Effect of 4 % chlorhexidine on cord colonization among hospital and community births in India: a randomized controlled study.

BACKGROUND: Infections are the single most important cause of neonatal mortality in developing countries. Results from trials in Asia evaluating the effect of chlorhexidine on neonatal mortality have been encouraging but limited data are available on the impact of cord cleansing on bacterial colonization. Further, no data from facility deliveries and impact with time is available. This pilot study was aimed to evaluate the impact of 4 % commercially prepared chlorhexidine on cord colonization and density of colonization among newborns in India. METHODS: Three hundred twenty-six newborns (hospital-247; community-79) were enrolled within 24 h of birth and randomly assigned to one of three groups: chlorhexidine, placebo or dry cord care. Umbilical swabs were collected at baseline, 2- and 48- hours after intervention application. RESULTS: At baseline, growth positivity (any bacterial growth) was 20 % (50 of 247 swabs) and 81 % (64 of 79 swabs) among hospital and community born neonates, respectively. In both settings, chlorhexidine compared to placebo and dry cord care, reduced colonization following 2- and 48-hour post application. Chlorhexidine significantly reduced 48-hour post application colony counts in comparison to placebo [Hospital: mean difference = -1.01; 95 % CI: -1.72, -0.30 Community: mean difference = -1.76; 95 % CI: -2.60, -0.93] and dry cord care [Hospital: mean difference = -1.16; 95 % CI: -1.93, -0.39 Community: mean difference = -2.23; 95 % CI: -3.18, -1.29]. Differences were similar for gram-positive and gram-negative bacteria. CONCLUSIONS: Cord cleansing with 4 % chlorhexidine soon after birth reduced colonization as well as density of colonization significantly; however this pilot study does not address the impact of chlorhexidine on mortality. The control preparation neither increased or decreased colonization. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov: NCT01528852, Registered February 7, 2012.

Efficiency of red cell distribution width in identification of children aged 1-3 years with iron deficiency anemia against traditional hematological markers.

BACKGROUND: Current strategy to identify iron deficiency anemia relies on markers involving high costs. Reports have suggested red cell distribution width (RDW) as a potential screening test for identifying iron deficiency anemia (IDA) but studies in pediatric populations are lacking. Our study elucidates the discriminative ability of RDW for detecting IDA among young children. METHODS: 2091 blood reports of children aged 1-3 years from an urban low socio-economic population of Delhi were analyzed to evaluate the sensitivity of RDW in discriminating IDA using receiver's operating characteristic curve. Hemoglobin and RDW were estimated using coulter, zinc protoporphyrin with AVIV fluorometer and serum ferritin by enzyme linked immunosorbent assay. RESULTS: A total of 1026 samples were classified as iron deficient anemia using gold standard. As a marker of overall efficiency, area under the curve for RDW was 0.83 (95% CI, 0.81- 0.84; p < 0.001). Sensitivity of RDW at cut-off of 18% to detect iron deficiency anemia was 76.5% and specificity 73.1% yielding a positive predictive value of 73% and negative predictive value of 76%. At a cut-off of RDW 16.4%, the sensitivity was 94% and at a cut-off of 21%, the specificity was 95%. Combination of hemoglobin ≤ 10 g/dL and RDW >15%, yielded a sensitivity of 99% and specificity of 90%. These data suggest that simple coulter analysis estimating hemoglobin and RDW can be used for identification of children in need for iron therapy. CONCLUSIONS: In India and similar settings, RDW >15% with hemoglobin ≤ 10.0 g/dL identifies iron deficient anemic children without need for iron status markers which could help reduce cost of management especially in poor settings. TRIAL REGISTRATION: Clinicaltrials.gov NCT00255385.

Compliance with home-based fortification strategies for delivery of iron and zinc: its effect on haematological and growth markers among 6-24 months old children in north India.

Compliance is a key component in successful implementation of the delivery of micronutrients among children. The present study evaluates the compliance with two home-based food fortification strategies (fortified complementary food or sprinkle) for providing iron and zinc among children aged 6-24 months. A total of 292 children were randomly allocated to receive either rice-based fortified complementary food and nutrition education (Cf = 101), sprinkle and nutrition education (Mp = 97), or nutrition education alone as control (Ed = 94). All the enrolled children were breastfed at the beginning of the study and were advised to continue breastfeeding. Biweekly information on compliance and anthropometry was collected. Complete haemogram estimation was conducted at baseline and end of the study. Compliance with the fortified complementary food was higher compared to sprinkle (Cf = 81%, Mp = 64% child-days). Consumption of the fortified complementary food for 6 months resulted in a significant increase in mean haemoglobin in the intervention group compared to control group (Cf 1.29 +/- 1.6 g/dL; Ed 0.23 +/- 1.3 g/dL; p < 0.001). Our results showed that fortified complementary food had higher compliance than sprinkle and is a suitable delivery mechanism for iron and zinc in preschool children.

Anti-inflammatory role of naringenin in rats with ethanol induced liver injury.

The aim of the study was to investigate the antiinflammatory effects of naringenin in rats induced liver damage by exposure to ethanol. Rats were divided into four groups, groups 1 and 2 received isocaloric glucose; groups 3 and 4 received 20% ethanol equivalent to 6 g/kg body weight everyday for the total experimental period of 60 days. In addition, groups 2 and 4 were supplemented with naringenin (50 mg/kg p.o.) everyday for the last 30 days of the experiment. The results showed significantly elevated levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, transforming growth factor-alpha (TNF-α), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB), cyclooxygenase-2 (COX-2), macrophage inflammatory protein 2 (MIP-2) and CD14 in ethanol fed rats as compared to those of the control. Ethanol-fed rats exhibited increased staining for the presence of inducible nitric oxide (iNOS) protein adducts in the liver. Supplementation with naringenin for the last 30 days to ethanol-fed rats, significantly decreased the levels/activities/expression of serum aspartate and alanine transaminases, iron, ferritin, TNF-α, IL-6, NF-κB, COX-2, MIP-2, CD14 and iNOS protein adducts in the liver as compared to the untreated ethanol fed rats. The inhibition of TNF-α, IL-6, NF-κB, COX-2, MIP-2, iNOS and CD14 by naringenin may contribute to its antiinflammatory activity in ethanol fed rats.

Comparative and combined effect of chlorogenic acid and tetrahydrocurcumin on antioxidant disparities in chemical induced experimental diabetes.

The present study evaluates the combined effect of tetrahydrocurcumin and chlorogenic acid on oxidative stress in streptozotocin-nicotinamide-induced diabetic rats. Rats were rendered diabetic by a single intraperitoneal injection (i.p) of streptozotocin (45 mg/kg BW), 15 min after an i.p injection of nicotinamide (110 mg/kg BW). The levels of fasting plasma glucose and insulin were estimated. As an index of oxidative stress, the levels of enzymic antioxidants and lipid peroxidation products were analyzed in liver and kidney. Diabetic rats showed an increase in the levels of fasting plasma glucose, lipid peroxidative products such as thiobarbituric acid reactive substances and lipid hydroperoxides and a decrease in plasma insulin, and enzymic antioxidants viz., superoxide dismutase, catalase, glutathione peroxidase and glutathione-S-transferase. Combined administration of tetrahydrocurcumin (80 mg/kg BW) and chlorogenic acid (5 mg/kg BW) to diabetic rats for 45 days, reversed the biochemical changes to near normal. The above findings were supported by histological observations of the liver and kidney. Together the present study clearly reflects that combined dosage of tetrahydrocurcumin and chlorogenic acid augments enzymic antioxidants with a concomitant decrease in lipid peroxidation and protects against streptozotocin-nicotinamide-induced type 2 diabetes in experimental rats.

Effects of Bifidobacterium lactis HN019 and prebiotic oligosaccharide added to milk on iron status, anemia, and growth among children 1 to 4 years old.

OBJECTIVE: To evaluate the effect of Bifidobacterium lactis HN019 and prebiotic-fortified milk on iron status, anemia, and growth among 1- to 4-year-old children. PATIENTS AND METHODS: In a community-based double-masked, controlled trial in a periurban population, 624 children were enrolled and randomly allocated to receive either milk fortified with additional probiotic and prebiotic (n = 312) or control milk (n = 312) for 1 year. Probiotic and prebiotic milk contained an additional 1.9 x 10 colony-forming units per day of probiotic B lactis HN019 and 2.4 g/day of prebiotic oligosaccharides milk. Hematological parameters were estimated at baseline and at the end of the study. Height and weight measurements were recorded at baseline, mid study, and the end of the study. Difference of means and multivariate regression models was used to examine the effect of intervention. RESULTS: Both study groups were similar at baseline. Compliance was high (>85%) and did not vary by intervention groups. As compared with non-fortified milk, consumption of probiotic- and prebiotic-fortified milk for a period of 1 year reduced the risk of being anemic and iron deficient by 45% (95% CI 11%, 66%; P = 0.01) and increased weight gain by 0.13 kg/year (95% CI 0.03, 0.23; P = 0.02). CONCLUSIONS: Preschoolers are usually fed milk, which has good acceptance and can be easily fortified for delivery of probiotics. Consumption of B lactis HN019 and prebiotic-fortified milk resulted in a smaller number of iron-deficient preschoolers and increased weight gain.

Combined treatment of tetrahydrocurcumin and chlorogenic acid exerts potential antihyperglycemic effect on streptozotocin-nicotinamide-induced diabetic rats.

We have shown that separate dose of tetrahydrocurcumin (THC) at a dose of 80 mg/kg body weight (b.w.) and chlorogenic acid (CGA) at a dose of 5 mg/kg b.w. exerts antidiabetic potential in streptozotocin (STZ) (45 mg/kg b.w.) nicotinamide induced diabetic rats. In the present study we have attempted to compare the antihyperglycemic activity exerted by the combined treatment of THC/CGA with THC and CGA alone treated diabetic rats. After the experimental period of 45 days we observed that supplementation with combined dose of THC/CGA significantly decreased glycosylated hemoglobin (HbA(1C)) and increased the levels of plasma insulin, C-peptide, hemoglobin and glycogen which were decreased upon STZ treatment and also significantly reversed the altered activities of gluconeogenic enzymes such as glucose-6-phosphatase, fructose-1,6-bisphosphatase, and of glycolytic enzymes such as glucokinase and hexokinase in the tissues of experimental rats as compared to their individual supplementation. Thus our results substantiate that though THC and CGA alone found to exert hypoglycemic activity the maximum hypoglycemic effect was always observed in diabetic rats treated THC/CGA and this summed effect seems to have a promising value for the development of a potent phytomedicine for diabetes.

Hepatoprotective role of bis-demethoxy curcumin analog on the expression of matrix metalloproteinase induced by alcohol and polyunsaturated fatty acid in rats.

Liver fibrosis is one of the major health problems worldwide. Chronic alcohol abuse is one of the main causes of fibrosis. Ingestion of polyunsaturated fatty acids (PUFA) along with alcohol further aggravates the toxicity of alcohol. Fibrosis results due to increased deposition of extra cellular matrix (ECM). The degree of abnormal ECM degradation depends on the ratio of active matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The present work studied the influence of bis-desmethoxy curcumin analog (BDMC-A) on the expression of MMPs and TIMPs during alcohol and DeltaPUFA induced liver toxicity. Male albino Wistar rats were used for the study. The MMP expression was found to be increased in alcohol as well as DeltaPUFA treated rats and decreased in alcohol + DeltaPUFA treated rats. The levels of TIMPs and the collagen were increased in alcohol, DeltaPUFA, and alcohol + DeltaPUFA groups. Administration of BDMC-A significantly decreased the levels of collagen and TIMPs; and positively modulated the expression of MMPs. From this study, it is concluded that BDMC-A influences MMPs, TIMPs expression, and acts as an efficient anti-fibrotic agent.

Evaluation of antioxidant activity of hesperidin and its protective effect on H2O2 induced oxidative damage on pBR322 DNA and RBC cellular membrane.

The present work was carried out to evaluate the antioxidant activity of hesperidin and to study its protective effect on H(2)O(2) induced oxidative damage on pBR322 DNA and RBC cellular membrane. The in vitro assays were performed with different concentrations (2, 4, 6, 8, and 10 microg/ml, which were equivalent to 3.27, 6.55, 9.83, 13.10, and 16.38 microM) of hesperidin and the results clearly indicate that hesperidin at 10 microg/ml exhibited radical scavenging activity greater than that of standards like ascorbic acid and trolox. The protective effect of hesperidin on pBR322 DNA and RBC cellular membrane on treatment with different concentrations of H(2)O(2) shows that hesperidin at 2.5 mM converts the open circular form (oc) of pBR322 DNA that is an indication of damage to super coiled (ccc) form and at 10 microg/ml it prevents membrane damage. Thus, our result proves hesperidin to be a valuable antioxidant that protects pBR322 DNA and RBC cellular membrane from free radical induced oxidative damage.

Investigation of the radioprotective efficacy of hesperidin against gamma-radiation induced cellular damage in cultured human peripheral blood lymphocytes.

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.

Zinc deficiency: descriptive epidemiology and morbidity among preschool children in peri-urban population in Delhi, India.

Community-based data relating to factors influencing zinc deficiency among preschool children in India are inadequate. Data of a large, double-blinded, randomized, controlled zinc-supplementation trial were used for assessing the descriptive epidemiology of zinc deficiency among children aged 6-35 months (n = 940). In total, 609 children were followed up for 120 days for information on morbidity. Of these children, 116 from the control group belonging to the upper and the lower 25th quartile of plasma zinc status at baseline were selected for assessing the association of zinc deficiency with prospective morbidity. At baseline, demographic, socioeconomic and dietary information was collected, and anthropometric measurements and levels of plasma zinc were assessed. At baseline, 73.3% of the children were zinc-deficient (plasma zinc < 70 microg/dL), of which 33.8% had levels of plasma zinc below 60 microg/dL. A significantly higher risk of morbidity was prevalent among the subjects with lower plasma zinc compared to those with higher levels of plasma zinc.

Protective effect of Withaferin-A on tumour formation in 7,12-dimethylbenz[a]anthracene induced oral carcinogenesis in hamsters.

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.

Influence of ferulic acid on nicotine-induced lipid peroxidation, DNA damage and inflammation in experimental rats as compared to N-acetylcysteine.

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.

Protective effect of quercetin on nicotine-induced prooxidant and antioxidant imbalance and DNA damage in Wistar rats.

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 2.5mg/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.

Effect of curcumin analog on gamma-radiation-induced cellular changes in primary culture of isolated rat hepatocytes in vitro.

The present study was aimed to evaluate the radioprotective effect of curcumin analog, on gamma-radiation-induced toxicity in primary cultures of isolated rat hepatocytes. Hepatocytes were isolated from the liver of rats by collagenase perfusion. The DNA damage was analysed by single cell gel electrophoresis (comet assay). An increase in the severity of DNA damage was observed with the increase in gamma-radiation dose at 1-4 Gy in cultured rat hepatocytes. The levels of lipid peroxidative indices like thiobarbituric acid reactive substances (TBARSs) were increased significantly, whereas the levels of reduced glutathione (GSH) and antioxidant enzymes were significantly decreased in gamma-irradiated groups. The maximum damage to hepatocytes was observed at 4Gy gamma-irradiation. Pretreatment with different concentrations of curcumin analog (1.38, 6.91 and 13.82 microM) shows a significant decrease in the levels of TBARS and DNA damage. Pretreatment with curcumin analog prevents the loss of enzymic and non-enzymic antioxidants like GSH upon gamma-irradiation. The maximum protection of hepatocytes was observed at 6.91 microM of curcumin analog pretreatment. Thus, our result shows that pretreatment with curcumin analog protects the hepatocytes against gamma-radiation-induced cellular damage.

Caffeic acid protects human peripheral blood lymphocytes against gamma radiation-induced cellular damage.

In the present study, we investigated in vitro radioprotective potential of caffeic acid (CA), a naturally occurring catecholic acid against gamma radiation-induced cellular changes. Different concentrations of CA (5.5, 11, 22, 44, 66, and 88 microM) were incubated with lymphocytes for 30 min prior to gamma-irradiation, and micronuclei (MN) scoring and comet assay were performed to fix the effective concentration of CA against gamma-irradiation. Among all concentrations, 66 microM of CA showed the optimum protection by effectively decreasing the MN frequencies and comet attributes. From the above-mentioned results, 66 microM of CA was selected as the effective concentration and was further used to investigate its radioprotective efficacy. For that purpose, a separate experiment was carried out on the lymphocytes in which lymphocytes were preincubated with CA (66 microM) and were 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. Gamma-irradiated lymphocytes showed a dose-dependent increase in the genetic damage and thiobarbituric acid reactive substances, accompanied by the significant decrease in the antioxidant status, whereas CA pretreatment positively modulated all the radiation-induced changes through its antioxidant potential. The current study demonstrates that CA is effective in protecting lymphocytes against radiation-induced toxicity and encourages further in vivo study to evaluate radioprotective efficacy of CA.

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.

Quercetin ameliorates gamma radiation-induced DNA damage and biochemical changes in human peripheral blood 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.

Antigenotoxic Effects of Curcumin and Piperine Alone or in Combination Against 7,12-Dimethylbenz(a)anthracene Induced Genotoxicity in Bone Marrow of Golden Syrian Hamsters.

ABSTRACT The present study investigates the effect of curcumin and piperine alone or in combination against 7,12-dimethylbenz[a]anthracene (DMBA)-induced genotoxicity in the bone marrow of hamsters. The antigenotoxic effect was evaluated by analyzing the frequency of micronucleated polychromatic erythrocytes (MnPCEs) and chromosomal aberrations. Genotoxicity was induced in experimental hamsters by single intraperitoneal injection of DMBA (30 mg/kg b.w). Oral pretreatment of curcumin (80 mg/kg b.w), piperine (50 mg/kg b.w), and curcumin (80 mg/kg b.w) + piperine (50 mg/kg b.w), respectively, for 5 days, significantly reduced the frequency of MnPCEs and the percentage of chromosomal aberrations in the bone marrow of hamsters. The results suggest that cucumin and piperine in combination have a potent antigenotoxic effect as compared to either agent alone in DMBA-induced genotoxicity in golden Syrian hamsters.

VEGFR1 (Flt-1+/-) gene knockout leads to the disruption of VEGF-mediated signaling through the nitric oxide/heme oxygenase pathway in ischemic preconditioned myocardium.

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.