Background: An overdose of paracetamol is a frequent reason for liver and renal 24
toxicity and possible death and curcumin has hepatoprotective properties against liver 25
damage. The exact mechanism of such protection is not clear. Therefore, this study 26
was conducted to examine the molecular levels of the protective effect of curcumin on 27
paracetamol overdose induced hepatic toxicity in rats. Male Wistar rats were allocated 28
into 4 groups. Control group, administered corn oil; curcumin group, administered 29
curcumin (400 mg/kg BW daily intra-gastric) dissolved in corn oil; paracetamol 30
group, administered corn oil with a single dose of paracetamol (500 mg/kg BW intra- 31
gastric) and protective group, administered curcumin with a single dose of 32
paracetamol. Curcumin was administered for 7 successive days, while paracetamol 33
was administered at day six of treatment. Blood and liver tissues were collected for 34
biochemical, histopathological, immunohistochemical and molecular examination. 35
Results: Serum analysis revealed an alteration in parameters of kidney and liver. A 36
decrease in the antioxidant activity of liver was recorded in paracetamol group while 37
curcumin administration restored it. Histopathological findings showed an extensive 38
coagulative necrosis in hepatocytes together with massive neutrophilic and 39
lymphocytic infiltration. Immunostaining of liver matrix metalloproteinase-8 (MMP- 40
8) in paracetamol administered rats showed an increase in MMP-8 expression in the 41
area of coagulative necrosis surrounding the central vein of hepatic lobules. Curcumin 42
administration decreased MMP-8 expression in liver of paracetamol administered rats. 43
Gene expression measurements revealed that paracetamol decreased the expression of 44
antioxidant genes and increased the expression of interleukin-1b (IL-1b), IL-8, tumor 45
necrosis factor-a (TNF-a) and acute phase proteins. Curcumin administration 46
3
ameliorated paracetamol-induced alterations in genes expression of antioxidant and 47
inflammatory cytokines. 48
Conclusion: The results clarified the strong protective effect of curcumin on 49
paracetamol induced hepatic toxicity in rats at the immunohistochemical and 50
molecular levels. |
