepatocytes and decreasing hepatic caspase-3 content. Finally, they ameliorated extracellular matrix turn over through down-regulation of matrix metalloproteinase-9 and up-regulation of tissue inhibitor of matrix metalloproteinase-2 genetic expression. SIGNIFICANCE: Current treatments guarded against BPA-induced hepatic fibrosis due to their antioxidant, anti-inflammatory and anti-apoptotic properties, decreasing extracellular matrix turnover. Interestingly, the triple therapy provided hepatoprotection superior to monotherapy. Besides, prophylactic and concurrent treatments seem to be more effective than concurrent treatments.