ABSTRACT
With an aim to investigate the protective effect of Withaferin-A on 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis in Syrian golden hamsters, tumour incidence, tumour volume and tumour burden and status of detoxication agents, lipid peroxidation and antioxidants in DMBA administered (3 times/week for 14 weeks) hamsters were assessed. Hundred percent tumour formation in DMBA alone administered animal was observed. Oral administration of Withaferin-A (20 mg/kg body weight) to DMBA administered animals for 14 weeks completely prevented the tumour incidence, tumour volume and tumour burden. Also, Withaferin-A showed significant anti-lipid peroxidative and antioxidant properties and maintained the status of phase-I and phase-II detoxication agents during DMBA-induced oral carcinogenesis. The results thus indicate that the protective effect of Withaferin-A is probably due to its anti-lipid peroxidative and antioxidant functions as well as modulating effect on carcinogen detoxication during DMBA-induced oral carcinogenesis.
Subject(s)
Ergosterol/analogs & derivatives , Mouth Neoplasms/drug therapy , Phytotherapy , Protective Agents/therapeutic use , 9,10-Dimethyl-1,2-benzanthracene , Animals , Antioxidants/metabolism , Cricetinae , Drug Screening Assays, Antitumor , Ergosterol/chemistry , Ergosterol/pharmacology , Ergosterol/therapeutic use , Erythrocytes/drug effects , Erythrocytes/metabolism , Liver/drug effects , Liver/metabolism , Metabolic Detoxication, Phase I , Metabolic Detoxication, Phase II , Mouth Neoplasms/blood , Mouth Neoplasms/chemically induced , Protective Agents/chemistry , Protective Agents/pharmacology , Thiobarbituric Acid Reactive Substances/metabolism , WithanolidesABSTRACT
The present study has investigated the antigenotoxic effect of withaferin-A, a steroidal lactone obtained from the roots and leaves of Withania somnifera, in 7,12-dimethylbenz(a)anthracene (DMBA)-induced genotoxicity. Measurement of the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations is used as cytogenetic endpoints. A single intraperitoneal injection of DMBA (30 mg/kg b.w.) to golden Syrian hamsters resulted in marked elevation in the frequency of MnPCEs and aberrations in the chromosomal structure. Hamsters pretreated with withaferin-A intraperitonealy 2 h before the injection of DMBA, significantly reduced the frequency of MnPCEs and chromosomal aberrations such as chromosomal break, gap, minute, and fragment. Our results thus demonstrated the antigenotoxic effect of withaferin-A in DMBA-induced genotoxicity in the bone marrow of golden Syrian hamsters.
Subject(s)
9,10-Dimethyl-1,2-benzanthracene/antagonists & inhibitors , 9,10-Dimethyl-1,2-benzanthracene/toxicity , Antimutagenic Agents/pharmacology , Bone Marrow/drug effects , Ergosterol/analogs & derivatives , Mutagens/toxicity , Animals , Antimutagenic Agents/isolation & purification , Chromosome Aberrations/drug effects , Cricetinae , Ergosterol/isolation & purification , Ergosterol/pharmacology , Erythrocytes/drug effects , Male , Medicine, Ayurvedic , Mesocricetus , Micronuclei, Chromosome-Defective/drug effects , Micronucleus Tests , Withania/chemistry , WithanolidesABSTRACT
BACKGROUND & OBJECTIVE: Overproduction of lipid peroxidation byproducts and disturbances in antioxidant defense system have been implicated in the pathogenesis of several diseases including oral cancer. Though several studies have been done on the level of lipid peroxidation and antioxidants in oral cancer patients, there are no reports in patients with various clinical stages of oral squamous cell carcinoma. We carried out this study to assess the level of oxidative stress in oral cancer patients with various clinical stages. METHODS: Blood samples of 48 adult male oral cancer patients with various clinical stages of oral cancer (stage II to stage IV, 16 of each) and 16 age and sex matched healthy subjects were collected. Plasma and erythrocytes levels of thiobarbituric acid reactive substances (TBARS), vitamin E, reduced glutathione (GSH), and activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assayed using specific colorimetric methods. The statistical comparisons were performed by one way analysis of variance (ANOVA) followed by Student's t-test. RESULTS: Elevated lipid peroxidation and decline in non-enzymatic and enzymatic antioxidants status were noticed in oral cancer patients as compared to healthy subjects. The TBARS levels were gradually increased whereas antioxidants were gradually reduced from stage II to stage IV of oral cancer patients. INTERPRETATION & CONCLUSION: The altered lipid peroxidation in plasma and erythrocytes of oral cancer patients may be related to their compensatory changes in the antioxidants defense system.
