Anticarcinogenic activity of meso-zeaxanthin in rodents and its possible mechanism of action.

Anticarcinogenic activity of meso-zeaxanthin (MZ), a xanthophyll carotenoid with profound antioxidant activity, was evaluated against 3-methylcholanthrene (3-MC)-induced sarcoma in mice. Oral administration of MZ at different doses significantly increased tumor latency period. In 3-MC control group, animals started developing sarcoma on 6th week. However animals treated with 3-MC and MZ (50 and 250 mg/kg b.wt) started developing sarcoma only on 15th and 18th week, respectively. Survival of tumor-bearing mice was significantly increased by MZ treatment. Animals in 3-MC control group started dying due to tumor burden from 8th week. All animals treated with MZ (50 and 250 mg/kg b.wt) along with 3-MC were found to be alive even after 16 and 20 wk, respectively. Oral administration of MZ inhibited different CYP450 isoenzymes like CYP1A1 (PROD), CYP1A2 (MROD), and CYP2B1/2 (EROD), which are involved in carcinogen metabolism in a dose-dependent manner. Moreover, levels of phase II enzymes like UDP-glucuronyl transferase and glutathione-S-transferase, which are involved in detoxification of carcinogens, were significantly increased by MZ treatment. Results indicated that mode of action of MZ may be through inhibition of carcinogen activation coupled with enhancement of detoxification process. MZ may also inhibit promotion phases of carcinogenesis by its antioxidant activity.

Amelioration of radiation-induced damages in mice by carotenoid meso-zeaxanthin.

PURPOSE: The present study was undertaken to evaluate the radioprotective effect of meso-zeaxanthin, a xanthophyll carotenoid with profound antioxidant activity. MATERIALS AND METHODS: Swiss albino mice were treated with different doses of meso-zeaxanthin (50 and 250 mg/kg body weight, orally) five days before irradiation and sacrificed at different time points. The protective effects of meso-zeaxanthin on mortality, haematological parameters, bone marrow cellularity and gastrointestinal system of irradiated mice were studied. The anti-genotoxic action of meso-zeaxanthin was studied by measuring micronuclei formation, chromosomal aberrations and DNA damage (comet assay). RESULTS: Meso-zeaxanthin administration significantly increased the lifespan of irradiated mice and reduced myelosuppression as evident from increases in white blood cell counts, bone marrow cellularity and the number of maturing monocytes when compared to the myelosuppression in radiation control animals. Meso-zeaxanthin significantly elevated the radiation-induced reduction in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione in both liver and intestinal mucosa. The carotenoid-treated animals showed a profound reduction in genotoxic activity which was apparent in decreases in micronuclei formation and chromosomal aberrations. Irradiation also induced damage to cellular DNA as was obvious from increases in comet parameters like tail DNA%, tail moment, tail length and Olive tail moment in the radiation control group. These parameters were decreased by meso-zeaxanthin treatment. CONCLUSION: Results indicated a radioprotective potential of meso-zeaxanthin.

Effect of carotenoid lutein on N-nitrosodiethylamine-induced hepatocellular carcinoma and its mechanism of action.

Oxycarotenoid lutein (3,3'-dihydroxy-ß,ε-carotene) was checked for anticarcinogenic activity against N-nitrosodiethylamine-induced hepatocellular carcinoma (HCC) in rats. Lutein could significantly reduce the altered morphological and pathological changes in the liver induced by N-nitrosodiethylamine. Biochemical analysis of serum and tissues indicated that alanine transaminase, aspartate transaminase, and alkaline phosphatase were significantly elevated in the control group and significantly reduced in the lutein-treated groups. These enzymes in liver tissue, which were found to be elevated in the control group, were significantly reduced in the lutein-treated groups. Glutathione level was low in the control groups and it was found to be increased in the treated groups. The activity of γ-glutamyl transpeptidase, a marker of cellular proliferation, was found to be significantly elevated in both the serum and the liver in the control group, which was reduced by the administration of lutein. Studies on the mechanism of action of lutein have indicated that it could significantly inhibit cytochrome P450 enzymes in vitro and in vivo in rats. Moreover, lutein could enhance the detoxifying enzymes glutathione-S-transferase and UDP glucuronyl transferase in vivo. Inhibition of carcinogenesis by lutein could be because of a combined effect of its antioxidant activity along with the inhibition of cytochrome P450 enzymes and inducing detoxifying enzymes. Lutein is nontoxic and is one of the prime compounds in the chemoprevention trials of the future.

Anti-mutagenic and anti-carcinogenic potential of the carotenoid meso-zeaxanthin.

Meso-zeaxanthin was investigated for antimutagenic and anticarcinogenic activity, using the Ames test (Salmonella typhimurium strains TA 98, TA 100, TA 102 and TA 1535) with direct acting mutagens like sodium azide (NaN3) (5 µg/ plate), nitro-o-phenylendiamin (NPD) (20 µg/ plate), N-methyl- N'-nitro-N-nitrosoguanidine (MNNG) (1µg/ plate) and tobacco extract 50 mg/ plate) and with a mutagen needing microsomal activation, acetamidofluorene (AAF) ( 20 µg/ plate). The carotenoid was found to inhibit the mutagenicity induced by NaN3, NPD and MNNG in a concentration dependent manner, as well as that with AAF and the tobacco extract. Concentrations needed for 50 % inhibiton was found to be 50 µg/ plate for the chemical mutagens and 100 µg/ plate for tobacco extract. Using specific resorufin derivatives as substrates in vitro, the concentration of meso-zeaxanthin needed for 50 % inhibition of CYP1A2 (7-methoxyresorufin-O-demethylase) was 5 µg/ml, for CYP2B 1/2 (7- pentoxyresorufin-O-depentylase) was 8 µg/ml and for CYP1A1 (7-ethoxyresorufin-O-deethylase) was 12 µg/ml, while that of CYP 2E1 (aniline hydroxylase) was 7µg/ml and for CYP 1A, 2A, 2B, 2D and 3A (aminopyrene-N-demethylase) was 10.5 µg/ml. Evaluated using nitroso diethyl amine (NDEA) induced hepatocellular carcinoma in rats, treatment with meso-zeaxanthin reduced the tumor incidence when compared to the control group. The activity of glutamate oxaloacetate transaminase, glutamate pyruvate transaminase and alkaline phosphatase was drastically elevated in both serum and liver tissue of NDEA alone treated control animals and meso-Zeaxanthin pretreated animals showed significant decrease to normal levels, in line with histopathological findings.