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Periodontitis is a chronic inflammatory disease which is caused by destruction of the tissues that surrounds and supports the tooth. Deregulation of microRNAs has been reported to cause several inflammatory diseases such as autoimmune disease, chronic periodontitis, and cancer. In the present study, we have investigated the expression pattern of microRNAs let-7a, miR-125b, miR-100, miR-21, and RNA-binding protein LIN-28A among healthy individuals and chronic periodontitis patients. Total RNA was isolated from gingival tissue samples collected from 100 healthy individuals and 100 chronic periodontitis patients. The expression of microRNAs and LIN-28 was performed by qPCR. Target prediction for the microRNAs was done using miRWalk and miRTarbase online databases and the experimentally validated targets were analyzed for their molecular function, biological processes, and related pathways using gProfiler software. The expression analysis revealed that let-7a and miR-21 were upregulated, whereas, miR-100, miR-125b, and LIN-28 were down regulated. The age dependent expression analysis revealed that the expression levels of all the microRNAs and LIN-28 were found to increase with age (more than 50 years), thereby suggesting an increased risk to chronic periodontitis. Among the various targets predicted using miRWalk and miRTarbase databases, NFKB was found to be a common target among all the four microRNAs. gProfiler revealed several functions such as NF-ĸB signaling pathway, cytokine-cytokine receptor interaction, osteoclast differentiation, etc., all of which specific to inflammation and periodontitis.

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.

Periodontitis is an inflammatory disease caused by bacterial triggering of the host immune-inflammatory response, which in turn is regulated by microRNAs (miRNA). Polymorphisms in the miRNA pathways affect the expression of several target genes such as tumor necrosis factor-α and interleukins, which are associated with progression of disease.The objective of this study was to identify the association between the MiR-146a single nucleotide polymorphisms (SNPs) (rs2910164, rs57095329, and rs73318382), the MiR-196a2 (rs11614913) SNP and chronic periodontitis.Genotyping was performed for the MiR-146a (rs2910164, rs57095329, and rs73318382) and the MiR-196a2 (rs11614913) polymorphisms in 180 healthy controls and 190 cases of chronic periodontitis by the direct Sanger sequencing technique. The strength of the association between the polymorphisms and chronic periodontitis was evaluated using logistic regression analysis. Haplotype and linkage analyses among the polymorphisms was performed. Multifactorial dimensionality reduction was performed to determine epistatic interaction among the polymorphisms.The MiR-196a2 polymorphism revealed a significant inverse association with chronic periodontitis. Haplotype analysis of MiR-146a and MiR-196a2 polymorphisms revealed 13 different combinations, of which 5 were found to have an inverse association with chronic periodontitis.The present study has demonstrated a significant inverse association of MiR-196a2 polymorphism with chronic periodontitis.

To address the public health issue of type 2 diabetes (T2D) and its genetic profile in India, we aimed to evaluate genetic determinants of T2D using family-based cohorts from four distinct Endogamous Ethnic Groups (EEGs) representing two Northern (Punjab [Sikhs: SI] and Rajasthan [Agarwals: AG]) and two Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India, and to examine whether genetic variants found through targeted sequencing of the previously established 8 South Asian T2D risk loci (including the one from the Sikh population) are relevant to the AG, CH, and RE EEGs. In this study, we report the findings of T2D occurrence and genetic basis of T2D/related traits from the EEGs, as part of the INDIGENIUS (Indian Diabetes Genetic Studies in collaboration with U.S.) consortium studies, supported by an Indo-U.S. Collaborative Research Partnership on T2D. Data and samples were collected from three EEGs: AG (N=530, Families=25, mean age=43y, mean BMI=27, T2D=37%); CH (N=518, families=21, Age=47y, BMI=27, T2D=33%), and RE (N=500, Families=22, Age=46y, BMI=27, T2D=36%). Each of the families from an EEG was ascertained by a proband with T2D. The status of T2D was defined by ADA 2018 guidelines (fasting glucose≥126 mg/dl or HbA1c≥6.5% and/or use of diabetes medication/history). Similar characteristics for the SI EEG (N=1260, Families=324, Age=51y, BMI=27, T2D=75%) were obtained previously. We used the variance components method as implemented in the program SOLAR to carry out genetic analyses. All analyses were adjusted for age and sex effects. In all cohorts, T2D heritability (h2) (p Disclosure V. Venkatesan: None. J.C. Lopez-Alvarenga: None. R. Arya: None. T. Koshy: None. U. Ravichandran: None. S. Sharma: None. S. Lodha: None. A.R. Ponnala: None. K.K. Sharma: None. M.V. Shaik: None. R.G. Resendez: None. D. Ramu: None. P. Venugopal: None. P. R.: None. N. S.: None. J.A. Ezeilo: None. C.A. Bejar: None. S. Mummidi: None. C. Natesan: None. J. Blangero: None. K.M. Medicherla: None. S. Thanikachalam: None. T. Sadras Panchatcharam: None. D. K.: None. R. Gupta: None. D.K. Sanghera: None. R. Duggirala: None. S.F. Paul: None. Funding Indian Council of Medical Research (55/6/2/Indo-US/2014-NCD-II); National Institute of Diabetes and Digestive and Kidney Diseases (R21DK105913)

Higher education levels are known to be associated with better understanding and awareness of type 2 diabetes (T2D) and its complications. Given the diverse ethnic and socio-cultural characteristics of Indian populations, we aimed to study the effect of educational status on fasting glucose (FG) and HbA1c from three distinct Endogamous Ethnic Groups (EEGs) in India, which are part of the INDIGENIUS consortium, supported by an Indo-U.S. Collaborative Research Partnership on T2D. We obtained data from 1,548 individuals from 68 families (Mean age: 45.5(16)y, 51% men, BMI 26.7(5.2)), representing the communities of Chettiar (34%) from Tamil Nadu state, Agarwal (34%) from Rajasthan state, and Reddy (32%) from Andhra Pradesh state with different levels of income (Low, Middle, High) and education (Uneducated [UE], High School [HS], Graduate [GD], and Postgraduate [PG]). We rank-normalized FG and HbA1c by Van der Waerden's method and performed MANCOVA adjusting for covariates (age, sex, BMI, T2D and income). The main effects were EEG and education level. Data were standardized. Reddys exhibited the lowest value of FG [(-0.05 (SE: 0.06)] compared with Chettiars [0.48 (0.14)] and Agarwals [0.4 (0.04)] p In conclusion, fasting glucose and HbA1c concentrations are influenced by education level independent of income status and population background in the ethnically diverse Indian populations. Disclosure T. Koshy: None. R. Arya: None. J.C. Lopez-Alvarenga: None. V. Venkatesan: None. U. Ravichandran: None. S. Sharma: None. S. Lodha: None. A.R. Ponnala: None. K.K. Sharma: None. M.V. Shaik: None. R.G. Resendez: None. D. Ramu: None. P. Venugopal: None. P. R.: None. N. S.: None. J.A. Ezeilo: None. C.A. Bejar: None. S. Mummidi: None. C. Natesan: None. J. Blangero: None. K.M. Medicherla: None. S. Thanikachalam: None. T. Sadras Panchatcharam: None. D. K.: None. R. Gupta: None. R. Duggirala: None. D.K. Sanghera: None. S.F. Paul: None. Funding Indian Council of Medical Research (55/6/2/Indo-US/2014-NCD-II); National Institute of Diabetes and Digestive and Kidney Diseases (R21DK105913)

Female infertility is often of unknown etiology and is a significant medical problem. It occurs when implantation does not occur; a fertilized embryo fails to survive after implantation; or when the egg cannot move from the ovary to the uterus. The aim of this study was to analyze the role of estrogen receptor 1 (ESR1) genotypes in female infertility.Blood samples were collected from 114 women with infertility undergoing infertility treatment. Samples were also collected from 115 age-matched control women with at least one live child and with no history of infertility or abortions. Genomic DNA was isolated from the blood samples, and genotyping of the ESR1 gene was performed using polymerase chain reaction-restriction fragment length polymorphism.The study revealed the presence of two single nucleotide polymorphisms (SNPs) in the ESR1 gene, PvuII and XbaI. Individual analyses of these two polymorphisms showed that the XbaI heterozygote was significantly increased in controls compared to cases (odds ratio-0.39, confidence interval-0.21 to 0.74, p-0.005). The combined analysis of the PvuII and XbaI genotypes showed no significant difference between the case and control samples.Analysis of the Pvull and Xba1 polymorphisms of the ESR1 gene, demonstrated that the XbaI heterozygote was significantly increased in controls indicating a protective effect.

The present study was aimed to evaluate the protective efficacy of dendrodoine analog (DA), an aminothiazole derivative against the formation of radiation induced dicentric (DC) aberration frequency on cultured human peripheral blood lymphocytes. DA was chemically synthesized and the product thus obtained was purified using column chromatography packed with silica gel using chloroform as the solvent. The purity status of the final product was assessed employing high performance thin layer chromatography (HPTLC). The radioprotective efficacy of DA against the formation of DC aberration frequency was analyzed by pre-incubating human peripheral blood lymphocytes with the optimum concentration of DA, selected from our previous study, followed by exposure to different doses of radiation. The results indicated that there was a dose dependent increase in the formation of DC aberration frequency in the irradiated groups when compared to DA pre-treated groups which modulated the toxic effects of radiation by means of its effective DNA protective and antioxidant property.

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

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.

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.

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 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.

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.

Diabetes and smoking have been considered as major health problems individually and their seriousness related to health hazard has been well reported. The role of nicotine in causing or worsening effect on diabetes is not well understood. The aim of our study was to investigate the effect of nicotine on experimental diabetes and to analyze the effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione a bisdemethoxy curcumin analog (BDMCA) in streptozotocin and nicotine induced toxicity. Group I: control rats; Group II: nicotine (2.5 mg/kg b.wt); Group III: streptozotocin (STZ) (40 mg/kg b.wt); Group IV: STZ (40 mg/kg b.wt) + nicotine (2.5 mg/kg b.wt); Group V: STZ + nicotine + BDMCA (40 mg/kg b.wt); Group VI: STZ + nicotine + BDMCA (80 mg/kg b.wt). Efficacy of BDMCA was determined by evaluating blood glucose, thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP), activities of marker enzymes alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) and activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). From our study, we have observed that nicotine not only aggravates diabetic complications but also increased the risk for diabetes. BDMCA, at a dose 80 mg/kg body weight was found to be more effective in decreasing toxic effects induced by nicotine and STZ.

Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride (CCl₄). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of CCl₄-treated rats. Rats treated with CCl₄ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

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.

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.

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.

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.

The present work was carried out to evaluate the antioxidant and free radical scavenging activity of aminothiazole derivative by performing various in vitro assays; to study its protective effect on H(2)O(2)-induced oxidative damage on pBR322 DNA and on RBC cellular membrane. The in vitro assays were performed with different concentrations of aminothiazole derivative (6.15, 12.29, 18.44, 24.59, and 30.73 microM) and the results were compared with standards like ascorbic acid and trolox. Our results clearly indicated that aminothiazole derivative at a dose of 18.44 microM exhibited radical scavenging activity greater than that of ascorbic acid and trolox. The DNA protective effect on pBR322 DNA showed that there was a concentration-dependent inhibition of the disappearance of supercoiled (ccc) form of DNA on incubation with 30 mM H(2)O(2) in the presence of different concentrations of aminothiazole derivative. Thus our compound at 1.5 mM prevents the conversion from supercoiled (ccc) form to open circular form (oc) form of pBR322 DNA. Pretreatment with aminothiazole derivative at a dose of 18.44 microM prevents membrane damage and exhibits an IC(50) value, which is the concentration of the sample required to inhibit 50% of the radical formed greater than that of the standards (ascorbic acid and trolox). Thus our compound of interest aminothiazole derivative exhibits antioxidant and free radical scavenging properties greater than that of standards like ascorbic acid and trolox and thereby protects pBR322 DNA and RBC cellular membrane from free radical induced oxidative damage.

Bromelain (Br), a proteolytic enzyme extracted from the stem of the pineapple, is known to possess anti-inflammatory activity and has been shown to reduce blood viscosity, prevent the aggregation of blood platelets, and improve ischemia-reperfusion (I/R) injury in a skeletal muscle model. We investigated the capacity of Br to limit myocardial injury in a global I/R model. Adult male Sprague-Dawley rats were divided into two groups: control (PBS) and Br at 10 mg/kg in PBS administered via intraperitoneal injection (twice/day) for 15 consecutive days. On day 16, the hearts were excised and subjected to 30 min of global ischemia followed by 2 h of reperfusion. Br treatment showed higher left ventricular functional recovery throughout reperfusion compared with the controls [maximum rate of rise in intraventricular pressure (dP/d tmax), 2,225 vs. 1,578 mmHg/s at 2 h reperfusion]. Aortic flow was also found to be increased in Br treatment when compared with that in untreated rats (11 vs. 1 ml). Furthermore, Br treatment reduced both the infarct size (34% vs. 43%) and the degree of apoptosis (28% vs. 37%) compared with the control animals. Western blot analysis showed an increased phosphorylation of both Akt and FOXO3A in the treatment group compared with the control. These results demonstrated for the first time that Br triggers an Akt-dependent survival pathway in the heart, revealing a novel mechanism of cardioprotective action and a potential therapeutic target against I/R injury.

This study addresses an important clinical issue by identifying potential candidates of vascular endothelial growth factor (VEGF) signalling through the Flk-1 receptor that trigger cardioprotective signals under ischaemic stress. Isolated working mouse hearts of both wild-type (WT) and Flk-1(+/-) were subjected to global ischaemia (I) for 30 min. followed by 2 hrs of reperfusion (R). Flk-1(+/-) myocardium displayed almost 50% reduction in Flk-1 mRNA as examined by quantitative real-time RT-PCR at the baseline level. Flk-1(+/-) mouse hearts displayed reduction in left ventricular functional recovery throughout reperfusion (dp/dt 605 versus 884), after 2 hrs (P0.05). Coronary (1.9 versus 2.4 ml) and aortic flow (AF) (0.16 versus 1.2 ml) were reduced in Flk-1(+/-) after 2 hrs of reperfusion. In addition, increased infarct size (38.4%versus 28.41%, P0.05) and apoptotic cardiomyocytes (495 versus 213) were observed in Flk-1(+/-) knockout (KO) mice. We also examined whether ischaemic preconditioning (PC), a novel method to induce cardioprotection against ischaemia reperfusion injury, through stimulating the VEGF signalling pathway might function in Flk-1(+/-) mice. We found that knocking down Flk-1 resulted in significant reduction in the cardioprotective effect by PC compared to WT. Affymetrix gene chip analysis demonstrated down-regulation of important genes after IR and preconditioning followed by ischaemia reperfusion in Flk-1(+/-) mice compared to WT. To get insight into the underlying molecular pathways involved in ischaemic PC, we determined the distinct and overlapping biological processes using Ingenuity pathway analysis tool. Independent evidence at the mRNA level supporting the Affymetrix results were validated using real-time RT-PCR for selected down-regulated genes, which are thought to play important roles in cardioprotection after ischaemic insult. In summary, our data indicated for the first time that ischaemic PC modifies genomic responses in heterozygous VEGFR-2/Flk-1 KO mice and abolishes its cardioprotective effect on ischaemic myocardium.

The goal of primary chemoprevention is to decrease the incidence of a given cancer, simultaneously reducing treatment-related adverse events, cost of treatment of the disease and mortality. Prostate cancer is an attractive and appropriate target for primary prevention because of its high incidence and prevalence, increased disease-related mortality, long latency and molecular pathogenesis and epidemiological data indicating that modifiable environmental factors may decrease risk. Various agents have been suggested to prevent prostate cancer and many clinical trials are currently on. Ultimately the adoption of a preventive strategy hinges on its potential benefits weighed against the potential risks of the specific agents used. This article is aimed to examine the experimental and epidemiological data spanning a period of 1998 to 2007, demonstrating the chemopreventive activity, safety and toxicity of various nutritional elements and other agents that can help prevent prostate cancer and/or slow disease progression.

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.

Nicotine, the principal alkaloid in tobacco, is generally considered to be an active pharmacological agent responsible for lung-related disorders. The actions of nicotine have been extensively investigated in animal and variety of cell systems. Nicotine is known to induce the lipid peroxidation by producing reactive oxygen species and reactive nitrogen species. In the present study, we have investigated the effect of hesperidin on nicotine toxicity. The parameters studied were marker enzymes and antioxidant status in blood, tissues, BAL (bronchoalveolar lavage cells) and BALF (bronchoalveolar lavage fluid). Lung damage was induced by subcutaneous injection of nicotine at a dosage of 2.5 mg/kg body weight for 5 days a week. Hesperidin was administered orally at a dose of 25 mg/kg body weight. The results showed an increase in the level of marker enzymes and decrease in the antioxidant status in nicotine-treated rats. Hesperidin treatment resulted in a decreased level of all the marker enzymes and the antioxidant status was brought back to near normal. Thus the study shows that hesperidin offers protection against the lung damage caused by nicotine.

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.

The protective effect of dendrodoine analog (DA) [4-amino-5-benzoyl-2-(4-methoxy phenylamino) thiazole] at three doses (5, 10, and 15 mg/kg body weight) was investigated on ethanol-induced hyperlipidemia. Hepatotoxicity was induced by administering 7.9 g ethanol/kg body weight for 45 days by intragastric intubation. Our results showed increased activity of aspartate transaminase (AST), alkaline phosphatase (ALP), and gamma glutamyl transferase (GGT) and increased levels of cholesterol, triglycerides, and phospholipids in the plasma of alcohol-given group when compared with normal control group. The levels of tissue (liver and kidney) cholesterol and triglycerides were increased significantly in alcohol control rats when compared with normal control rats. The levels of phospholipids decreased significantly in the liver and kidney of alcohol control rats when compared with normal control rats. The activity of phospholipase A and phospholipase C increased significantly in the liver of alcohol control rats when compared with normal control rats. Intragastric administration of DA at 10 mg/kg body weight effectively lowered the activity of hepatic marker enzymes (GGT, AST, and ALP), phospholipase A, and phospholipase C, and decreased the levels of plasma and tissue lipids. The level of tissue phospholipids increased significantly when DA was administered at a dose of 10 mg/kg body weight along with alcohol when compared with alcohol control group. Thus, we propose that DA exerts a hepatoprotective effect by modulating liver marker enzymes and lipid levels at a dosage of 10 mg/kg body weight.

There has been considerable public and scientific interest in the use of phytochemicals derived from dietary components to combat human diseases. They are naturally occurring substances found in plants. Ferulic acid (FA) is a phytochemical commonly found in fruits and vegetables such as tomatoes, sweet corn and rice bran. It arises from metabolism of phenylalanine and tyrosine by Shikimate pathway in plants. It exhibits a wide range of therapeutic effects against various diseases like cancer, diabetes, cardiovascular and neurodegenerative. A wide spectrum of beneficial activity for human health has been advocated for this phenolic compound, at least in part, because of its strong antioxidant activity. FA, a phenolic compound is a strong membrane antioxidant and known to positively affect human health. FA is an effective scavenger of free radicals and it has been approved in certain countries as food additive to prevent lipid peroxidation. It effectively scavenges superoxide anion radical and inhibits the lipid peroxidation. It possesses antioxidant property by virtue of its phenolic hydroxyl group in its structure. The hydroxy and phenoxy groups of FA donate electrons to quench the free radicals. The phenolic radical in turn forms a quinone methide intermediate, which is excreted via the bile. The past few decades have been devoted to intense research on antioxidant property of FA. So, the present review deals with the mechanism of antioxidant property of FA and its possible role in therapeutic usage against various diseases.

Alcoholic fibrosis and its end-stage cirrhosis occur when the rate of matrix synthesis exceeds matrix degradation. Hepatic fibroproliferation is associated with alterations of hepatic tissue inhibitors of matrix metalloproteinase (TIMPs) and matrix metalloproteinases (MMPs/matrixins) expressions. The alteration of hepatic matrixins and TIMPs expression to disease stage and inflammatory activity underlines their potential diagnostic markers in chronic liver disease. Ellagic acid (EA), a natural phenolic compound found in fruits and nuts, has potent antioxidant, anti-inflammatory, and anticancerous properties. The aim of our study was to gain further insight into the effect of EA on fibrotic markers (MMPs and TIMPs) during alcohol-induced tissue injury. To elucidate the effect on the MMPs/TIMPs balance by EA, gelatin zymography, multiwell zymography, succinylated gelatin assay, and ELISA technique (for TIMPs) were carried out. Coadministration of EA with alcohol decreased the expression of MMP-2 and -9 and TIMP-2 in a dose-dependent manner. These results suggest that EA at the dosage of 60 mg/kg body weight effectively decreased the expression pattern of fibrotic markers during alcohol-induced toxicity. Hence, it can be developed as an antifibrotic compound in near future.

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.

Alcohol is a neurotoxin associated with significant mortality and morbidity. Ethanol is found to induce a dose-dependent increase in lipid peroxidation. The elevation in lipid peroxidative products and the loss of antioxidant defense potential are enhanced when alcohol is consumed along with polyunsaturated fatty acids. The present study evaluated the effect of Cuminum cyminum on lipid peroxidation induced by ethanol and preheated (to oxidize) sunflower oil. Hepatotoxicity, assessed by the activities of plasma aspartate transaminase (AST), alkaline phosphatase (ALP), and γ-glutamyl transferase (GGT), was apparent in rats fed alcohol and preheated oil as compared with control rats on a normal diet. The toxicity was associated with lipid peroxidation and a disruption in the antioxidant defense mechanism, as evidenced by increased levels of thiobarbituric acid reactive substances (TBARS), hydroperoxides, and free fatty acids (FFA) in the liver; decreased levels of glutathione, vitamin C, and vitamin...

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.

We have evaluated the comparative effect of curcumin (diferuloyl methane) and its analogue [bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione] (BDMC-A) on carbon tetrachloride-induced hepatotoxicity in rats. Administration of carbon tetrachloride (3 ml/kg/week) for three months significantly (P

Nicotine, a major toxic component of cigarette smoke, plays a key role in the development of cardiovascular disease and lung cancer. In the present study, we have synthesized an analog of curcumin and biomonitored its influence over biochemical marker enzymes and lipid profiles on nicotine-induced toxicity in Wistar rats. The effects were compared with that of curcumin, a well-known antioxidant and anti-hyperlipidemic agent. Toxicity was induced by subcutaneous injection of nicotine at a dose of 2.5 mg/kg of body weight (5 days a week, for 22 weeks), and curcumin (80 mg/kg) was given simultaneously along with nicotine by intragastric intubation for 22 weeks. Measurements of activities of the biochemical marker enzymes aspartate transaminase, alanine transaminase, alkaline phosphatase, and lactate dehydrogenase and of plasma lipid profiles were used to monitor the anti-hyperlipidemic effects of curcuminoids. In nicotine-treated rats, enhanced plasma marker enzymes and lipid profiles were observed. Administration of curcumin or curcumin analog to nicotine-treated rats significantly reduced the activity of marker enzymes and plasma lipid levels. Thus, our findings suggest that curcumin and its analog exert an anti-hyperlipidemic effect against nicotine-induced lung toxicity and may be a promising agent for treatment of hyperlipidemia and atherosclerosis.

Ethanol is a powerful inducer of hyperlipidemia in both animals and humans. Lipid abnormalities seen after ethanol consumption include alterations in the levels of free cholesterol, cholesteryl esters, fatty acids, phospholipids and triacylglycerol. Intake of high fat diet along with ethanol primes the hyperlipidemic effects of ethanol. Alcohol induced disturbances in lipid pattern were found to be exacerbated when the fat is thermally oxidized. In the present communication, we have investigated the influence of ferulic acid, a naturally occurring nutritional component on alcohol and thermally oxidized sunflower oil (?PUFA) induced hyperlipidemia. To evaluate the antihyperlipidemic potential of ferulic acid (FA), we analyzed the variation in lipid profiles cholesterol, triglycerides (TG), phospholipids (PL) and free fatty acids (FFA) in plasma, liver, heart and kidney. The results showed that there was a significant elevation in the levels of cholesterol, TG and FFA in alcohol, ?PUFA, alcohol + ?...

Alcohol use is contributing to an unprecedented decline in life expectancy. It induces hyperlipidemia when taken at higher concentrations. Alcoholics usually after a heavy binge of alcohols take fried food items normally made up of polyunsaturated fatty acids (PUFAs). The combined ingestion of alcohol and PUFAs is considered to be dangerous and known to result in hyperlipidemic conditions. Previous studies have shown that curcumin, an active principle of turmeric (Curcuma longa), has antihyperlipidemic properties. So in the present work we have synthesized an analog of curcumin and tested the protective role of that synthetic curcuminoid on alcohol and thermally oxidized sunflower oil-induced hyperlipidemia. Male Albino rats of Wistar strain were used for the experimental study. Antihyperlipidemic activity of the synthetic curcuminoid was evaluated by analyzing the levels of lipids (cholesterol, triglycerides [TGs], phospholipids [PLs], and free fatty acids [FFAs]) in different tissues and histopathological changes in the liver. The results showed that the levels of cholesterol, TGs, and FFAs were increased significantly in alcohol, thermally oxidized sunflower oil (Delta PUFA), and alcohol + Delta PUFAs treated groups. Administration of synthetic curcuminoid effectively reduced these levels. The phospholipid (PL) levels, which were decreased in the liver and kidney and increased in the heart in the alcohol, Delta PUFA, and alcohol + Delta PUFA groups, were positively modulated by treatment with synthetic curcuminoid (CA). Our histopathological observations were also in correlation with the biochemical parameters. From the results obtained, we could conclude that the synthetic curcuminoid effectively protects the system against alcohol and Delta PUFA-induced hyperlipidemia and may become an effective therapeutic agent for the treatment of hyperlipidemia.

Curcumin and its analogue (bis.demethoxy curcumin analogue [BDMC-A]) were studied for their possible lipid-lowering properties in carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Carbon tetrachloride (3 ml kg−1 wk−1) administration to albino Wistar rats increased the levels of hepatic marker enzymes such as aspartate transaminase (AST), alkaline phosphatase (ALP), and γ.-glutamyl transferase (GGT) in the plasma. The levels of lipids cholesterol, triglycerides, and free fatty acids were also increased in plasma and tissues (liver, kidney, heart, and brain). Phospholipid levels increased in plasma, heart, and brain but decreased in liver and kidney. Curcumin (80 mg/kg) and BDMC-A (80 mg/kg) administration to CCl4-treated rats for a period of 3 months significantly decreased the lipid levels. The effect exerted by BDMC-A was more prominent than that of curcumin. Studies on the histopathology of the liver are also in line with the biochemical parameters studied. These observations show the ...

Aim: The current study was undertaken to assess the effect of ethanol and thermally oxidized sunflower oil ingestion on liver phospholipid fatty acids and the protective role of Cuminum cyminum L. Methods: Ethanol was administered at a level of 20% and thermally oxidized sunflower oil at a level of 15% for 45 days. C. cyminum was administered at a dosage of 250 mg/kg body weight for 45 days. We investigated the changes in the liver phospholipid fatty acid composition. Results: Ethanol and thermally oxidized sunflower oil administration modifies the fatty acid composition and the analysis of fatty acids showed that there was a significant increase in the concentrations of 16:0, 16:1, 18:0, 18:1 and 18:2, whereas the concentration of 20:4 was significantly decreased. The concentrations of 16:0, 16:1, 18:0, 18:1 and 20:4 were near normal in cumin-treated rats. Conclusion: The present investigation shows that cumin prevents the changes in the composition of fatty acids, which were produced by ethanol and thermally oxidized oil.

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.