Prevention of N-nitrosodiethylamine-induced lung tumorigenesis by ellagic acid and quercetin in mice.
The polyphenolic antioxidants, consumed as an integral part of vegetables, fruits and beverages, are suggested as possessing anticarcinogenic properties. In the present study we have looked into the anticarcinogenic potential of plant polyphenols ellagic acid (EA) and quercetin against N-nitrosodiethylamine-induced lung tumorigenesis in mice. Ellagic acid was able to significantly reduce tumour incidence to 20% from the control value of 72.2%. Similarly, tumour burden was also decreased, although not significantly, from 3.15 to 2.5. Quercetin (QR) caused the tumour incidence to decrease from 76.4% to 44.4% when fed until the third dose of carcinogen. Both of the polyphenols suppressed the tumour incidence mainly by acting at the initiation phase of the carcinogenesis, since continuing the feeding of polyphenols until the termination of the experiment did not cause any apparent change in tumour incidence or tumour burden. Besides this, ellagic acid was found to be a better chemopreventor than quercetin. In order to search for their mechanism of action, the effect of feeding of these compounds on reduced glutathione (GSH), an important endogenous antioxidant, and on lipid peroxidation was investigated. Both ellagic acid and QR caused a significant increase in GSH and decrease in NADPH- and ascorbate-dependent lipid peroxidation. Ellagic acid was found to be more effective in decreasing the lipid peroxidation and increasing the GSH. This may be one of the reasons for its observed better anticarcinogenic property as compared to quercetin.
Department of Biophysics, Postgraduate Institute of Medical Education & Research, Chandigarh, India.
K L
KL
Khanduja
R K
RK
Gandhi
V
V
Pathania
N
N
Syal
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D018890:Chemoprevention; D004052:Diethylnitrosamine / Q000037:antagonists & inhibitors*; D004610:Ellagic Acid / Q000627:therapeutic use*; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008175:Lung Neoplasms / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D011794:Quercetin / Q000627:therapeutic use*
D016588:Anticarcinogenic Agents; D004610:Ellagic Acid; D004052:Diethylnitrosamine; D011794:Quercetin; D005978:Glutathione