Background: An overdose of paracetamol is a frequent reason for liver and renal toxicity and possible death and
curcumin has hepatoprotective properties against liver damage. The exact mechanism of such protection is not
clear. Therefore, this study was conducted to examine the molecular levels of the protective effect of curcumin on
paracetamol overdose induced hepatic toxicity in rats.
Methods: Male Wistar rats were allocated into 4 groups. Control group, administered corn oil; curcumin group,
administered curcumin (400 mg/kg BW daily intra-gastric) dissolved in corn oil; paracetamol group, administered
corn oil with a single dose of paracetamol (500 mg/kg BW intra-gastric) and protective group, administered
curcumin with a single dose of paracetamol. Curcumin was administered for 7 successive days, while paracetamol
was administered at day six of treatment. Blood and liver tissues were collected for biochemical, histopathological,
immunohistochemical and molecular examination.
Results: Serum analysis revealed an alteration in parameters of kidney and liver. A decrease in the antioxidant
activity of liver was recorded in paracetamol group while curcumin administration restored it. Histopathological
findings showed an extensive coagulative necrosis in hepatocytes together with massive neutrophilic and
lymphocytic infiltration. Immunostaining of liver matrix metalloproteinase-8 (MMP-8) in paracetamol administered
rats showed an increase in MMP-8 expression in the area of coagulative necrosis surrounding the central vein of
hepatic lobules. Curcumin administration decreased MMP-8 expression in liver of paracetamol administered rats.
Gene expression measurements revealed that paracetamol decreased the expression of antioxidant genes and
increased the expression of interleukin-1β (IL-1β), IL-8, tumor necrosis factor-α (TNF-α) and acute phase proteins.
Curcumin administration ameliorated paracetamol-induced alterations in genes expression of antioxidant and
inflammatory cytokines.
Conclusion: The results clarified the strong protective effect |
