Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa

Reactive oxygen species (ROS) and reactive metabolic intermediates generate d from various chemical carcinogens are known to play an important role in cell damage and in the initiation and progression of carcinogenesis. Many r adical scavengers, interestingly naturally occuring antioxidants have been found to be effective in inhibiting the induction of carcinogenesis by a wi de variety of chemical carcinogens. Studies have also indicated that variou s spice principles form an important group as antioxidants. In the present study our goal was to investigate whether piperine an pungent principle of black and long peppers was able to inhibit or reduce the oxidative changes induced by chemical carcinogens in rat intestinal model. Carcinogenesis was initiated in intestinal lumen of male rats with 7,12, dimethyl benzanthrac ene, dimethyl amino-methyl azobenzene and 3-methyl cholenthrene. Oxidative alterations were assessed by determining thiobarbituric reactive substances , mainly malonaldehyde las st measure of lipid peroxidation), thiol status and expression of gamma-GT and Na+-K+-ATPase activity in intestinal mucosa. Data indicated that carcinogens treatment induced GSH depletion with substa ntial increase in thiobarbituric reactive substances and enzyme activities. Piperine treatment with carcinogens resulted in inhibition of thiobarbitur ic reactive substances. It mediated a significant increase in the GSH level s and restoration in gamma-GT and Na+-K+-ATPase activity. The studies thus indicate a protective role of piperine against the oxidative alterations by carcinogens. It may be suggested that piperine modulates the oxidative cha nges by inhibiting lipid peroxidation and mediating enhanced synthesis or t ransport of GSH thereby replenishing thiol redox.