Modulatory effect of naringenin on N-methyl-N'-nitro-N-nitrosoguanidine- and saturated sodium chloride-induced gastric carcinogenesis in male Wistar rats.

Naringenin is a flavanone that is believed to have many biological actions, including as an anti-oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl) in rats. Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S-NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks. In Group II rats in which gastric cancer was inducted with MNNG and S-NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochrome b(5) and NADPH cytochrome c reductase, with concomitant decreases in the activity of the phase II enzymes glutathione S-transferase and UDP-glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels. These results indicate that naringenin has a chemopreventive action against MNNG-induced gastric carcinoma in experimental rats.