Influence of glutathione-related genetic variants on the oxidative stress profile of Mexican patients with psychotic disorders

Objective: The clinical trajectories of patients with psychotic disorders have divergent outcomes, which may result in part from glutathione (GSH)-related high-risk genotypes. We aimed to determine pharmacokinetics of clozapine, GSH levels, GSH peroxidase (GPx) activity, gene variants involved in the synthesis and metabolism of GSH, and their association with psychotic disorders in Mexican patients on clozapine monotherapy and controls. Methods: The sample included 75 patients with psychotic disorders on clozapine therapy and 40 paired healthy controls. Plasma clozapine/N-desmethylclozapine, GSH concentrations, and GPx activity were determined, along with genotyping of GCLC and GSTP1 variants and copy number variations of GSTP1, GSTT1, and GSTM1. Clinical, molecular and biochemical data were analyzed with a logistic regression model. Results: GSH levels were significantly reduced and, conversely, GPx activity was higher among patients than controls. GCLC_GAG-7/9 genotype (OR = 4.3, 95%CI = 1.40-14.31, p = 0.019) and hetero-/homozygous genotypes of GCLC_rs761142 (OR = 6.09, 95%CI = 1.93-22.59, p = 0.003) were found to be risk factors for psychosis. The genetic variants were not related to clozapine/N-desmethylclozapine levels or metabolic ratio. Conclusions: GCLC variants were associated with the oxidative stress profile of patients with psychotic disorders, raising opportunities for intervention to improve their antioxidant defenses. Further studies with larger samples should explore this proposal.

Impact of dietary oils and fats on lipid peroxidation in liver and blood of albino rats

Objective:To investigate the effects of different dietary fat and oils (differing in their degree of saturation and unsaturation) on lipid peroxidation in liver and blood of rats. Methods:The study was conducted on 50 albino rats that were randomly divided into 5 groups of 10 animals. The groups were fed on dietary butter (Group I), margarine (Group II), olive oil (Group III), sunflower oil (Group IV) and corn oil (Group V) for 7 weeks. After 12 h of diet removal, livers were excised and blood was collected to measure malondialdehyde (MDA) levels in the supernatant of liver homogenate and in blood. Blood superoxide dismutase activity (SOD), glutathione peroxidase activity (GPx), serum vitamin E and total antioxidant capacity (TAC) levels were also measured to determine the effects of fats and oils on lipid peroxidation. Results: The results indicated that no significant differences were observed in SOD activity, vitamin E and TAC levels between the five groups. However, there was significant decrease of GPx activity in groups IV and V when compared with other groups. The results indicated that feeding corn oil caused significant increases in liver and blood MDA levels as compared with other oils and fats. There were positive correlations between SOD and GPx, vitamin E and TAC as well as between GPx and TAC (r:0.743;P Conclusions:The results demonstrated that feeding oils rich in polyunsaturated fatty acids (PUFA) increases lipid peroxidation significantly and may raise the susceptibility of tissues to free radical oxidative damage.

Impact of dietary oils and fats on lipid peroxidation in liver and blood of albino rats

<p><b>OBJECTIVE</b>To investigate the effects of different dietary fat and oils (differing in their degree of saturation and unsaturation) on lipid peroxidation in liver and blood of rats.</p><p><b>METHODS</b>The study was conducted on 50 albino rats that were randomly divided into 5 groups of 10 animals. The groups were fed on dietary butter (Group I), margarine (Group II), olive oil (Group III), sunflower oil (Group IV) and corn oil (Group V) for 7 weeks. After 12 h of diet removal, livers were excised and blood was collected to measure malondialdehyde (MDA) levels in the supernatant of liver homogenate and in blood. Blood superoxide dismutase activity (SOD), glutathione peroxidase activity (GPx), serum vitamin E and total antioxidant capacity (TAC) levels were also measured to determine the effects of fats and oils on lipid peroxidation.</p><p><b>RESULTS</b>The results indicated that no significant differences were observed in SOD activity, vitamin E and TAC levels between the five groups. However, there was significant decrease of GPx activity in groups IV and V when compared with other groups. The results indicated that feeding corn oil caused significant increases in liver and blood MDA levels as compared with other oils and fats. There were positive correlations between SOD and GPx, vitamin E and TAC as well as between GPx and TAC (r: 0.743; P<0.001) and between blood MDA and liver MDA (r: 0.897; P<0.001). The results showed also negative correlations between blood MDA on one hand and SOD, GPx, vitamin E and TAC on the other hand.</p><p><b>CONCLUSIONS</b>The results demonstrated that feeding oils rich in polyunsaturated fatty acids (PUFA) increases lipid peroxidation significantly and may raise the susceptibility of tissues to free radical oxidative damage.</p>

Effect of Age and Liver Cirrhosis on the Gluthathione Concentration and Glutathione Peroxidase Activity in the Plasma, Erythrocytes and Gastric Mucosa of Human

BACKGROUND: The role of aging in damage to DNA have been of increasing in recent years. DNA damage correlated with biochemical and physiologic changes that are characteristic of cellular impairment in aging and disease. Reduction of oxygen in tissue produces a number of oxygen free radicals which may induce cellular damage and even cell death. Glutathione, its function in reductive processes that are essential for the synthesis (and the degradation) of proteins, formation of deoxyribonucleotide precursors of DNA, regulation of enzymes, and protection of the cell against reactive oxygen compounds and free radicals. The aim of this study was, 1) to measure the glutathione concentration and glutathione proxidase activity of erythroyte, plasma, human gastric mucosa in elderly and liver cirrhosis patient 2) to investigate a role of glutathione mediated cellular defense mechanism against oxidative stress between in liver cirrhosis patient and in elderly. METHODS: We measured glutathione concentration and glutathione peroxidase activity in the plasma, erythrocytes, gastric mucosa of human in 4 group (Group A: 10 patients of liver cirrhosis and portal hypertensive gastropathy in age 40~55 years, Group B: same number and disease of patients in age over 65 years, group C: healthy person of age over 65 years, Group D: control). Glutathione concentration of erythocyte, plasma and human gastric mucosa was measured by spectrophotometer using Bioxytech GSH-400. Glutathione peroxidase activity of plasma was measured by Paglia & Valentine method using Bioxytech pl. Gpx and of erythocyte and human gastric mucosa was measured by using Bioxytech Gpx.340. Statistical significance of the different group was determined by ANOVA. A p<0.05 was considered significant. RESULT: Glutathione concentration of erythrocytes and gastric mucosa was decreased in Group A, B, C compared to group D. plasma concentration of glutathione was decreased in group A, B compared to group C, D. Activity of glutathione peroxidase was not different in any group (ANOVA, p<0.005). CONCLUSION: Even though glutathione concentration of erythrocyte and human gastric mucosa was decreased in elderly and in liver cirrhosis patient, our study shows decreased glutathione related defense mechanism against oxidative stress is different in view of plasma concentration of glutathione.