Suraj Singh Yadav

Immunomodulatory role of Emblica officinalis in arsenic induced oxidative damage and apoptosis in thymocytes of mice.

BackgroundArsenic is widely distributed in the environment and has been found to be associated with the various health related problems including skin lesions, cancer, cardiovascular and immunological disorders. The fruit extract of Emblica officinalis (amla) has been shown to have anti-oxidative and immunomodulatory properties. In view of increasing health risk of arsenic, the present study has been carried out to investigate the protective effect of amla against arsenic induced oxidative stress and apoptosis in thymocytes of mice.MethodsMice were exposed to arsenic (sodium arsenite 3 mg/kg body weight p.o.) or amla (500 mg/kg body weight p.o.) or simultaneously with arsenic and amla for 28 days. The antioxidant enzyme assays were carried out using spectrophotometer and generation of ROS, apoptotic parameters, change in cell cycle were carried out using flow cytometer following the standard protocols.ResultsArsenic exposure to mice caused a significant increase in the lipid peroxidation, ROS production and decreased cell viability, levels of reduced glutathione, the activity of superoxide dismutase, catalase, cytochrome c oxidase and mitochondrial membrane potential in the thymus as compared to controls. Increased activity of caspase-3 linked with apoptosis assessed by the cell cycle analysis and annexin V/PI binding was also observed in mice exposed to arsenic as compared to controls. Co-treatment with arsenic and amla decreased the levels of lipid peroxidation, ROS production, activity of caspase-3, apoptosis and increased cell viability, levels of antioxidant enzymes, cytochrome c oxidase and mitochondrial membrane potential as compared to mice treated with arsenic alone.ConclusionsThe results of the present study exhibits that arsenic induced oxidative stress and apoptosis significantly protected by co-treatment with amla that could be due to its strong antioxidant potential.

High Serum Level of Matrix Metalloproteinase 9 and Promoter Polymorphism − 1562 C:T as a New Risk Factor for Metabolic Syndrome

The altered matrix metalloproteinases (MMPs) have been suggested in the pathophysiology of metabolic syndrome (MetS). Genetic variants in the promoter region of MMP1 and MMP9 genes may modulate an individuals susceptibility to MetS. The aim of this study was to determine the frequency of MMP1 -519 A:G and MMP9 -1562 C:T polymorphisms and the correlation with serum levels of MMP1 and MMP9 in MetS susceptibility. On the basis of anthropometric profile and laboratory investigations, 180 confirmed MetS patients and 190 unrelated healthy controls of similar ethnicity were genotyped for MMP1 -519 A:G and MMP9-1562 C:T polymorphisms by using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. In addition, serum levels of MMP1 and MMP9 were quantified by ELISA. We found that the serum level of MMP9 was significantly higher in MetS patients. Variant genotype TT of MMP9 -1562 demonstrated increased risk (odds ratio [OR]=3.70, p=0.015) of MetS. Similarly, variant allele T (OR=1.77, p=0.002) and combined genotype CT+TT (OR=1.81, p=0.057) also showed a significantly higher risk. The CT and TT genotypes of MMP9 -1562 polymorphism contributed to high serum levels of MMP9 in MetS patients. However, no such association was observed with the MMP1 serum level and -519 A:G polymorphism. Our results suggest that a higher serum level of MMP9 in the presence of MMP9 polymorphism -1562 C:T might be a risk factor for the development of MetS. The MMP9 enzyme activity might be a significant indicator in the screening of MetS patients.

Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice

Introduction: Arsenic, an environmental contaminant naturally occurred in groundwater and has been found to be associated with immune-related health problems in humans. Objective: In view of increasing risk of arsenic exposure due to occupational and non-occupational settings, the present study has been focused to investigate the protective efficacy of amla against arsenic-induced spleenomegaly in mice. Results: Arsenic exposures (3 mg/kg body weight p.o for 30 days) in mice caused an increase production of ROS (76%), lipid peroxidation (84%) and decrease in the levels of superoxide dismutase (53%) and catalase (54%) in spleen as compared to controls. Arsenic exposure to mice also caused a significant increase in caspases-3 activity (2.8 fold) and decreases cell viability (44%), mitochondrial membrane potential (47%) linked with apoptosis assessed by the cell cycle analysis (subG1-28.72%) and annexin V/PI binding in spleen as compared to controls. Simultaneous treatment of arsenic and amla (500 mg/kg body weight p.o for 30 days) in mice decreased the levels of lipid peroxidation (33%), ROS production (24%), activity of caspase-3 (1.4 fold), apoptosis (subG 1 12.72%) and increased cell viability (63%), levels superoxide dismutase (80%), catalase (77%) and mitochondrial membrane potential (66%) as compared to mice treated with arsenic alone. Conclusions: Results of the present study indicate that the effect of arsenic is mainly due to the depletion of glutathione in liver associated with enhanced oxidative stress that has been found to be protected following simultaneous treatment of arsenic and amla.

Significance of impaired serum gelatinases activities in metabolic syndrome

Introduction: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. Materials and Methods: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control. Results: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. Conclusions: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Vascular Endothelial Growth Factor 936 C>T Polymorphism Increased Oral Cancer Risk: Evidence from a Meta-Analysis

AIM The vascular endothelial growth factor (VEGF) plays a major role in angiogenesis. The association between VEGF 936 C>T (rs3025039) gene polymorphisms and oral cancer (OC) risk is still contentious and ambiguous. To assess the relationship between the VEGF 936 C>T genotype and the risk of developing OC, we performed a meta-analysis to summarize the possible association. METHODOLOGY We assessed published studies of the association between 936 C>T polymorphisms and OC risk from four studies with 440 controls and 556 OC cases. We calculated pooled odds ratios (ORs) and 95% confidence interval (CI), considering the frequency of allele, homozygous, heterozygous genotypes and comparison of dominant and recessive genetic models. RESULTS The combined results showed that the T allele was significantly associated with increased OC risk (T vs. C: p=0.001; OR=1.521, 95% CI=1.194-1.938). The heterozygous genotype CT had a 1.5-fold increased risk (CT vs. CC: p=0.002; OR=1.582, 95% CI=1.184-2.114). In addition the dominant genetic model demonstrated a 1.6-fold increased risk of developing OC (TT+CT vs. CC: p=0.001; OR=1.621, 95% CI=1.226-2.143). CONCLUSION Our results suggest that the VEGF gene polymorphism (936 C>T) contributes increased susceptibility to OC. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.

Genetic variants of matrix metalloproteinase (MMP2) gene influence metabolic syndrome susceptibility.

AIM Matrix metalloproteinases (MMPs) are suggested to be involved in the development of various clinical factors of metabolic syndrome (MetS). Allelic variants in the promoter region of the MMP2 gene may modulate an individuals susceptibility to MetS. We performed this study to determine whether single-nucleotide polymorphisms (SNPs) -1575 (G>A) and -168 (G>T) of the MMP2 gene are associated with MetS risk. METHODS In this hospital-based case-control study, 180 confirmed MetS patients and 190 unrelated healthy controls of similar ethnicity were genotyped for MMP2 (-1575 G>A, -168 G>T) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. RESULTS Variant genotype (AA) of -1575 showed increased risk (odds ratio [OR]=2.72, 95% confidence intervals [CI]=1.19-6.23, p=0.018) of MetS as compared to the wild-type homozygous genotype (GG). Similarly, the variant allele (A) (OR=1.60, 95%CI=1.12-2.26, p=0.009) and combined genotype (GA+AA) (OR=1.51, 95%CI=0.98-2.31, p=0.057) were also significantly associated with MetS risk. High risk of MetS was observed with respect to the haplotype (A-T) (OR=1.83, 95%CI=1.03-3.26, p=0.038) of MMP2 (-1575 and -168) polymorphisms. However, MMP2 (-168 G>T) polymorphism individually did not show any risk with MetS. CONCLUSIONS Our results strongly support the notion that common sequence variants and haplotype of MMP2 (-1575 G>A and -168 G>T) might be a genetic risk for the development of MetS in the North Indian population. Additional studies on larger populations are needed to clarify the role of genetic variants of this gene in MetS.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population.

Traditional knowledge to clinical trials: A review on therapeutic actions of Emblica officinalis

Plants are the integral part of the traditional indigenous healthcare system and are becoming concrete source of new drug discovery, evident by the increasing numbers of modern drugs derived from the phytochemicals. Emblica officinalis Gaertn. or Phyllanthus emblica Linn (family Phyllanthaceae) has been explained extensively and well documented for its therapeutic efficacies in indigenous system of medicine, in India. Every part of this plant possesses high medicinal value but fruits are the most valuable part in folklore and therapeutic uses. The polyphenols found in E.officinalis, especially tannins and flavonoids are key responsible elements for major bioactivities. E.officinalis is one of the major component in various health tonics, also exerts synergistic effects in enhancing the medicinal efficacy. E.officinalis exhibits broad spectrum of pharmacological activities through various mode of actions including antioxidant, anticancer, immunomodulator, anti-inflammatory, cyto-protective properties etc. Medical practitioners across the globe also advocated its application in managing diabetes, dyslipidemia, obesity, several types of cancer, liver disorders, arthritis, gingivitis, wound healing etc. The present review analysed and summarized the pharmacological actions, experimental studies and clinical trials of E. officinalis with emphasis on its immuno-enhancer, antiinflammatory and anticancer activities and possible mechanism of actions to provide future directions in translating these findings clinically.

Comparative Effect of Insulin Sensitizers and Statin on Metabolic Profile and Ultrasonographical Score in Non Alcoholic Fatty Liver Disease.

INTRODUCTION Non Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder involving fat accumulation in the liver. The initial management for patients with NAFLD includes lifestyle modification and weight loss in overweight or obese patients. AIM The present study was conducted to compare the efficacy of insulin sensitizers and statin in the patients of NAFLD. MATERIALS AND METHODS The study included 98 patients diagnosed with NAFLD on USG (Ultrasonography) abdomen, divided into three Groups randomly and administered Metformin (Group I), Rosuvastatin (Group II) or Pioglitazone (Group III) along with dietary intervention and lifestyle modification. Their Body Mass Index (BMI), liver function tests, fasting lipid profile, USG scores for fatty liver were done and followed up at 4 weeks, 12 weeks and 24 week for change in above parameters. RESULTS Out of the three Groups, Group II showed a maximum improvements in usg scores for NAFLD (p<0.001) and fasting lipid profile. Group II also showed maximum derangement of liver enzymes at 24 weeks though none of the subjects had more than three times elevation of liver enzymes. CONCLUSION Rosuvastatin may be an effective therapy as add on treatment to dietary and lifestyle intervention in patients of NAFLD. As an add-on treatment Rosuvastatin was superior to Pioglitazone or Metformin and acute decompensation is unlikely with this drug. Metformin was not effective as add on therapy for NAFLD, rather rapid weight loss in short period of time resulted in worsening of hepatic steatosis.

PATTERNS OF ERYTHROPOEISIS AND ANAEMIA IN LEPROSY

A total of 128 leprosy patients were investigated for the morphological type of anaemia, the underlying disturbances in iron metabolism and patterns of erythropoiesis and other cytomorphological changes in the bone marrow. The anaemia was a mild to moderate degree in paucibacillary (PB) leprosy, while in multibacillary (MB) leprosy it was of a severe degree. Iron deficiency was observed in only a few patients. Impaired iron utilization as observed in a anaemia of a chronic disorder was a common finding in MB leprosy (41.7%) and more so in new cases (50%). Megaloblastic erythropoiesis was also more frequent in MB leprosy (45.2%) as compared to PB leprosy (16%), accounting for the severe degree of anaemia in the former type. In 17.2% of the total patients (MB, 21.4%; PB, 9%) both megaloblastic erythropoiesis and features of impaired iron utilization were observed in bone marrow. Disturbances in iron metabolism and erythropoiesis were also observed but to a lesser degree in patients receiving specific antileprosy treatment. Irrespective of the type of disease and duration of treatment, increasing frequency of acid-fast bacillia (AFB) positivity and granulomas was observed in the bone marrow with an increasing severity of anaemia.