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1.
J Cancer Res Ther ; 14(6): 1379-1388, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30488860

RESUMEN

BACKGROUND: Colorectal cancer (CRC) is the second most diagnosed cancer often identified during the later stages of carcinogenesis. Orientin, a C-glycoside of luteolin, is well known for its versatile therapeutic action toward oxidative stress-induced cellular response may exert chemoprevention against CRC. MATERIALS AND METHODS: In our study, we investigated the modulatory effect of orientin on lipid peroxidation, antioxidant defense, and biotransforming bacterial enzymes in 1, 2-dimethylhydrazine (DMH)-induced male albino Wistar rats in a dose-dependent manner. Animals were induced with DMH (20 mg/kg b.wt) for 15 weeks and administered with orientin in three different doses (5 mg/kg, 10 mg/kg, and 20 mg/kg b. wt) daily under distinct phases (initiation, postinitiation, and the entire) for a total treatment period of 30 weeks. RESULTS: Orientin reinstates the alterations induced by DMH on lipid peroxidation and enzymatic antioxidants through its rich-free radical scavenging properties. In addition, orientin curtails the DMH-induced augmentation of biotransforming bacterial enzymes to inhibit the colon cancer progression. Overall, experimental findings suggest that orientin significantly inhibits the DMH induced colon cancer in all the three different doses, however, maximum inhibition was observed on supplementation of 10 mg/kg b.wt for the entire period of the study. CONCLUSION: Hence, the intraperitoneal administration of 10 mg/kg b.wt orientin for the entire period is recommended for further molecular investigation to elucidate the precise mechanism of inhibition and so orientin can be used as a novel chemotherapeutic agent for CRC.


Asunto(s)
1,2-Dimetilhidrazina/efectos adversos , Antioxidantes/metabolismo , Biotransformación/efectos de los fármacos , Carcinogénesis/efectos de los fármacos , Flavonoides/farmacología , Glucósidos/farmacología , Peroxidación de Lípido/efectos de los fármacos , Animales , Carcinogénesis/inducido químicamente , Carcinogénesis/metabolismo , Colon/efectos de los fármacos , Colon/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Modelos Animales de Enfermedad , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar
2.
Toxicol Rep ; 5: 977-987, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30319939

RESUMEN

Orientin, a c- glycosyl flavonoid found copiously in roobios tea and various medicinal plants is well known for its antioxidant, anti-inflammatory, and antitumor effects. The present study aims to investigate the anti-cancer efficacy of orientin on 1,2 dimethyl hydrazine induced colonic aberrant crypt foci (ACF) and cell proliferation in Wistar rats. Rats were randomly divided into six groups and fed with high fat diet. Group 1 left as untreated control. Group 2 administered with DMH (20 mg/kg body weight) for initial 4 weeks and left untreated. Group 3 received orientin (10 mg/kg body weight) alone for the entire period. Group 4 received orientin along with DMH for initial 4 weeks and left untreated; Group 5 administered DMH for initial 4 weeks and treated with orientin for remaining 12 weeks; Group 6 administered DMH and treated with orientin throughout the entire period. Our preclinical findings suggest that the administration of orientin decreases the occurrence of DMH induced colonic polyps and aberrant crypt foci, augments antioxidant defense and altered the activities of drug metabolizing phase I and phase II enzymes in colonic and hepatic tissues and thereby ensuring the detoxification of carcinogen. Furthermore, orientin attenuates the aberrant crypt foci formation and reinstates the DMH induced cell proliferation, as evident from the AgNORs staining of colonic tissues of experimental rats. Thus, our study emphasizes that orientin may prevent DMH induced precancerous lesions and proven to be a potent antioxidant and antiproliferative agent.

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