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1.
J Adv Res ; 8(3): 289-295, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28337346

RESUMO

The present study principally sought to investigate the effect of green tea extract (GTE) supplementation on hepatic mitochondrial DNA (mtDNA) damage in alcohol receiving rats. MtDNA was isolated from hepatic tissues of albino wistar rats after alcohol treatment with and without GTE supplementation. Entire displacement loop (D-loop) of mtDNA was screened by PCR-Sanger's sequencing method. In addition, mtDNA deletions and antioxidant activity were measured in hepatic tissue of all rats. Results showed increased frequency of D-loop mutations in alcoholic rats (ALC). DNA mfold analysis predicted higher free energy for 15507C and 16116C alleles compared to their corresponding wild alleles which represents less stable secondary structures with negative impact on overall mtDNA function. Interestingly, D-loop mutations observed in ALC rats were successfully restored on GTE supplementation. MtDNA deletions were observed in ALC rats, but intact native mtDNA was found in ALC + GTE group suggesting alcohol induced oxidative damage of mtDNA and ameliorative effect of GTE. Furthermore, markedly decreased activities of glutathione peroxidise, superoxide dismutase, catalase and glutathione content were identified in ALC rats; however, GTE supplementation significantly (P < 0.05) restored these levels close to normal. In conclusion, green tea could be used as an effective nutraceutical against alcohol induced mitochondrial DNA damage.

2.
J Clin Biochem Nutr ; 60(1): 63-69, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28163384

RESUMO

The present study aimed to understand the association between erythrocyte membrane alterations and hemolysis in chronic alcoholics. Study was conducted on human male volunteers aged between 35-45 years with a drinking history of 8-10 years. Results showed that plasma marker enzymes AST, ALT, ALP and γGT were increased in alcoholic subjects. Plasma and erythrocyte membrane lipid peroxidation, erythrocyte lysate nitric oxide (NOx) levels were also increased significantly in alcoholics. Furthermore, erythrocyte membrane protein carbonyls, total cholesterol, phospholipid and cholesterol/phospholipid (C/P) ratio were increased in alcoholics. SDS-PAGE analysis of erythrocyte membrane proteins revealed that increased density of band 3, protein 4.2, 4.9, actin and glycophorins, whereas glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and glycophorin A showed slight increase, however, decreased ankyrin with no change in spectrins (α and ß) and protein 4.1 densities were observed in alcoholics. Moreover, alcoholics red blood cells showed altered morphology with decreased resistance to osmotic hemolysis. Increased hemolysis showed strong positive association with lipid peroxidation (r = 0.703, p<0.05), protein carbonyls (r = 0.754, p<0.05), lysate NOx (r = 0.654, p<0.05) and weak association with C/P ratio (r = 0.240, p<0.05). Bottom line, increased lipid and protein oxidation, altered membrane C/P ratio and membrane cytoskeletal protein profile might be responsible for the increased hemolysis in alcoholics.

3.
Mitochondrial DNA A DNA Mapp Seq Anal ; 28(5): 632-637, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-27159714

RESUMO

Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species. In the present study, we sequenced the entire mitochondrial D-loop region (1124 bp) of colorectal cancer (CRC) patients (n = 174) and controls (n = 170) of south Indian origin to identify significant mutations/polymorphisms. Our results showed 152 polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (54.6%) than in II (45.4%) of D-loop region. The frequencies of 310'C' insertion (p = 0.0078), T16189C (p = 0.0097) variants and 310'C'ins/16189C haplotype (p = 0.0029) were significantly higher in cases than in controls. Furthermore, strong linkage disequilibrium was observed between nucleotide position 310 and 16189 in cases (D'=0.68) as compared with controls (D'=0.27). In conclusion, mitochondrial D-loop sequence alterations may constitute inherent risk factor for CRC.


Assuntos
Neoplasias Colorretais/genética , DNA Mitocondrial/genética , Polimorfismo de Nucleotídeo Único , Análise de Sequência de DNA/métodos , População Branca/genética , DNA Mitocondrial/química , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Índia , Desequilíbrio de Ligação , Masculino , Mitocôndrias/genética
4.
Biomed Pharmacother ; 84: 740-746, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27710898

RESUMO

The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na+/K+-ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage.


Assuntos
Etanol/toxicidade , Nefropatias/metabolismo , Nefropatias/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Pterocarpus , Animais , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Etanol/administração & dosagem , Nefropatias/induzido quimicamente , Masculino , Estresse Oxidativo/fisiologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Substâncias Protetoras/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar
5.
Pharmacogn Rev ; 10(19): 43-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27041873

RESUMO

Recently there has been increasing interest in plants and plant-derived compounds as raw food and medicinal agents. In Ayurveda, an Indian system of traditional medicine, a wide spectrum of medicinal properties of Pterocarpus santalinus is described. Many important bioactive phytocompounds have been extracted and identified from the heartwood of P. santalinus. Bioactive compounds typically occur in small amounts and have more subtle effects than nutrients. These bioactive compounds influence cellular activities that modify the risk of disease rather than prevent deficiency diseases. A wide array of biological activities and potential health benefits of P. santalinus have been reported, including antioxidative, antidiabetic, antimicrobial, anticancer, and anti-inflammatory properties, and protective effects on the liver, gastric mucosa, and nervous system. All these protective effects were attributed to bioactive compounds present in P. santalinus. The major bioactive compounds present in the heartwood of P. santalinus are santalin A and B, savinin, calocedrin, pterolinus K and L, and pterostilbenes. The bioactive compounds have potentially important health benefits: These compounds can act as antioxidants, enzyme inhibitors and inducers, inhibitors of receptor activities, and inducers and inhibitors of gene expression, among other actions. The present review aims to understand the pharmacological effects of P. santalinus on health and disease with "up-to-date" discussion.

6.
Tumour Biol ; 37(8): 10357-64, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26846100

RESUMO

Mitochondrial displacement loop (D-loop) is a hot spot for mitochondrial DNA (mtDNA) alterations that effects cellular reactive oxygen species (ROS) generation. Manganese-superoxide dismutase (Mn-SOD) is a major antioxidant enzyme that protects cells from ROS-mediated damage. In the present study, we investigated the relationship between sequence alterations of mitochondrial D-loop and Mn-SOD expression in colorectal cancer (CRC). Genotyping of entire mitochondrial D-loop (1124 bp) was carried out on mtDNA of analogous tumor and normal tissues from 35 CRC patients of south Indian origin by PCR-sequencing analysis. Tumor-specific large-scale mtDNA deletions and Mn-SOD expression was analyzed by PCR and Western blot analysis, respectively. We identified 87 polymorphisms in the D-loop region of tumor and/or control tissues. Polymorphisms were predominantly located in hypervariable region I (67.9 %) than in II (32.1 %) of D-loop. Significantly increased mtDNA microsatellite instability (mtMSI) [310'C' insertion (P = 0.00001) and T16189C (P = 0.0007)] and elevated Mn-SOD expression was observed in tumor tissues compared with controls. Interestingly, mtMSI was significantly high in tumors with Mn-SOD overexpression. Tumor-specific large-scale mtDNA deletions were not observed in CRC tissues. In conclusion, mtMSI and Mn-SOD overexpression are a common event in CRC. The analysis of mtMSI and/or Mn-SOD expression might help to identify patients at high risk for disease outcome, thereby helping to refine therapeutic decisions in CRC.


Assuntos
Adenocarcinoma/enzimologia , Adenocarcinoma/genética , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/genética , DNA Mitocondrial/genética , Superóxido Dismutase/biossíntese , Adenocarcinoma/patologia , Adulto , Idoso , Western Blotting , Neoplasias Colorretais/patologia , Feminino , Genótipo , Humanos , Masculino , Instabilidade de Microssatélites , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase
7.
Tumour Biol ; 35(12): 12059-67, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25146682

RESUMO

Cyclin D1 (CCND1) and E-cadherin (CDH1) are two important genes of the ß-catenin/LEF pathway that is involved in tumorigenesis of various cancers including colorectal cancer (CRC). However, studies of the association between genetic variants of these two genes and CRC have shown conflicting results. We conducted a genetic association study in South Indian population (cases, 103; controls, 107) to assess the association of CCND1 870G/A and CDH1 -160C/A single nucleotide polymorphisms (SNPs) with CRC risk. Genotyping of SNPs was performed by PCR sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D') for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of CCND1 and CDH1 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and adjacent normal tissues from 23 CRC patients by Western blot analysis. The frequencies of CCND1 870A/A (P = 0.045) genotype, CDH1 -160A allele (P = 0.042), and 870A/-160A haplotype (P = 0.002) were significantly higher in patients as compared with controls. Strong LD was observed between 870G/A and -160C/A SNPs in cases (D' = 0.76) as compared to controls (D' = 0.32). Furthermore, elevated CCND1 and diminished CDH1 expression was observed in tumor tissue as compared with analogous normal tissue of CRC patients. Interestingly, advanced-stage tumors showed wider expression alterations than in early-stage tumors. In conclusion, CCND1 870G/A and CDH1 -160C/A SNPs may modify the risk of CRC susceptibility in South Indian population. In addition, elevated CCND1 and diminished CDH1 expression appears to be useful prognostic markers for CRC.


Assuntos
Caderinas/genética , Neoplasias Colorretais/genética , Ciclina D1/genética , Predisposição Genética para Doença , Variação Genética , Adulto , Idoso , Alelos , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Genótipo , Haplótipos , Humanos , Índia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Análise de Sequência de DNA
8.
PLoS One ; 9(1): e85363, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24497926

RESUMO

BACKGROUND: Mitochondrial displacement loop (D-loop) is the hot spot for mitochondrial DNA (mtDNA) alterations which influence the generation of cellular reactive oxygen species (ROS). Association of D-loop alterations with breast cancer has been reported in few ethnic groups; however none of the reports were documented from Indian subcontinent. METHODOLOGY: We screened the entire mitochondrial D-loop region (1124 bp) of breast cancer patients (n = 213) and controls (n = 207) of south Indian origin by PCR-sequencing analysis. Haplotype frequencies for significant loci, the standardized disequilibrium coefficient (D') for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. PRINCIPAL FINDINGS: We identified 7 novel mutations and 170 reported polymorphisms in the D-loop region of patients and/or controls. Polymorphisms were predominantly located in hypervariable region I (60%) than in II (30%) of D-loop region. The frequencies of 310'C' insertion (P = 0.018), T16189C (P = 0.0019) variants and 310'C'ins/16189C (P = 0.00019) haplotype were significantly higher in cases than in controls. Furthermore, strong LD was observed between nucleotide position 310 and 16189 in controls (D' = 0.49) as compared to patients (D' = 0.14). CONCLUSIONS: Mitochondrial D-loop alterations may constitute inherent risk factors for breast cancer development. The analysis of genetic alterations in the D-loop region might help to identify patients at high risk for bad progression, thereby helping to refine therapeutic decisions in breast cancer.


Assuntos
Neoplasias da Mama/genética , DNA Mitocondrial/genética , Sequências Reguladoras de Ácido Nucleico , Sequência de Bases , Estudos de Casos e Controles , Análise Mutacional de DNA , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Humanos , Índia , Desequilíbrio de Ligação , Mutagênese Insercional , Mutação Puntual , Polimorfismo de Nucleotídeo Único , Fatores de Risco
9.
Alcohol Alcohol ; 48(6): 679-86, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23966453

RESUMO

AIM: The aim of the study was to elucidate the molecular mechanisms underlying the alcohol perturbation leading to deleterious effects on erythrocyte membrane transport in chronic alcoholics. METHODS: Membrane bound enzyme activities such as Na(+), K(+)-ATPase, Ca(2+),Mg(2+)-ATPase and acetylcholine esterase and membrane transport analysis by in vitro and erythrocyte membrane profile analysis in controls and chronic alcoholic red cells were analyzed. RESULTS: It was observed that decreased Na(+), K(+)-ATPase enzyme activity and increased activities of Ca(2+),Mg(2+)-ATPase and acetylcholine esterase in chronic alcoholics compared to controls. The in vitro studies of erythrocytes suggested that there is an increased uptake of glucose through chronic alcoholic red cells. However, glucose utilization by chronic alcoholic red cells was decreased. An increased sensitivity of ouabain for its binding site on Na(+), K(+)-ATPase in chronic alcoholic erythrocyte membrane was evident from this study. Though there appears to be an increased Na(+) influx in chronic alcoholic cells, the status of Na(+) transport is not altered much. However, ouabain caused slight disturbances in the transport of sodium, similar disturbances in the potassium transport resulting in much accumulation of potassium in red cells. CONCLUSIONS: It was concluded that chronic alcohol consumption modified certain membrane bound proteins, enzymes and transport mechanisms in chronic alcoholics.


Assuntos
Alcoolismo/sangue , Proteínas Sanguíneas/metabolismo , Proteínas de Transporte/metabolismo , Membrana Eritrocítica/química , Membrana Eritrocítica/efeitos dos fármacos , Proteínas de Membrana/análise , Acetilcolinesterase/sangue , Adenosina Trifosfatases/metabolismo , Adulto , Alcoólicos , Alcoolismo/enzimologia , Glicemia/análise , Glicemia/metabolismo , Proteínas Sanguíneas/análise , Proteínas de Transporte/análise , Eletroforese em Gel de Poliacrilamida , Inibidores Enzimáticos/farmacologia , Membrana Eritrocítica/enzimologia , Humanos , Masculino , Pessoa de Meia-Idade , Ouabaína/farmacologia , Potássio/sangue , Coloração pela Prata , Sódio/sangue
10.
Mol Cell Biochem ; 339(1-2): 35-42, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20047071

RESUMO

Ethanol disorders biological membranes causing perturbations in the bilayer and also by altering the physicochemical properties of membrane lipids. But, chronic alcohol consumption also increases nitric oxide (NO) production. There was no systemic study was done related to alcohol-induced production of NO and consequent formation of peroxynitrite mediated changes in biophysical and biochemical properties, structure, composition, integrity and function of erythrocyte membranes in chronic alcoholics. Hence, keeping all these conditions in mind the present study was undertaken to investigate the role of over produced nitric oxide on red cell membrane physicochemical properties in chronic alcoholics. Human male volunteers aged 44 +/- 6 years with similar dietary habits were divided into two groups, namely nonalcoholic controls and chronic alcoholics (~125 g of alcohol at least five times per week for the past 10-12 years). Elevated nitrite and nitrate levels in plasma and lysate, changes in erythrocyte membrane individual phospholipid composition, increased lipid peroxidation, protein carbonyls, cholesterol and phospholipids ratio (C/P ratio) and anisotropic value (gamma) with decreased sulfhydryl groups and Na(+)/K(+)-ATPase activity in alcoholics was evident from this study. RBC lysate NO was positively correlated with C/P ratio (r = 0.547) and anisotropic (gamma) value (r = 0.428), Na(+)/K(+)-ATPase activity was negatively correlated with RBC lysate NO (r = -0.372) and anisotropic (gamma) value (r = -0.624) in alcoholics. Alcohol-induced overproduction of nitric oxide reacts with superoxide radicals to produce peroxynitrite, which appears to be responsible for changes in erythrocyte membrane lipids and the activity of Na(+)/K(+)-ATPase.


Assuntos
Alcoólicos , Membrana Eritrocítica/efeitos dos fármacos , Etanol/efeitos adversos , Fluidez de Membrana/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Adulto , Doença Crônica , Membrana Eritrocítica/fisiologia , Humanos , Masculino , Fluidez de Membrana/fisiologia , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo
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