Effect of Piperine Pretreatment on Biochemical Profiles of Acetaminophen-Induced Hepatotoxicity in Rats

Abstract

BACKGROUND AND OBJECTIVE: Acetaminophen overdose is the most frequent cause of liver injuries. N-acetyl-p-benzoquinone imine (NAPQI) has been proposed as the toxic metabolite of acetaminophen induced by cytochrome P-450. Piperine has antioxidant activities and has been introduced as an inhibitor of CYP3A and P4502E1 activities. This study was done to evaluate pretreatment effect of piperine in acetaminophen induced hepatotoxicity in rat.METHODS: In this study, the rats (weighing 150-250g) were divided into 5 groups: saline, piperine (10 mg/kg), acetaminophen (sequential doses of 500 and 1000 mg/kg within 18 hours), piperine with acetaminophen and silymarin (25 mg/kg) with acetaminophen. Activity of alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase in serum were evaluated and the total antioxidant activity was measured by FRAP method.FINDINGS: Piperine as pretreatment prevented increasing in AST and ALT after acute acetaminophen poisoning (respectively, 1711.25±1108.65 and 496±463.55, compared to acetaminophen, 3956.29±5934.73 and 1914.57±3413.47). Total antioxidant level in acetaminophen group was higher than the saline and piperine groups (respectively, p<0.009 and p<0.003) but no statistical significant differences in results were seen between piperine- acetaminophen and silymarin-acetaminophen groups.CONCLUSION: Piperine may partially prevent increasing level of the enzymes after acetaminophen poisoning. It may be concluded that in presence of piperine the level of antioxidants trends to be decreased. In other word, piperine can decrease the need of high antioxidant capacity to deal NAPQI produced following acetaminophen induced hepatotoxicity.

Keywords

• acetaminophen
• piperine
• silymarin
• n-acetyl-p-benzoquinone imine
• aspartate aminotransferase
• alanine aminotransferase
• antioxidant
• ferric reducing ability of plasma