Showing papers by "University of Madras published in 2012"

Menarche, menopause, and breast cancer risk: Individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies

Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.

Anti‐Inflammatory Property of n‐Hexadecanoic Acid: Structural Evidence and Kinetic Assessment

Abstract: Ester bond hydrolysis of membrane phospholipids by Phospholipase A2 and consequent release of fatty acids are the initiating steps of inflammation It is proposed in this study that the inhibition of phospholipase A2 is one of the ways to control inflammation Investigations are carried out to identify the mode of inhibition of phospholipase A2 by the n-hexadecanoic acid It may help in designing of specific inhibitors of phospholipase A2 as anti-inflammatory agents The enzyme kinetics study proved that n-hexadecanoic acid inhibits phospholipase A2 in a competitive manner It was identified from the crystal structure at 25 A resolution that the position of n-hexadecanoic acid is in the active site of the phospholipase A2 The binding constant and binding energy have also been calculated using Isothermal Titration Calorimetry Also, the binding energy of n-hexadecanoic acid to phospholipase A2 was calculated by in silico method and compared with known inhibitors It may be concluded from the structural and kinetics studies that the fatty acid, n-hexadecanoic acid, is an inhibitor of phospholipase A2, hence, an anti-inflammatory compound The inferences from the present study validate the rigorous use of medicated oils rich in n-hexadecanoic acid for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda

Synthesis and characterization of chitosan-silver nanocomposite

Abstract: Chitosan–silver (CS–Ag) nanocomposite materials were synthesized by a simple chemical method. The synthesized CS–Ag nanocomposite contains 20 wt% silver. Silver nanoparticles were synthesized by chemical reduction method as well. The CS–Ag nanocomposite was characterized using Field emission scanning electronic microscope (FESEM), X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The XRD pattern indicated the presence of both silver and chitosan in the nanocomposite. It is observed from the XRD pattern of silver that it is of cubic structure. The spherical morphology of silver nanoparticles was confirmed from the FESEM image. FTIR spectroscopy was used for the structural elucidation. CS–Ag nanocomposite exhibits good antimicrobial and antitumor properties.

Potential preventive effect of carvacrol against diethylnitrosamine-induced hepatocellular carcinoma in rats.

Abstract: Antioxidants are one of the key players in tumorigenesis, several natural and synthetic antioxidants were shown to have anticancer effects. The aim of the present study is to divulge the chemopreventive nature of carvacrol during diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats. Administration of DEN to rats resulted in increased relative liver weight and serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl transpeptidase (γGT). The levels of lipid peroxides elevated (in both serum and tissue) with subsequent decrease in the final body weight and tissue antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol supplementation (15 mg/kg body weight) significantly attenuated these alterations, thereby showing potent anticancer effect in liver cancer. Histological observations and transmission electron microscopy studies were also carried out, which added supports to the chemopreventive action of the carvacrol against DEN-induction during liver cancer progression. These findings suggest that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the antioxidant system in DEN-induced hepatocellular carcinogenesis.

A series of oxyimine-based macrocyclic dinuclear zinc(II) complexes enhances phosphate ester hydrolysis, DNA binding, DNA hydrolysis, and lactate dehydrogenase inhibition and induces apoptosis.

Abstract: A symmetrical macrocyclic dizinc(II) complex (1) has been synthesized by using the ligand (L1) [μ-11,24-dimethyl-4,7,16,19-tetraoxa-3,8,15,20-tetraazatricyclo-[20.3.1.110,13] heptacosa-1(25),2,7,9,11,13(27),14,20,22(26),23-decaene-26,27-diol]. A series of unsymmetrical macrocyclic dizinc(II) complexes (2–6) has been synthesized by Schiff base condensation of bicompartmental mononuclear complex [ZnL] [μ-3,16-dimethyl-8,11-dioxa-7,12-diazadicyclo-[1.114,18] heptacosa-1,3,5(20),6,12,14,16,18(19)-octacaene-19,20-diolato)zinc(II)] with various diamines like 1,2-diamino ethane (L2), 1,3-diamino propane (L3), 1,4-diamino butane (L4), 1,2-diamino benzene (L5), and 1,8-diamino naphthalene (L6). The ligand L1 and all the zinc(II) complexes were structurally characterized. To corroborate the consequence of the aromatic moiety in comparison to the aliphatic moiety present in the macrocyclic ring on the phosphate ester hydrolysis, DNA binding and cleavage properties have been studied. The observed first order rate con...

Strontium-Substituted Calcium Deficient Hydroxyapatite Nanoparticles: Synthesis, Characterization, and Antibacterial Properties

Abstract: Strontium-substituted apatites have provoked increased interest in recent years for their beneficial effects on osteoporotic bone treatment and replacement. In this study, rod- and acicular-shaped, strontium-substituted calcium deficient hydroxyapatite (CDHA) nanoparticles with (Ca + Sr)/P ratio of 1.61 were synthesized via accelerated microwave processing. The X-ray powder diffraction analysis indicates the synthesized nanoparticles as apatite phase with diffraction patterns similar to those of hydroxyapatite. The hydrodynamic diameter of the particles were observed to be ~200–500 nm and found to increase with strontium substitution along with an increase in the negative zeta potential by dynamic light scattering method, suggesting the particles to be agglomerates in water. The morphology of the nanoparticles was studied using transmission electron microscopy (TEM), where, pure CDHA showed globular and strontium substituted CDHAs showed rod and acicular shape for 5% and 10% Sr substitution, respectively. The average size of the particles in TEM was measured to be 33 nm × 5 nm, 40 nm × 6 nm, and 55 nm × 8 nm (L × W) for pure and strontium-substituted CDHAs, respectively. Inductively coupled plasma spectroscopy, energy dispersive X-ray analysis, and Fourier transform infrared spectroscopy further confirm the substitution of strontium and deficiency of calcium in the synthesized nanoparticles. Thermal stability and in vitro solubility of CDHA nanoparticles were observed to increase with strontium substitution. The MTT [3-(4, 5-Dimethylthiazole-2-yl)-2, 5-diphenyl tetrazolium bromide] assay indicate that the substituted nanoparticles are non-toxic to human periodontal ligament fibroblast (HPDLF) cells. Cell uptake study by fluorescence microscopy using rhodamine-123 and actin/DAPI stained HPDLF cells show cellular localization of the nCDHA, nSr5CDHA, nSr10CDHA nanoparticles without any adverse effects. The strontium-substituted CDHAs showed significant antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria by colony count method. The 10% Sr substituted CDHA show the maximum microbial reduction of around 56% for E. coli and 35% for S. aureus with 1 × 105 cells/mL of respective bacterial culture.

Assessing community resilience to climate-related disasters in Chennai, India

Abstract: This article compares the resilience of two communities in Chennai, India, to climate-related disasters. The selected communities have similar exposure to natural hazards (cyclones and river-based floods due to their close proximity to the sea. Both areas are predominantly residential. Results from a household survey, assessing the physical, social and economic resilience of individuals through a Climate-related Disaster Community Resilience Framework (CDCRF), reveal that people living in the vicinity of rivers and canals are at higher risk from impacts (damages on house, diseases) of floods compared to others. However, despite their experience to past flood-related disasters, they have not been able to enhance their coping capacity due to their limited adaptive capacity. Thus, their resilience is limited to absorb, manage and bounce back future climate-related disasters (particularly floods). In collaboration with other stakeholders, mainly the Corporation of Chennai (Municipality), community-driven participatory solutions are concluded to have beneficial effect in enhancing the resilience of communities to climate-related disasters.

Efficacy and safety of three antiretroviral regimens for initial treatment of HIV-1: a randomized clinical trial in diverse multinational settings.

Abstract: Background Antiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world. Methods and Findings 1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72–1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54–0.76; p<0.001) and there was a significant interaction between sex and regimen safety (HR 0.50, CI 0.39–0.64 for women; HR 0.79, CI 0.62–1.00 for men; p = 0.01). Comparing ATV+DDI+FTC to EFV+3TC-ZDV, during a median follow-up of 81 wk there were 108 failures (21%) among 526 participants assigned to ATV+DDI+FTC and 76 (15%) among 519 participants assigned to EFV+3TC-ZDV (HR 1.51, CI 1.12–2.04; p = 0.007). Conclusion EFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen. Trial Registration www.ClinicalTrials.gov NCT00084136 Please see later in the article for the Editors' Summary.

Synthesis and Characterization of Rare Earth Ion Doped Nano ZnO

Abstract: Zinc oxide (ZnO) doped with erbium at different concentrations was synthesized by solid-state reaction method and characterized by X-ray diffraction (XRD), scanning electron microscopic (SEM), UV-absorption spectroscopy, photoluminescence (PL) study and vibrating sample magnetometer. The XRD studies exhibit the presence of wurtzite crystal structure similar to the parent compound ZnO in 1% Er3+ doped ZnO, suggesting that doped Er3+ ions sit at the regular Zn2+ sites. However, same studies spread over the samples with Er3+ content>1% reveals the occurrence of secondary phase. SEM images of 1% Er3+ doped ZnO show the polycrystalline nature of the synthesized sample. UV-visible absorption spectrum of Er3+ doped ZnO nanocrystals shows a strong absorption peak at 388 nm due to ZnO band to band transition. The PL study exhibits emission in the visible region, due to excitonic as well as defect related transitions. The magnetization-field curve of Er3+ doped ZnO nanocrystals showed ferromagnetic property at room-temperature.

Failure to prescribe pneumocystis prophylaxis is associated with increased mortality, even in the cART era: results from the Treat Asia HIV observational database.

Abstract: Pneumocystis jiroveci pneumonia (PCP) prophylaxis is recommended for patients with CD4 counts of less than 200 cells/mm3. This study examines the proportion of patients in the TREAT Asia HIV Observational Database (TAHOD) receiving PCP prophylaxis, and its effect on PCP and mortality.

Hesperidin-mediated expression of Nrf2 and upregulation of antioxidant status in senescent rat heart

Abstract: Objectives Oxidative stress is recognized as a key element responsible for the development of age-related pathologies A declining endogenous defence system during senescence dictates the need for supplementation with exogenous antioxidants through diet Hesperidin is a naturally occurring flavonone present in citrus fruits and has been shown to have many biological properties, including antioxidant activity We investigated whether hesperidin supplementation could be valuable in protecting cardiac tissue of aged rats against age-related increase in oxidative stress, as well as the mechanism by which it can boost the antioxidant status of the cell Methods The activity of antioxidant enzymes, mRNA expression of Nrf2, protein levels of superoxide dismutase and catalase were measured using standard protocols Key findings Hesperidin treatment effectively protected aged rat heart by increasing the activity of enzymic antioxidants Hesperidin upregulated the protein levels of nuclear factor erythroid 2-related factor 2, which is responsible for maintaining the antioxidant status of the cell Conclusions Hesperidin could be useful in protecting cardiomyocytes against age-related increase in oxidative stress mediated by Nrf2 upregulation

Homology modeling, molecular dynamics, e-pharmacophore mapping and docking study of Chikungunya virus nsP2 protease

Abstract: To date, no suitable vaccine or specific antiviral drug is available to treat Chikungunya viral (CHIKV) fever. Hence, it is essential to identify drug candidates that could potentially impede CHIKV infection. Here, we present the development of a homology model of nsP2 protein based on the crystal structure of the nsP2 protein of Venezuelan equine encephalitis virus (VEEV). The protein modeled was optimized using molecular dynamics simulation; the junction peptides of a nonstructural protein complex were then docked in order to investigate the possible protein-protein interactions between nsP2 and the proteins cleaved by nsP2. The modeling studies conducted shed light on the binding modes, and the critical interactions with the peptides provide insight into the chemical features needed to inhibit the CHIK virus infection. Energy-optimized pharmacophore mapping was performed using the junction peptides. Based on the results, we propose the pharmacophore features that must be present in an inhibitor of nsP2 protease. The resulting pharmacophore model contained an aromatic ring, a hydrophobic and three hydrogen-bond donor sites. Using these pharmacophore features, we screened a large public library of compounds (Asinex, Maybridge, TOSLab, Binding Database) to find a potential ligand that could inhibit the nsP2 protein. The compounds that yielded a fitness score of more than 1.0 were further subjected to Glide HTVS and Glide XP. Here, we report the best four compounds based on their docking scores; these compounds have IDs of 27943, 21362, ASN 01107557 and ASN 01541696. We propose that these compounds could bind to the active site of nsP2 protease and inhibit this enzyme. Furthermore, the backbone structural scaffolds of these four lead compounds could serve as building blocks when designing drug-like molecules for the treatment of Chikungunya viral fever.

Synergistic anticancer activity of curcumin and catechin: An in vitro study using human cancer cell lines

Abstract: The most practical approach to reduce morbidity and mortality of cancer is to delay the process of carcinogenesis by usage of anticancer agents. This necessitates that safer compounds are to be critically examined for anticancer activity especially, those derived from natural sources. A spice commonly found in India and the surrounding regions, is turmeric, derived from the rhizome of Curcuma longa and the major active component is a phytochemical termed curcumin. Green tea is one of the most popular beverages used worldwide, produced from the leaves of evergreen plant Camellia sinensis and the major active ingredients are polyphenolic compounds known as catechins. In this study, synergistic anticancer activity of curcumin and catechin was evaluated in human colon adenocarcinoma HCT 15, HCT 116, and human larynx carcinoma Hep G-2 cell lines. Although, both curcumin or catechin inhibited the growth of above cell lines, interestingly, in combination of both these compounds highest level of growth control was observed. The anticancer activity shown is due to cytotoxicity, nuclear fragmentation as well as condensation, and DNA fragmentation associated with the appearance of apoptosis. These results suggest that curcumin and catechin in combination can inhibit the proliferation of HCT 15, HCT 116, as well as Hep G-2 cells efficiently through induction of apoptosis.

Synthesis and characterization of silver nanoparticles supported on surface-modified poly(N-vinylimidazale) as catalysts for the reduction of 4-nitrophenol

Abstract: Two types of bead-shaped stable heterogeneous nanoparticle catalysts, viz. polymer-supported poly(styrene) functionalized with poly(vinylimidazole) immobilized silver nanoparticles (PS-PVIm-AgNPs) were prepared from poly(styrene)-co-poly( N -vinylimidazole) polymer matrices derived from 2% (Type-I) and 10% (Type-II) cross-linking monomer divinylbenzene and AgNO 3 as a metal precursor. The appearance of surface plasmon resonance peak at 422 nm in UV and Ag N (str,ring) peaks noticed at 1664 cm −1 for Type-I and 1668 cm −1 for Type-II catalysts in FT-IR confirms the immobilization of AgNPs onto PS-PVIm. The SEM and EDAX results prove that the Type-I catalyst has heterogeneous morphology with more white patches and enhanced amount of surface nitrogen and AgNPs than Type-II. The size of the AgNPs on Type-I and Type-II catalysts was measured as 10 nm and 14.6 nm from XRD, respectively. The comparative catalytic study for the reduction of 4-nitrophenol reveals that the pseudo-first order rate constant ( k obs ) for Type-I catalyst was relatively superior ( k obs = 5.12 × 10 −4 ) than Type-II ( k obs = 1.20 × 10 −4 ) due to the addition of high cross-linking load in Type-II. For the same reaction with Type-I catalyst, the variation of [substrate], [catalyst] and [NaBH 4 ] was directly proportional to k obs . The stability and reusability of the catalyst were observed good and sustained even at six cycles.

Emergence of Klebsiella pneumoniae isolate co-producing NDM-1 with KPC-2 from India

Abstract: Sir, The emergence of NDM-1-producing isolates and their sources have been clearly identified in several countries worldwide. In particular, the blaNDM-1 gene was identified in various genera of Enterobacteriaceae and in non-fermenting Gram-negative bacilli from environmental samples in India. Furthermore, the increasing co-production of NDM-1 with other carbapenemases has been detected amongst isolates of Enterobacteriaceae and Acinetobacter sp. in many parts of India. – 7 We report here the isolation of a strain of Klebsiella pneumoniae (designated IR98) from a urine sample from a middle-aged patient admitted to the intensive care unit of a tertiary care hospital in Chennai, India in July 2010. Species identification and antibiotic susceptibility, determined using an automated system (VITEK-2, bioMerieux Inc.), showed wide-spectrum resistance to b-lactams, aminoglycoside, fluoroquinolones, co-trimoxazole, nitrofurantoin and tigecycline, but susceptibility to colistin and fosfomycin, according to CLSI guidelines. MICs of various antibiotics were determined using the agar dilution method, while the tigecycline MIC was determined using the broth microdilution method. European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints were applied to interpret the susceptibilities. The isolate was highly resistant to imipenem (256 mg/L), meropenem (128 mg/L), ceftazidime (.256 mg/L), cefotaxime (.256 mg/L), amikacin (.512 mg/L), gentamicin (.512 mg/L), tobramycin (.512 mg/L), netilmicin (.512 mg/L), co-trimoxazole (.32 mg/L), ciprofloxacin (.32 mg/L) and tigecycline (4 mg/L), but remained susceptible to colistin (0.5 mg/L). The double-disc synergy test (DDST), modified Hodge test (MHT) and combined-disc synergy test (CDST) were used for the detection of metallo-b-lactamases (MBLs), other carbapenemases and KPC, or KPC with MBLs. The simultaneous production of MBL and KPC-like carbapenemases was confirmed by positive DDST, MHT and CDST with meropenem discs containing both EDTA and phenylboronic acid (PBA) or EDTA, while meropenem discs supplemented with PBA were negative. PCR assays for genes encoding b-lactamases and 16S rRNA methylases revealed the presence of blaNDM-1, blaKPC-2, blaCTX-M-15, blaSHV-12, blaTEM-1, blaOXA-1 and rmtB genes. Plasmid analysis using the Kieser technique revealed that K. pneumoniae IR98 harboured four plasmids, with sizes of 160, 120, 70 and 40 kb, using Escherichia coli NCTC 50192 as a reference. To study the transferability of these plasmids (encoding the resistance determinants), transconjugation and transformation experiments were performed using E. coli J53 (Azide-R) and E. coli TOP10 as recipient strains. Transconjugants were selected on MacConkey agar plates using sodium azide (200 mg/L) with ceftazidime (2 mg/L), meropenem (0.5 mg/L) or amikacin (20 mg/L). The plasmid extract of K. pneumoniae IR98 was transformed into E. coli TOP10, and transformants were selected on MacConkey agar plates containing 2 mg/L ceftazidime. Selected colonies were replica-plated onto MacConkey agar plates with or without meropenem (0.5 mg/L) or amikacin (20 mg/L). The genes encoding NDM-1, CTX-M15 and 16S rRNA methylase were transferred in conjugation experiments, whereas transfer of KPC-2 was successful only by transformation. The plasmids purified from the clinical isolate, transconjugants and transformants were typed by PCR-based replicon typing (PBRT). The E. coli J53-p98A transconjugant obtained from the meropenem plate showed an MBL phenotype and elevated MICs of all the b-lactams (except aztreonam) and susceptibility to non-b-lactam antibiotics. Plasmid analysis revealed that E. coli J53-p98A harboured a 160 kb plasmid that belonged to the Inc A/C type. Subsequently, this plasmid was found by PCR to carry the blaNDM-1 gene. In addition, the E. coli J53-p98B transconjugant grown on both ceftazidime and amikacin plates showed decreased susceptibility to aminoglycosides and cephalosporins except cefoxitin, and was positive for extendedspectrum b-lactamase (ESBL) production on DDST. Both blaCTX-M15 and rmtB genes were carried on a 120 kb IncF plasmid that was identified in E. coli J53-p98B. In contrast, the ESBL-negative transformant (E. coli TOP10-p98C) from both ceftazidime and meropenem plates was resistant to all the b-lactams except carbapenems (MICs 2 mg/L). The blaKPC-2 gene together with blaTEM-1 was carried on a 70 kb non-typeable plasmid that was identified in E. coli TOP10-p98C. Although the co-existence of blaNDM-1 with different carbapenemase genes has been reported in India, we believe this to be the first report of the co-occurrence of blaNDM-1 with blaKPC-2 and rmtB in a clinical isolate of K. pneumoniae from India. This co-production of NDM-1 with an unrelated carbapenemase and 16S RNA methylase results in very broad-spectrum antibiotic resistance profiles. The growing emergence of these powerful resistance mechanisms in India is cause for great concern as treatment options are virtually exhausted.

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

Abstract: This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Ameliorating Effect of Fish Oil on Acrylamide Induced Oxidative Stress and Neuronal Apoptosis in Cerebral Cortex

Abstract: Acrylamide (ACR) is a known industrial toxic chemical that produce neurotoxicity characterized by progressive neuronal degeneration. This study was designed to investigate the protective effect of fish oil on ACR-induced neuronal damage in Wistar rats. ACR enhances the production of reactive oxygen species and potentially affects brain. ACR administered rats showed increased levels of lipid peroxidative product, protein carbonyl content, hydroxyl radical and hydroperoxide which were significantly modulated by the supplementation of fish oil. The activities of enzymic antioxidants and levels of reduced glutathione were markedly lowered in ACR-induced rats; fish oil treatment augmented these antioxidant levels in cortex. Free radicals generated during ACR administration reduced the activities of membrane adenosine triphosphatases and acetylcholine esterase. Fish oil enhanced the activities of these enzymes near normal level. Histological observation represented the protective role of fish oil in ACR-induced neuronal damage. Fish oil reduced the ACR-induced apoptosis through the modulation in expressions of B-cell lymphoma 2 (Bcl2)-associated X protein and Bcl2-associated death promoter. Further, fish oil increases the expression of heat shock protein 27 (Hsp27) in ACR-induced rats. This study provides evidence for the neuroprotective effect of fish oil on ACR-induced neurotoxicity by reducing oxidative stress and apoptosis with modulation in the expression of Hsp27.

Capsaicin inhibits benzo(a)pyrene-induced lung carcinogenesis in an in vivo mouse model.

Abstract: Lung cancer is a serious health problem in most developed countries and its incidence rate is profusely increasing. Capsaicin, a component of red chilli and red pepper has been studied widely for its chemopreventive properties. The aim of the present study is to explore the anti-tumor activity of capsaicin against benzo(a)pyrene-induced lung tumorigenesis in Swiss albino mice. Benzo(a)pyrene was administered orally (50 mg/kg body weight) to induce lung cancer in Swiss albino mice. Hematological study (hemoglobin content, RBC, WBC count and differential count), histochemical analysis of mast cells and Western blot analysis of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and nuclear factor-kappa B (NF-κB) were carried out. Hematological parameters and the histochemical analysis of mast cells showed abnormal changes, and the immunoblotting analysis revealed increased protein expression of TNF-α, IL-6, COX-2 and NF-κB in lung cancer-challenged mice administered with benzo(a)pyrene. Capsaicin (10 mg/kg body weight) supplementation to lung cancer bearing mice considerably prevented all the above abnormalities. The results of the present study indicate the protective effect of capsaicin against benzo(a)pyrene-induced lung carcinogenesis in mice.