Madhavan Ramados Nirmal

Protective role of withaferin-A on 7,12-dimethylbenz(a)anthracene-induced genotoxicity in bone marrow of Syrian golden hamsters

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.

Antigenotoxic effect of genistein against 7,12-dimethylbenz[a]anthracene induced genotoxicity in bone marrow cells of female wistar rats

Carcinogen induced mutation in somatic cells leads to genetic instability, which is considered as an important facet of carcinogenesis. Agents that inhibit DNA adduct formation, stimulate DNA repair mechanisms, and possess antioxidant functions are considered as antigenotoxic agents. Genistein, the major isoflavone of soy products, protects animals against experimentally induced mammary and prostate cancers. 7,12-Dimethylbenz[a]anthracene (DMBA), a potent site-specific carcinogen, induce mutations in DNA through its active metabolite, dihydrodiol epoxide, what is a crucial step in cancer initiation. The antigenotoxic effect of genistein against DMBA-induced genotoxicity has been investigated in the present study by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations as cytogenetic end-points. The status of lipid peroxidation, antioxidants and detoxication agents were used as biochemical end-points to assess the antigenotoxic effect of genistein. Elevated MnPCEs frequency, marked chromosomal aberrations and enhanced status of lipid peroxidation, antioxidants and detoxication agents were observed in DMBA-treated animals. Oral pretreatment of genistein (20 mg/kg b.w.) for 5 days to DMBA-treated animals significantly reduced the frequency of micronucleus formation and chromosomal abnormalities as well as reversed the status of biochemical variables. Our results suggest that genistein has potent antigenotoxic effect against DMBA-induced genotoxicity.

Molecular effects of hesperetin, a citrus flavanone on7,12-dimethylbenz(a)anthracene induced buccal pouch squamous cell carcinoma in golden Syrian hamsters

Abstract In recent years, researchers have been focused on citrus flavanone, a naturally occurring bioactive substance of hesperetin. To investigate the molecular mechanism based chemopreventive efficacy of hesperetin on 7,12-dimethylbenz(a)anthracene (DMBA) induced hamster buccal pouch (HBP) squamous cell carcinoma (SCC). The oral tumour was provoked by painted with 0.5% DMBA on left buccal pouch thrice a week for 10 consecutive weeks developed well-differentiated SCC and tumour formation was 100% in DMBA alone. We evaluated the chemopreventive potential of hesperetin by assessing the lipid peroxidation (LPO) by-products, status of enzymatic, non-enzymatic antioxidants, detoxifying agents etc. Moreover, modulating expression of apoptotic and cell proliferation markers were observed in HBP SCC experimental hamsters. Oral administration of hesperetin (20 mg/kg b.w.) to DMBA painted hamsters significantly reversed the stages of oral SCC. Our findings indicate that hesperetin possesses a chemopreventive effect in DMBA-induced oral SCC by exerting anti-carcinogenic property.

Role of receptors of advanced glycation end-products (RAGE) in type 2 diabetic and non-diabetic individuals with chronic periodontal disease: an immunohistochemical study.

AIM   The relationship between diabetes and periodontal disease is well established. It has been shown that advanced glycation end-products might exert noxious effects on several tissues of the body through its receptor. Evidence for the role of receptors of advanced glycation end-products in periodontal disease for diabetes is limited, and their presence in human gingival tissues has been demonstrated in few studies. In this study, we demonstrate the presence of receptors of advanced glycation end-products in patients with chronic periodontitis, with and without type 2 diabetes. METHODS   Gingival biopsies from 19 patients with both type 2 diabetes and chronic periodontitis, and 18 healthy controls with chronic periodontitis, were immunohistochemically stained for receptors of advanced glycation end-products. RESULTS   On immunohistochemical analysis, positive staining for receptors of advanced glycation end-products was seen in the endothelium and the basal and spinous layers of the inflamed gingival epithelium in both type 2 diabetes and non-diabetes tissue, with a statistically-significant difference between both groups (P <0 .05). CONCLUSIONS   There was a significant difference in receptors of advanced glycation end-product immune reactivity between both groups. Receptors of advanced glycation end-product increase in type 2 diabetes gingival tissue might indicate possible involvement of this receptor in periodontal destruction in individuals with type 2 diabetes.