Piperine modulation of carcinogen induced oxidative stress in intestinal mucosa.
Reactive oxygen species (ROS) and reactive metabolic intermediates generated from various chemical carcinogens are known to play an important role in cell damage and in the initiation and progression of carcinogenesis. Many radical scavengers, interestingly naturally occuring antioxidants have been found to be effective in inhibiting the induction of carcinogenesis by a wide variety of chemical carcinogens. Studies have also indicated that various 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 benzanthracene, dimethyl amino-methyl azobenzene and 3-methyl cholenthrene. Oxidative alterations were assessed by determining thiobarbituric reactive substances, mainly malonaldehyde (as a 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 substantial increase in thiobarbituric reactive substances and enzyme activities. Piperine treatment with carcinogens resulted in inhibition of thiobarbituric reactive substances. It mediated a significant increase in the GSH levels 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 changes by inhibiting lipid peroxidation and mediating enhanced synthesis or transport of GSH thereby replenishing thiol redox.
Khajuria
A
A
Manitoba Institute of Cell Biology, Winnipeg, Canada.
Thusu
N
N
Zutshi
U
U
Bedi
K L
KL
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000470:Alkaloids; D000818:Animals; D052117:Benzodioxoles; D002273:Carcinogens / Q000494:pharmacology*; D004791:Enzyme Inhibitors; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008748:Methylcholanthrene / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D004124:p-Dimethylaminoazobenzene / Q000494:pharmacology
D000470:Alkaloids; D052117:Benzodioxoles; D002273:Carcinogens; D004791:Enzyme Inhibitors; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D008748:Methylcholanthrene; D015127:9,10-Dimethyl-1,2-benzanthracene; D004124:p-Dimethylaminoazobenzene; D005723:gamma-Glutamyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; C008922:piperine