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Periodontitis is a chronic inflammatory disease, caused by interaction between periodontopathic bacteria and the host immune response. MicroRNAs are small, single-stranded molecules, which play a key role in the regulation of diverse biological processes. Dysregulation of microRNAs function can lead to several diseases such as autoimmune and chronic inflammatory diseases. The objective of the study was to determine the association between selected single nucleotide polymorphisms in miR-125a, miR-499 and LIN28 homology A with chronic periodontitis susceptibility in a sample population from south India. Genotyping of the single nucleotide polymorphisms in miR-125a (rs41275794, rs12976445, rs10404453 and rs12975333), miR-499 (rs3746444) and LIN28 homolog A (rs3811463) was performed in DNA from288 controls (individuals with healthy gingiva) and 262 cases (chronic periodontitis patients) by direct dye-terminator sequencing. Disease association analysis revealed a significant association of the variant alleles of the miR-499a polymorphism (rs3746444) in chronic periodontitis [OR = 2.07; 95%CI (1.35–3.17)]. The risk associated C-allele frequency was found to be higher in chronic periodontitis subjects as compared to that of healthy individuals. Similar results were also observed in the dominant model [OR = 2.42; 95% CI (1.67–3.51)]. The recessive model for miR-125a polymorphism (rs12976445) was also found to be statistically significant with OR = 1.54 and 95% CI (1.03–2.30). The haplotype “GCGGCA” was found to be higher in chronic periodontitis subjects than in healthy individuals. Pairwise linkage disequilibrium analysis exhibited that the polymorphisms, rs41275794 and rs12976445 in miR-125a, were in strong linkage equilibrium (D′ = 0.97). Epistatic interaction by multifactorial dimensionality reduction analysis revealed that the genotypes of the polymorphisms of miR-125a (rs41275794, rs12976445, rs10404453), miR-499a (rs3746444) and LIN28 (rs3811463) were interacting significantly [OR = 2.54 (1.65–3.92)], thereby contributing to the risk of chronic periodontitis.

Diabetes mellitus is associated with dyslipidemia, which is a significant risk factor for cardiovascular complications. The present study was carried out to evaluate the effects of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) alone and in combination on alterations in lipids, lipoproteins and enzymes involved in lipid metabolism in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. A significant (p

The present study was undertaken to investigate the protective effect of tetrahydrocurcumin (THC) and chlorogenic acid (CGA) against streptozotocin (STZ)–nicotinamide (NA)-induced type 2 diabetes in adult Wistar rats. Diabetes was induced in experimental rats weighing 180–220 g, by a single intraperitoneal (i.p.) injection of STZ (45 mg/kg BW), 15 min after the (i.p.) administration of NA (110 mg/kg BW). THC (80 mg/kg BW) and CGA (5 mg/kg BW) were orally administered to diabetic rats for a period of 45 days. Fasting plasma glucose, glycosylated haemoglobin (HbA 1C ), thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH) were significantly increased, whereas insulin, total haemoglobin (Hb), non-enzymic antioxidants (reduced glutathione (GSH), vitamin C, vitamin E and ceruloplasmin) were decreased significantly in diabetic rats. Though the diabetic rats treated with THC and CGA individual exerts beneficial effects in all the biochemical parameters in (STZ)-induced diabetic rats. The combined treatment with THC and CGA normalized all the above-mentioned biochemical parameters in STZ-induced diabetic rats. Normal pancreatic histological architecture in THC and CGA treated diabetic rats revealed that these phytochemical exert higher degree of protection when administered in combination than single treatment of individual compounds.

The present study aimed to evaluate the radioprotective effect of lycopene, a naturally occurring dietary carotenoid on gamma-radiation-induced toxicity. The cellular changes were estimated by using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH). The DNA damage was analyzed by cytokinesis blocked micronucleus assay (CBMN), dicentric aberration (DC) and translocation frequency. The gamma-radiation at different doses (1, 2 and 4Gy) resulted in a significant increase in the number of micronuclei (MN), DC, translocation frequency, TBARS and HP level, whereas the levels of GSH and antioxidant enzymes were significantly decreased when compared with normal control. The maximum damage to lymphocytes was observed at 4Gy irradiation. Lycopene pretreatment (1, 5 and 10microg/ml) significantly decreased the frequency of MN, DC and translocation when compared with gamma-radiation control. The levels of TBARS, HP were also decreased and activities of SOD, CAT and GPx were significantly increased along with GSH levels when compared with gamma-radiation control. The dose of 5microg/ml of lycopene was found to be more effective than the other two doses. Thus, our result shows that pretreatment with lycopene offers protection to normal lymphocytes against gamma-radiation-induced cellular damage.

The present study was aimed to evaluate the radioprotective efficacy of hesperidin (HN), a flavonone glycoside against gamma-radiation-induced cellular damage in cultured human peripheral blood lymphocytes. Different concentrations of HN (3.27, 6.55, 9.83, 13.10, 16.38 and 19.65 microM) were pre-incubated with lymphocytes for 30 min prior to gamma-irradiation [4 Gy] and the micronuclei (MN) scoring, dicentric aberration and comet assay were performed to fix the effective dose of HN against gamma-irradiation induced cellular damage. The results indicated that among all the concentrations, 16.38 microM concentration of HN showed optimum protection by effectively decreasing the MN frequencies, dicentric aberrations and comet attributes. Based on the above results, 16.38 microM concentration of HN was fixed as the effective dose to further investigate its radioprotective efficacy which was then carried out by pre-incubating lymphocytes with 16.38 microM concentration of HN, exposing the lymphocytes to different doses (1, 2, 3 and 4 Gy) of radiation and investigating radiation induced genetic damage (MN, dicentric aberration, comet assay, DNA fragmentation assay) and biochemical changes (changes in the level of enzymic and non-enzymic antioxidants, lipid peroxidation). The results indicated a dose dependent increase in both genetic damage and thiobarbituric acid reactive substances (TBARS), accompanied by a significant decrease in the antioxidant status compared to HN treated groups which modulated the toxic effects through its antioxidant potential. Thus the current study shows HN to be an effective radioprotector against gamma-radiation induced in-vitro cellular damage in lymphocytes.

We investigated the radioprotective efficacy of quercetin (QN), a naturally occurring flavonoid against gamma radiation-induced damage in human peripheral blood lymphocytes and plasmid DNA. In plasmid study, QN at different concentrations (3, 6, 12, 24 and 48 microM) were pre-incubated with plasmid DNA for 1h followed by exposure of 6 Gy radiation. Among all concentrations of QN used, 24 microM showed optimum radioprotective potential. To establish the most effective protective concentration of QN in lymphocytes, the cells were pre-incubated with 3, 6, 12, 24 and 48 microM of QN for 30 min and then exposed to 4 Gy gamma-radiation. The concentration-dependent effects of QN were evaluated by scoring micronuclei (MN) frequencies. The results showed that QN decreased the MN frequencies dose dependently, but the effect was more pronounced at 24 microM. Thus, 24 microM of QN was selected as the optimum concentration and was further used to evaluate its radioprotective effect in lymphocytes. For that a separate experiment was carried out, in which lymphocytes were incubated with QN (24 microM) for 30 min and exposed to different doses of radiation (1, 2, 3 and 4 Gy). Genetic damage (MN, dicentric aberration and comet attributes) and biochemical changes were measured to evaluate the effect of QN on gamma-radiations (1-4 Gy). Radiation exposed showed significant increases in the genetic damage and thiobarbituric acid reactive substances (TBARS) accompanied by a significant decrease in the antioxidant status. QN pretreatment significantly decreased the genetic damage and TBARS and improved antioxidant status through its antioxidant potential. Altogether, our findings encourage further mechanistic and in vivo studies to investigate radioprotective efficacy of QN.

We examined the effect of ferulic acid (FA), a naturally occurring phenolic compound on lipid peroxidation and endogenous antioxidant status, DNA damage and inflammation in nicotine-administered Wistar rats. The effect of FA against nicotine toxicity was compared with N-acetylcysteine (NAC), a well-known antioxidant. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5mg/kg body weight (5 days a week, for 22 weeks) and FA and NAC were given simultaneously by intragastric intubation for 22 weeks. Seventy two Wistar rats were divided into six groups: (i) control, (ii) nicotine, (iii) nicotine+FA (iv), nicotine+NAC, (v) FA and (vi) NAC. At the end of the experimental period, cellular damage was assessed by measuring the activities of lactate dehydrogenase and alkaline phosphatase in plasma, which were significantly elevated in nicotine-administered rats when compared with control group. Enhanced lipid peroxidation (evaluated by measuring the thiobarbituric acid reactive substances and hydroperoxides) was accompanied by a significant decrease in the endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione in circulation, lung and liver of nicotine-treated rats when compared with control group. DNA single strand breaks (evaluated by comet assay) and frequency of micronuclei were significantly increased in peripheral blood of nicotine-treated rats when compared with control. Our Western blot analysis showed a significant increase in the expression of cyclooxygenase-2 and NF-kappaB in lung and liver of nicotine-treated rats. FA and NAC co-treated rats showed a significant decrease in the activities of circulatory lactate dehydrogenase and alkaline phosphatase, the levels of lipid peroxidative markers (in circulation, lung and liver), DNA single stranded breaks (comet parameters), micronuclei frequency (in the whole blood) and expression of cyclooxygenase-2 and Nf-kappaB (in lung and liver tissues), and significant increase in antioxidant status (in circulation, lung and liver). The protection of FA against nicotine-induced toxicity was merely equal to the effect of NAC. FA and NAC treatment alone did not produce any damage to control rats. Thus, we propose that FA exerts protective effect against nicotine toxicity by modulating the lipid peroxidation, inflammation, DNA damage and endogenous antioxidant status.

We have investigated the protective effect of quercetin (QN) against nicotine-induced prooxidant and antioxidant imbalance in circulation, lung, liver and kidney of experimental rats. The protective effect of QN was compared with N-acetylcysteine (NAC), a well-known antioxidant. Male albino rats of Wistar stain were used for the experimental study. Lung toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg body weight (5 days a week, for 22 weeks) and QN was given simultaneously by intragastric intubations for 22 weeks. The body weight gain of rats during experimental period was significantly decreased in nicotine treated group, whereas QN co-treated rats significantly increased in their body weight. The levels of lipid peroxidative indices viz., thiobarbituric acid reactive substances and hydroperoxides, and nitric oxide in circulation, lung, liver and kidney of nicotine-treated rats were increased significantly when compared to normal, which were brought down to near normal in QN co-treated group. Endogenous antioxidant status viz., superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione were found to be significantly decreased in circulation, lung, liver and kidney of nicotine-treated group, which were significantly increased in QN-administered groups. The extent of DNA damage (evaluated by comet assay) was significantly increased in circulatory blood of nicotine-treated rats, which was effectively brought down by QN treatment. The protective effect of QN against nicotine toxicity was comparable to that of NAC. Our data suggest that QN exerts its protective effect by modulating the extent of lipid peroxidation and augmenting antioxidant defense system and thus protects the DNA in experimental animals.

UV-B induces lipid peroxidation and oxidative stress in mammalian cells by producing reactive oxygen species. In this present study, we report the protective effect of ferulic acid (FA; 3-methoxy-4-hydroxycinnamic acid), a dietary antioxidant, on UV-B–induced oxidative stress and lipid peroxidation using normal human lymphocytes. Treatment of the human peripheral lymphocytes with UV-B irradiation caused a significant (P b .05) depletion of reduced glutathione (GSH) levels, superoxide dismutase, catalase, and GSH peroxidase activities, and increased the levels of thiobarbituric acid–reactive substances. Treatment of human lymphocytes with FA before 30 minutes of irradiation inhibited UV-B–induced lipid peroxidation. Ferulic acid also inhibited UV-B–induced depletion of antioxidant defense components, such as GSH peroxidase, catalase, superoxide dismutase, and GSH. The maximum dose of FA (10 μg/mL) normalized the UV-B–induced oxidative stress, indicating the protective effect of FA in human peripheral lymphocytes under in vitro conditions against UV-B exposure. Our observations suggest that FA reduces UV-B–induced lipid peroxidation and enhances antioxidant status in human lymphocytes exposed to UV-B radiation, and therefore, FA could serve as a protector against the UV-B–induced pathologic changes. © 2007 Elsevier Inc. All rights reserved.

Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant in the cells, which is suggested to culminate in cell death. The present work was aimed to evaluate the radioprotective effect of curcumin, a yellow pigment of turmeric on γ-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), ceruloplasmin, vitamins A, E and C and uric acid. The comet assay is a sensitive and rapid technique for quantifying and analyzing DNA damage in individual cells was exposed under γ-radiation. The increase in the severity of DNA damage was observed with the increase dose (1, 2 and 4Gy) of γ-radiation in cultured hepatocytes. TBARS were increased significantly, whereas the levels of GSH, vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in γ-irradiated hepatocytes. The maximum damage to hepatocytes was observed at 4Gy irradiation. On pretreatment with curcumin (1, 5 and 10μg/ml) showed a significant decrease in the levels of TBARS and DNA damage. The antioxidant enzymes were increased significantly along with the levels of GSH, vitamins A, E and C, uric acid and ceruloplamin. The maximum protection of hepatocytes was observed at 10μg/ml of curcumin pretreatment. Thus, pretreatment with curcumin helps in protecting the hepatocytes against γ-radiation-induced cellular damage and can be developed as an effective radioprotector during radiotherapy in near future.

Accumulating evidence on constitutive expression of cyclooxygenase-2 (COX-2), one of the isoforms of enzyme cyclooxygenase (COX) the other isoform being cyclooxygenase-1 (COX-1), questions the safety profile of non-steroidal anti-inflammatory drugs (NSAIDs). This COX-2 isoform which is induced not only during inflammation but also by factors such as cytokines, steroid hormones and mitogenic stimuli is constitutively expressed in brain, kidney and reproductive organs. Present NSAIDs, particularly COX-2 inhibitors is no longer considered safe since suppression of COX-2 in tissues which it is constitutively expressed may lead to adverse effects. Though intense expression of COX-2 in vas deferens is proved, lack of information with respect to its function has attracted a wide scope for research as to whether COX-2 in vas deferens contributes to male fertility. In the present study, the authors investigated the localization of COX-2 as well as COX-1 in mice vas deferens and also assessed the activity of COX-2 and total prostaglandin (PG) levels in vas deferens. Further they suppressed the expression of COX-2 using a preferential COX-2 inhibitor nimesulide and analyzed the sperm from vas deferens for any defects. COX-2 was intensely expressed in the epithelial cells of mice vas deferens and nimesulide was able to effectively suppress most of COX-2 expression. A decrease in PG levels was observed initially but interestingly, the levels tend to rise on sustained suppression of COX-2. The motility of sperm was affected severely after 6 h of nimesulide administration that suggested a crucial role of COX-2 towards fertility of mice sperm.

This report demonstrates that mice deficient in Flt-1 failed to establish ischemic preconditioning (PC)-mediated cardioprotection in isolated working buffer-perfused ischemic/reperfused (I/R) hearts compared to wild type (WT) subjected to the same PC protocol. WT and Flt-1+/- mice were divided into four groups: (1) WT I/R, (2) WT + PC, (3) Flt-1+/- I/R, and (4) Flt-1+/- + PC. Group 1 and 3 mice were subjected to 30 min of ischemia followed by 2 h of reperfusion and group 2 and 4 mice were subjected to four episodes of 4-min global ischemia followed by 6 min of reperfusion before ischemia/reperfusion. For both wild-type and Flt-1+/- mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the knockout mice was less compared to the WT mice even in preconditioning. The myocardial infarction and apoptosis were higher in Flt-1+/- compared to wild-type I/R. Flt-1+/- KO mice demonstrated pronounced inhibition of the expression of iNOS, p-AKT & p-eNOS. Significant inhibition of STAT3 & CREB were also observed along with the inhibition of HO-1 mRNA. Results demonstrate that Flt-1+/- mouse hearts are more susceptible to ischemia/reperfusion injury and also document that preconditioning is not as effective as found in WT and therefore suggest the importance of VEGF/Flt-1 signaling in ischemic/reperfused myocardium.

Hypercholesterolemia (HC) is a common health problem that significantly increases risk of cardiovascular disease. Both statin (S) and resveratrol (R) demonstrated cardioprotection through nitric oxide-dependent mechanism. Therefore, the present study was undertaken to determine whether combination therapy with statin and resveratrol is more cardioprotective than individual treatment groups in ischemic rat heart model. The rats were fed with 2% high cholesterol diet and after 8 weeks of high cholesterol diet the animals were treated with statin (1 mg/kg bw/day) and resveratrol (20 mg/kg bw/day) for 2 weeks. The rats were assigned to: (1) Control (C), (2) HC, (3) HCR, (4) HCS and (5) HCRS. The hearts, subjected to 30-min global ischemia followed by 120-min reperfusion were used as experimental model. The left ventricular functional recovery (+dp/dt(max)) was found to be significantly better in the HCRS (1926+/-43), HCR (1556+/-65) and HCS (1635+/-40) compared to HC group (1127+/-16). The infarct sizes in the HCRS, HCS and HCR groups were 37+/-3.6, 43+/-3.3 and 44+/-4.2 respectively compared to 53+/-4.6 in HC. The lipid level was found to be decreased in all the treatment groups when compared to HC more significantly in HCS and HCRS groups when compared to HCR. Increased phosphorylation of Akt and eNOS was also observed in all the treatment groups resulting in decreased extent of cardiomyocyte apoptosis but the extent of reduction in apoptosis was more significant in HCRS group compared to all other groups. In vivo rat myocardial infarction (MI) model subjected to 1 week of permanent left descending coronary artery (LAD) occlusion documented increased capillary density in HCR and HCRS treated group when compared to HCS treatment group. We also documented increased beta-catenin translocation and increased VEGF mRNA expression in all treatment groups. Thus, we conclude that the acute as well as chronic protection afforded by combination treatment with statin and resveratrol may be due to pro-angiogenic, anti-hyperlipidemic and anti-apoptotic effects and long-term effects may be caused by increased neo-vascularization of the MI zone leading to less ventricular remodeling.

Ionizing radiation is known to induce oxidative stress through generation of reactive oxygen species (ROS) resulting in imbalance of the pro-oxidant and antioxidant activities ultimately resulting in cell death. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn, and ricebran. FA exhibit a wide range of pharmacological effects including antiageing, anti-inflammatory, anticancer, antidiabetic, antiapoptotic, and neuroprotective. The present work is aimed at evaluating the radioprotective effect of FA, on gamma-radiation induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The cellular changes were estimated using lipid peroxidative indices like thiobarbituric acid reactive substances (TBARS), the antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH), ceruloplasmin, Vitamins A, E and C and uric acid. DNA damage was analyzed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with increasing dose (1, 2 and 4Gy) of gamma-radiation in cultured hepatocytes. TBARS were increased significantly, whereas the levels of GSH, Vitamins C, E and A, ceruloplasmin, uric acid and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy irradiation. Pretreatment with FA (1, 5 and 10 microg/ml) significantly decrease the levels of TBARS and DNA damage. In addition, pretreatment with FA significantly increased antioxidant enzymes, GSH, Vitamins A, E and C, uric acid and ceruloplasmin levels. The maximum protection of hepatocytes was observed at 10 microg/ml of FA pretreatment. Thus, pretreatment with FA helps in protecting the hepatocytes against gamma-radiation induced cellular damage and can be developed as a effective radioprotector during radiotherapy.

In this study we examined radioprotective effect of ferulic acid (FA) on gamma radiation-induced dicentric aberration and lipid peroxidation with reference to alterations in cellular antioxidant status in cultured lymphocytes. To establish most effective protective support we used three different concentrations of FA (1, 5 and 10 microg/ml) and three different doses of gamma-radiation (1, 2 and 4 Gy). Treatment of lymphocytes with FA alone (at 10 microg/ml) gave no significant change in micronuclei (MN), dicentric aberration (DC), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) or glutathione peroxidase (GPx) activities when compared with normal lymphocytes; irradiation at 1, 2 and 4 Gy increased the MN and DC frequencies in a dose-dependent manner. Treatment with FA for 30 min before radiation exposure resulted in a significant decline of MN and DC yields as FA concentration increased. Compared to 1 Gy exposure alone, the extent to which FA (1 microg/ml) reduced the MN and DC yields was 75% and 50%, respectively. With 4 Gy irradiation, FA (10 microg/ml) decreased 45% MN and 25% DC frequencies. FA-pretreated lymphocytes (1, 5 and 10 microg/ml) showed progressively decreased TBARS levels after irradiation. Irradiation (1, 2 and 4 Gy) significantly decreased GSH levels, SOD, CAT and GPx activities in a dose-dependent manner. Pretreatment with 10 microg/ml of FA significantly (p0.05) prevented the decreases in the radiation-induced GSH, SOD, CAT and GPx activities. These findings suggest potential use and benefit of FA as a radioprotector.

Background Diabetes mellitus is one of the most common endocrine disorders. A large number of studies are in progress to identify natural substances that are effective in reducing the severity of diabetes. Although a number of drugs are currently marketed, their long-term use can cause a number of adverse effects. Materials and methods In the present study, we examined the effect of photo-irradiated curcumin on experimental diabetes in order to evaluate the antihyperglycaemic effects of this compound on streptozotocin (40 mg/kg bodyweight)-induced diabetes. Photo-irradiated curcumin was given at a dose of 10, 30 and 80 mg/kg bodyweight. The level of blood glucose was elevated in the diabetic animals. The liver, kidney and brain were assayed for the degree of lipid peroxidation, reduced glutathione content and the activity of enzymic and levels of non-enzymic antioxidants. Results Antioxidant status decreased in the diabetic animals. Oral administration of photo-irradiated curcumin for 45 days resulted in a significant decrease in the levels of blood glucose, together with near normalisation of enzymic activity and the markers of lipid peroxidation. The best results were obtained in rats treated with 30 mg/kg bodyweight of photo-irradiated curcumin.

Background: Colon cancer is one of the most common forms of malignant tumors in humans, and its incidence is increasing. Since the intestinal microflora is directly in contact with the colonic cells, the enzymes of the bacterial microflora may also play a role in colon carcinogenesis. We studied the activity of bacterial enzymes in experimental colon cancer. Methods: Twenty milligrams per kilogram body weight of 1,2-dimethyl hydrazine (DMH) was administered subcutaneously once a week for first 15 weeks and then discontinued. Coconut cake (25%) was mixed in the diet and given to 30 rats to study the diet effect throughout the experimental period. After 30 weeks, the macroscopic findings in the colon as well as the incidence of tumors in 30 rats was recorded in each group and the activity of β-glucuronidase and mucinase was estimated in the tissues, colon and fecal contents of 10 rats per group. Results: Average number of tumors in the colon as well as the incidence of cancer was significantly increased in DMH-treated rats which was markedly reduced on supplementing coconut cake. DMH injections significantly elevated both the activities of β-glucuronidase (distal colon, distal intestine, liver and colon contents) and mucinase (colon and fecal contents) as compared to the control rats. The increase in β-glucuronidase activity may augment the hydrolysis of glucuronide conjugates, liberating the toxins, while the increase in mucinase activity may enhance the hydrolysis of the protective mucins in the colon. Coconut cake supplementation to DMH-treated rats significantly decreased the incidence and number of tumors as well as the activity of β-glucuronidase and mucinase. Conclusions: Coconut cake has a protective effect against DMH induced colon cancer by virtue of its ability to lower the activities of the microbial enzymes β-glucuronidase and mucinase.

The present study was undertaken to evaluate the potential role of curcumin, the antioxidant principal from Curcuma longa Linn., and the sulphur-containing amino acid N-acetylcysteine against ethanol-induced changes in the levels of prostanoids. Biochemical assessment of liver damage was done by measuring the activities of serum enzymes (i.e., aspartate transaminase and alkaline phosphatase), which were significantly increased in rats fed ethanol, whereas the elevated levels of these enzymes were decreased after curcumin and N-acetylcysteine treatment to rats fed ethanol. We observed a significant increase in the levels of prostaglandins E(1), E(2), F(2alpha), and D(2) in liver, kidney, and brain. Administration of curcumin and N-acetylcysteine was shown to decrease the level of these prostanoids in the tissue studied.

The effects of chronic zinc supplementation to Wistar rats at two doses (elemental) 50mg/g of diet (group-I) and 400mg/g of diet (group-II) on (i) lipid peroxidation status, superoxide dismutase activity, iron, and ceruloplasmin levels and (ii) circadian oscillations of glucose, total protein, alkalinephosphatase activity and thiobarbituric acid reactive substances were investigated. Iron in tissues (liver & kidney), ceruloplasmin, thiobarbituric acid reactive substances in plasma and tissues were found to be decreased in zinc supplemented groups. Superoxide dismutase activity in liver of group-I animals was increased but slightly decreased in group-II animals. Zinc might competitively inhibit the iron uptake by ferritin thereby reducing their levels. The increased activity of superoxide dismutase (in group I) might be due to induction/stabilisation of the enzyme by zinc. Induction of metallothionein and modulation of iron and copper levels during zinc supplementation might lead to low levels of lipid peroxidation. The peak time of circadian oscillation of total protein was delayed by three hours (during zinc supplementation). This might be due to altered positive or negative balance between synthesis and degradation of protein during zinc supplementation.

Chronic ingestion of ethanol for 60 days was known to alter the characteristics of biochemical circadian rhythms in Wistar rats. Peak times of glucose, potassium and lactic acid rhythms were delayed by 18 h, 3 h, and 3 h respectively, whereas peak times of cholesterol and malondialdehyde rhythms were advanced by 3 h and 9 h respectively during ethanol treatment. Significant changes in range (p < 0.001 expect in calcium) and 24 h mean (p < 0.001) of all the biochemical circadian rhythms studied were observed during ethanol treatment. The alterations in the characteristics of these biochemical circadian rhythms could be principally due to the alterations on the hepatic cellular architecture; other plausible underlying reasons are also discussed.

We made an attempt to study the antioxidant properties of Tinospora cordifolia roots, an indigenous plant used in Ayurvedic medicine in India in alloxan diabetic rats. Oral administration of an aqueous T. cordifolia root extract (TCREt) (2.5 and 5.0 g/kg) for 6 weeks resulted in a decrease in the levels of plasma thiobarbituric acid reactive substances, ceruloplasmin and alpha-tocopherol in alloxan diabetic rats. The root extract also causes an increase in the levels of glutathione and vitamin C in alloxan diabetes. The root extract at a dose of 5.0 g/kg showed the highest effect. The effect of TCREt was more effective than glibenclamide. Insulin restored all the parameters to near normal levels.

Chronic administration of carbon tetrachloride caused liver fibrosis in rats. Carbon tetrachloride-induced fibrosis was found to significantly elevate the marker enzymes, serum transaminases and alkaline phosphatase as well as lipid peroxidation end product, malondialdehyde or thiobarbituric acid reactive substance in the liver. Fibrosis also caused increase in the serum and tissue cholesterol and decreased tissue phospholipids and free fatty acids. Histopathological examinations also confirm the severe hepatological damage occurred as a consequence of carbon tetrachloride-induced fibrosis. Treatment of curcumin to the fibrotic rats showed a significant improvement after hepatic damage as well as restoration of lipid profile, marker enzymes and thiobarbituric acid reactive substances towards normal.

Syzigium cumini, commonly known as 'jamun', is widely used in Indian folk medicine for the treatment of diabetes mellitus. Oral administration of 2.5 and 5.0 g/kg body weight of the aqueous extract of the seed for 6 weeks resulted in a significant reduction in blood glucose and an increase in total haemoglobin, but in the case of 7.5 g/kg body weight the effect was not significant. It also prevents decrease in body weight. The aqueous extract also resulted in decreased free radical formation in tissues studied. Thus the study shows that Jamun seed extract (JSEt) has hypoglycaemic action. The decrease in thiobarbituric acid reactive substances (TBARS) and increase in reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) clearly show the antioxidant property of the JSEt. The effect of JSEt was most prominently seen in the case of animals given 5.0 g/kg body weight. JSEt was more effective than glibenclamide.

The effect of administration of N-acetylcysteine on ethanol induced hepatotoxicity was studied in female rats and siblings. There was increased activities of serum transaminases and phosphatase in the alcohol fed group. The number of litters born as well as the average birth weight in alcoholic rats were lower. Histopathological alterations were observed in the liver of both mother and litter in the alcohol fed group. The concentration of thiobarbituric acid reactive substances (TBARS) and free fatty acids also increased in the liver. In N-acetylcysteine treated rats, the number of litters as well as the average birth weight were close to that of control animals. The activities of serum transaminases and phosphatase in female rats was higher than the control, but lower than the alcohol fed group. The levels of TBARS and free fatty acids in liver were also decreased both in the mother and litters when compared with alcohol fed animals. Histopathological studies also showed the protective effect of N-acetylcysteine in both mother and litters.

We conducted a double-blind placebo-controlled trial to evaluate the chemopreventive potential of either vitamin A alone or beta carotene alone in subjects with oral leukoplakia in Kerala, India. We randomised 160 fishermen and women with oral precancerous lesions to receive oral vitamin A (retinyl acetate 300,000 IU/week x 12 months, n = 50), or beta carotene (360 mg/week x 12 months, n = 55), or placebo (n = 55). Blood, saliva and urine samples were collected at baseline and at exit to study serum micronutrients and mutagenicity assays. Biopsies of the mucosal lesions at entry were performed for histopathological exclusion of malignancy. The subjects were examined once every 2 months to establish clinical response of lesions and toxicity, if any. The results are based on 43 complaint subjects on placebo, 42 on vitamin A and 46 on beta carotene. The complete regression rates were: 10% in the placebo arm, 52% with vitamin A and 33% with beta carotene (P < 0.0001). Homogeneous leukoplakias and smaller lesions responded better than non-homogeneous and larger lesions. No major toxicities were observed. Half of the responders with beta carotene and two thirds with vitamin A relapsed after stopping supplementation. Serum beta carotene concentration increased substantially with beta carotene administration while with vitamin A supplementation there was no change in serum retinol levels. In the vitamin A treated group there was a significant decrease in serum alpha tocopherol. Vitamin A administration resulted in a significant remission of oral leukoplakia without any side effects of prolonged vitamin A supplementation. The results of this study, as well as those from previous studies, appear to provide strong supporting evidence to justify long term trials with vitamin A in subjects with high-risk leukoplakias with oral cancer as an endpoint.