ABSTRACT
This study was carried out to investigate the chemopreventive potential of rosmarinic acid (RA) against 1,2-dimethylhydrazine (DMH) induced rat colon carcinogenesis by evaluating the effect of RA on tumour formation, antioxidant enzymes, cytochrome P450 content, p-nitrophenol hydroxylase and GST activities. Rats were divided into six groups and fed modified pellet diet for the entire experimental period. Group 1 served as control, group 2 received RA (10 mg/kgb.w.). Groups 3-6 were induced colon cancer by injecting DMH (20 mg/kgb.w.) subcutaneously once a week for the first four weeks (groups 3-6). In addition, RA was administered at the doses of 2.5, 5 and 10 mg/kgb.w. to groups 4-6 respectively. DMH treated rats showed large number of colonic tumours; decreased lipid peroxidation; decreased antioxidant status; elevated CYP450 content and PNPH activities; and decreased GST activity in the liver and colon. Supplementation with RA (5 mgkg/b.w.) to DMH treated rats significantly decreased the number of polyps (50%); reversed the markers of oxidative stress (21.0%); antioxidant status (38.55%); CYP450 content (29.41%); and PNPH activities (21.9%). RA at the dose of 5 mg/kgb.w. showed a most pronounced effect and could be used as a possible chemopreventive agent against colon cancer.
Subject(s)
Antineoplastic Agents/pharmacology , Cinnamates/pharmacology , Colonic Neoplasms/prevention & control , Depsides/pharmacology , 1,2-Dimethylhydrazine/toxicity , Animals , Antioxidants/pharmacology , Carcinogens/toxicity , Colonic Neoplasms/chemically induced , Dietary Supplements , Disease Models, Animal , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Rosmarinic AcidABSTRACT
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.
