Prevention of cancer remains a primary need and new chemopreventive agents must be developed for this purpose. Towards this goal, a chemoprevention study was conducted to evaluate the activity of resveratrol (Res), a phytoalexin, as an inhibitor of colon carcinogenesis. Wistar male rats were divided into six groups, group 1 were control rats, group 2 were control rats that received Res (8 mg/kg body wt p.o. everyday), rats in groups 3–6 were treated weekly with 1,2-dimethylhydrazine (DMH, 20 mg/kg body wt, s.c. × 15 times). In addition, groups 4, 5 and 6 received Res as in group 2. Modifying effects were assessed using aberrant crypt foci (ACF) and the extent of histopathological lesions as end point markers. At the end of 30 weeks, Res markedly reduced tumor incidence, the degree of histological lesions and also the size of tumors significantly ( P < 0.05) as compared with the rats treated with unsupplemented DMH. The number of ACF consisting of more than six aberrant crypts per rat was observed in group 6 (6.2 ± 1.4), group 5 (7.7 ± 1.0) and group 4 (8.2 ± 1.4) which were significantly lower than that of group 3 (22.3 ± 2.4) ( P < 0.05). The most pronounced inhibition of ACF development was noted in rats fed Res for the entire period and also during the post-initiation period. Also, Res administration lowered the number of argyrophilic nucleolar organizing region-associated proteins (AgNORs) per nucleus in non-lesional colonic crypts, which reflects the cell proliferation activity. Oxidative imbalance in DMH-treatment was significantly ( P < 0.01) modulated on Res supplementation as indicated by optimal concentration of thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT) and reduced glutathione (GSH). The results of our study suggest Res to be an effective chemopreventive agent, which suppresses DMH-induced colon carcinogenesis at various stages.

The aim of the study was to investigate the antiinflammatory effects of naringenin in rats induced liver damage by exposure to ethanol. Rats were divided into four groups, groups 1 and 2 received isocaloric glucose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were supplemented with naringenin (50 mg/kg p.o.) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, transforming growth factor-alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), macrophage inflammatory protein 2 (MIP-2) and CD14 in ethanol fed rats as compared to those of the control. Ethanol-fed rats exhibited increased staining for the presence of inducible nitric oxide (iNOS) protein adducts in the liver. Supplementation with naringenin for the last 30 days to ethanol-fed rats, significantly decreased the levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, TNF-α, IL-6, NF-κB, COX-2, MIP-2, CD14 and iNOS protein adducts in the liver as compared to the untreated ethanol fed rats. The inhibition of TNF-α, IL-6, NF-κB, COX-2, MIP-2, iNOS and CD14 by naringenin may contribute to its antiinflammatory activity in ethanol fed rats.

Diet-induced changes in the activities of bacterial enzymes are known to play a role in colon cancer development. Resveratrol has been implicated as a protective agent in carcinogenesis. In the present study, the effect of resveratrol on the activities of faecal and colonic biotransforming enzymes such as β-glucuronidase, β-glucosidase, β-galactosidase, mucinase, nitroreductase and faecal sulfatase activity was assessed. The total number of aberrant crypt foci and their distribution in the proximal, medial and distal colon were observed in 1,2-dimethylhydrazine (DMH)-induced rats (group 3) and other treatment groups (groups 4–6). DMH (0.02g/kg body weight) was given subcutaneously once a week for 15 consecutive weeks, and the experiment was terminated at 30 weeks. DMH-treated rats showed elevated levels of cancer-associated bacterial enzyme activities, whereas on resveratrol supplementation in three different regimens, rats showed lowered activities. Resveratrol supplementation throughout the experimental period (group 6) exerted a more pronounced effect (P<0·01) by modulating the development of aberrant crypt foci and the activities of bacterial enzymes than did the other treatment regimens (groups 4 and 5). Thus, the present results demonstrate the inhibitory effect of resveratrol on DMH-induced colon carcinogenesis in rats.