title: Immunohistochemical and molecular study on the protective effect of curcumin against hepatic toxicity induced by paracetamol in Wistar rats.
abstract: 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.
  
  
  CONCLUSIONS
  The results clarified the strong protective effect of curcumin on paracetamol induced hepatic toxicity in rats at the immunohistochemical and molecular levels.
authors.affiliation: Medical Laboratory Department, Faculty of Applied Medical Sciences, Taif University, Turabah, Saudi Arabia. mohamedsoliman8896@yahoo.com.
authors.forename: Mohamed Mohamed
authors.initials: MM
authors.lastname: Soliman
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdo Nassan
authors.forename: Tamer Ahmed
authors.initials: TA
authors.lastname: Ismail
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000209:Acute-Phase Proteins / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D006505:Hepatitis / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy; D020556:Neutrophil Infiltration; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000209:Acute-Phase Proteins; D018712:Analgesics, Non-Narcotic; D000975:Antioxidants; D016207:Cytokines; D053583:Interleukin-1beta; D016209:Interleukin-8; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen; D020784:Matrix Metalloproteinase 8; D003474:Curcumin