Veerasamy Vinothkumar

Chemopreventive efficacy of geraniol against 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis

Abstract The status of lipid peroxidation, antioxidants, and detoxification enzymes were used as biochemical end points to assess the chemopreventive potential of geraniol, a monoterpene, in 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Topical application of 0.5% DMBA in liquid paraffin, three times a week, for 14 weeks developed well-differentiated squamous cell carcinoma in the buccal pouch of golden Syrian hamsters. Although 100% tumor formation was noticed in hamsters treated with DMBA alone, intragastric administration of geraniol, at a dose of 250 mg/kg body weight (b.w.) to DMBA-treated hamster completely prevented the formation of oral tumors. Furthermore, geraniol significantly reduced lipid peroxidation by-products and improved the status of enzymatic and non-enzymatic antioxidants as well as modulated the status of phase I and phase II detoxification enzymes, favoring the excretion of carcinogenic metabolite, during DMBA-induced oral carcinogenesis. The present study concludes that the chemopreventive potential of geraniol relies on its anti-lipid peroxidative and antioxidant function as well as modulatory effects on phase I and II detoxification enzymes to excrete the carcinogenic metabolite, during DMBA-induced hamster buccal pouch carcinogenesis.

Berberine prevents 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis: a biochemical approach.

Chemoprevention, a novel and useful approach in experimental oncology, deals with the prevention, suppression, or inhibition of carcinogenesis using natural or synthetic entities. This study evaluated the chemopreventive potential of berberine on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis. Oral squamous cell carcinoma was developed in the buccal pouch of golden Syrian hamsters by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. Tumor incidence, tumor volume, tumor burden, phase I and phase II carcinogen detoxification agents, lipid peroxidation, antioxidant status, and histopathological changes were assessed in hamsters treated with DMBA alone and in DMBA+berberine-treated animals. Hundred percent tumor incidences with an imbalance in carcinogen-metabolizing enzymes and cellular redox status were observed in hamsters treated with DMBA alone. Oral administration of berberine at a dose of 75 mg/kg body weight (bw) to DMBA-treated hamsters completely prevented tumor incidence and restored the status of the above-mentioned biochemical markers. Berberine, a traditional drug from Southeast Asia, shows promising chemopreventive efficacy in hamster buccal pouch carcinogenesis.

Geraniol, a natural monoterpene, ameliorates hyperglycemia by attenuating the key enzymes of carbohydrate metabolism in streptozotocin-induced diabetic rats

Abstract Context: Geraniol, an acyclic monoterpene alcohol is found in medicinal plants, is used traditionally for several medical purposes including diabetes. Objectives: The present study evaluates the antihyperglycemic potential of geraniol on key enzymes of carbohydrate metabolism in streptozotocin (STZ)-induced diabetic rats. Materials and methods: Diabetes was induced in experimental rats, by a single intraperitoneal (i.p) injection of STZ [40 mg/kg body weight (b.w.)]. Different doses of geraniol (100, 200 and 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) were administrated orally to diabetic rats for 45 days. Body weight, food intake, plasma glucose, insulin, blood haemoglobin (Hb), glycosylated haemoglobin (HbA1c), hepatic glucose metabolic enzymes and glycogen were examined. Results: The LD50 value of geraniol is 3600 mg/kg b.w. at oral administration in rats. Administration of geraniol in a dose-dependent manner (100, 200, 400 mg/kg b.w.) and glyclazide (5 mg/kg b.w.) for 45 days significantly improved the levels of insulin, Hb and decreased plasma glucose, HbA1C in diabetic-treated rats. Geraniol at its effective dose (200 mg/kg b.w.) ameliorated the altered activities of carbohydrate metabolic enzymes near normal effects compared with two other doses (100 and 400 mg/kg b.w.). Geraniol treatment to diabetic rats improved hepatic glycogen content suggesting its anti-hyperglycemic potential. Geraniol supplement was found to preserve the normal histological appearance of hepatic cells and pancreatic β-cells in diabetic rats. Discussion and conclusions: The present findings suggest that geraniol can potentially ameliorate key enzymes of glucose metabolism in experimental diabetes even though clinical studies used to evaluate this possibility are warranted.

Anti-clastogenic potential of carnosic acid against 7,12-dimethylbenz(a) anthracene (DMBA)-induced clastogenesis

Carnosic acid, a primary phenolic compound found in the leaves of rosemary (Rosmarinus officinalis), has diverse pharmacological and biological activities. The aim of the present study was to investigate the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. The frequency of bone marrow micronucleated polychromatic erythrocytes (MnPCEs), chromosomal aberrations (cytogenetic end points), the status of Phase I and II detoxification enzymes, lipid peroxidation by-products and antioxidants (biochemical endpoints) were analyzed to assess the anti-clastogenic effect of carnosic acid in DMBA-induced clastogenesis. Oral pretreatment of carnosic acid for five days to DMBA-treated hamsters significantly protected DMBA-induced clastogenesis as well as biochemical abnormalities. Although the exact mechanism of anti-clastogenic effects of carnosic acid is unclear, the antioxidant potential and effect on modulation of Phase I and II detoxification enzymes could play a possible role.

Antidiabetogenic efficiency of menthol, improves glucose homeostasis and attenuates pancreatic β-cell apoptosis in streptozotocin–nicotinamide induced experimental rats through ameliorating glucose metabolic enzymes

The phytochemical, menthol, has been reported to play many beneficial roles. However, under diabetic conditions, there is no detail mechanism of its beneficial action in the glucose homeostasis. The present study, we investigated to explore the role of menthol, on the glucose metabolic enzymes and pancreatic islet cell apoptosis of streptozotocin-nicotinamide (STZ-NA) induced diabetes in rats. Diabetes was induced by single intraperitoneal (i.p.) injection of STZ (50mg/kg/b.w.) and NA (110mg/kg/b.w.). Diabetic rats were treated with different dose of menthol (25, 50, and 100mg/kg/b.w.) and glibenclamide (600μg/kg/b.w.) daily for 45 days. The result of our study shows that menthol significantly reduced the blood glucose and glycosylated hemoglobin levels and significantly increased the total hemoglobin, plasma insulin and liver glycogen levels in diabetic rats. The altered activities of hepatic glucose metabolic enzymes, serum biomarkers of liver damage were restored to near normal. The pathological abnormalities in hepatic and pancreatic islets of diabetic rats were significantly ameliorated by menthol intervention. These effects were mediated by suppressing pancreatic β-cells apoptosis and were associated with increased anti-apoptotic Bcl-2 expression and reduced pro-apoptotic Bax expression. Findings from the current study consent us to conclude that menthol alleviates STZ-NA-induced hyperglycemia via modulating glucose metabolizing enzymes, suppression of pancreatic β-cells apoptosis and altered hepatic, pancreatic morphology. This exclusivity and dearth of any noticeable adverse efficacy proposes the opportunity of using this monoterpene as an efficient adjuvant in the management diabetes mellitus.

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.

Betanin exhibits significant potential as an antihyperglycemic and attenuating the glycoprotein components in streptozotocin - nicotinamide induced experimental rats

Abstract This study hypothesized to evaluate the effect of betanin, a chromoalkaloid on plasma and altered tissues glycoprotein components in streptozotocin–nicotinamide-induced diabetic rats. Diabetes was induced by a single intraperitoneal (i.p.) injection of streptozotocin (45 mg/kg b.w.) dissolved in 0.1 M citrate buffer (pH 4.5) 15 min after the i.p. administration of nicotinamide (110 mg/kg b.w.). Experimental rats were administered betanin at the dose of 20 mg/kg b.w. and glibenclamide (600 µg/kg b.w.) once a day for 30 days. Diabetic rats revealed significant (p < 0.05) increase in the levels of glucose, HbA1C, hexose, hexosamine, sialic acid and fucose in the plasma; decrease in the levels of plasma insulin, Hb and sialic acid in the liver and kidney; significant (p < 0.05) increase in hexose, hexosamine and fucose in the liver and kidney. Moreover, periodic acid-Schiff staining of tissues revealed positive-stain accumulation in diabetic rats. On co-supplementation of betanin and glibenclamide to diabetic rats for the period of 30 days brought back the levels of plasma and tissues glycoprotein components. Based on the present study, we propose that betanin possesses significant protective effect on glycoprotein components in plasma and tissue of diabetic rats.

Allyl methyl sulfide, a garlic active component mitigates hyperglycemia by restoration of circulatory antioxidant status and attenuating glycoprotein components in streptozotocin-induced experimental rats

Abstract Diabetes is a major noncommunicable life-threatening chronic and pervasive condition that is consuming the world health in a petrifying rate. The circulatory system is one of the major sources of hyperglycemia-induced ROS generation. Historically, garlic has been revered as part of a healthful diet. Organosulfur compounds have been attributed to the medicinal properties and health benefits of garlic. The present study focuses on the ameliorative role of allyl methyl sulfide (AMS) in combating diabetic complications in diabetic rats. Male Wistar rats were randomly divided into four groups. Experimental diabetes was induced by a single intraperitoneal injection (i.p), of streptozotocin (STZ) (40 mg/kg b.w). STZ treated diabetic rats showed significant augment in plasma glucose level, lipidperoxidative (LPO) markers, glycoprotein components (hexose, hexosamine, sialic acid, and fucose), and significant decline in plasma insulin level, nonenzymatic antioxidants and activities of antioxidant enzymes in the circulatory system and tissues. Further, periodic acid-Schiff (PAS) staining of hepatic and renal tissues revealed positive stain accumulation and Western blot investigation of glucose transporter 2 (GLUT 2) in pancreas of STZ-induced hyperglycemic rats. Dietary intervention with AMS (100 mg/kg b.w) for 30 days demonstrated significant protective effects on all the biochemical parameters studied. Besides, biochemical findings were corroborated by histological exertion and Western blot study. The findings of current investigations recommended that AMS can ameliorate the consequences of diabetes due to their antioxidant efficacy and can be used as a potential therapeutic approach. Further studies are warranted to explore the clinical application of AMS.

Paeonol exhibits anti-tumor effects by apoptotic and anti-inflammatory activities in 7,12-dimethylbenz(a)anthracene induced oral carcinogenesis

ABSTRACT We investigated the preventive potential of paeonol on 7,12-dimethylbenz(a)anthracene (DMBA) induced oral carcinogenesis. Oral tumors were developed in the buccal pouches of Syrian golden hamsters using topical application of 0.5% DMBA three times/week for 10 weeks. DMBA treated hamsters developed hyperplasia, dysplasia and well-differentiated squamous cell carcinoma. The animals also exhibited increased lipid oxidation, decreased antioxidant status and altered levels of detoxification agents. Paeonol treatment of DMBA treated hamsters for 14 weeks decreased tumor incidence, volume and burden Paeonol treatment also increased antioxidant activity and decreased lipid oxidation to near normal levels. Histomorphology and the expression patterns of mutant p53, cyclo-oxygenase (COX-2) and caspase-9 were investigated in the oral buccal mucosa. Paeonol exhibited protective effects against DMBA induced oral carcinogenesis owing to its antitumor, antioxidant, anti-inflammatory and apoptosis inducing properties.

Allyl methyl sulfide, an organosulfur compound alleviates hyperglycemia mediated hepatic oxidative stress and inflammation in streptozotocin - induced experimental rats

Therapeutic approaches based on dietary compounds obtained from food products to handle diabetes involving oxidative stress and inflammation. Garlic is a common spice and has a long history as a folk remedy. Allyl methyl sulfide (AMS) is a potential garlic-derived organosulfur compound displaying a substantial range of optimistic actions in various diseases. Herein, we investigated the potential role of AMS in ameliorating the effects of oxidative stress and inflammation in the liver of streptozotocin (STZ)-induced experimental rats. Diabetes was induced by single intraperitoneal (i.p.) injection of STZ (40 mg/kg/b.w). STZ-induced hyperglycemic rats received daily intragastric doses of 50, 100 and 200 mg/kg/b.w of the AMS for 30 days. Dietary intervention of AMS (100 mg/kg b.w) resulted in significant attenuation in blood glucose and expression of pro-inflammatory markers TNF-α, IL-6, NF-κB p65 unit and significant elevation in the plasma insulin level. Moreover, AMS instigated a marked enhance in the levels of hepatic tissue non enzymatic antioxidants and the activities enzymatic antioxidants of diabetic rats with significant decline in lipid peroxides and hydroperoxides formation, serum biomarkers of liver damage, thus representing the protecting efficacy of AMS in hyperglycemic state. The pathological abnormalities in hepatic tissues of diabetic rats were significantly ameliorated by AMS supplementation and offered great support to the biochemical findings. These conclusions explicate the prospective use of AMS as a promising compound against glucotoxicity mediated hepatic oxidative dysfunction in rats. Clinical trials in validating this benefit for optimizing the AMS nutrition are however warranted.