Leptin G-2548A and Leptin Receptor Q223R Gene Polymorphisms are Differently Associated with Oxidative Process in Mexican Mestizo and Indigenous with Obesity.

Leptin levels and oxidative stress are implicated in obesity risk. Reports of association of leptin gene (LEP) and leptin receptor gene (LEPR) polymorphisms with leptin elevation are contradictory in a diverse population. Only a few studies report the linkage of obesity with biochemical markers and genetic factors. OBJECTIVE: The aim of this study was to examine whether plasma lipid peroxidation, antioxidant capability, leptin levels are associate selected LEP -2548 A/G and LEPR Q223R polymorphisms in mestizo and indigenous obesity Mexican population. METHODS: We identified and characterized 50 overweight or obese subjects and 50 healthy, normal- weight volunteers with indigenous Tepehuana or Mexican mestizo ethnicity from Durango, Mexico. LEP -2548 A/G and LEPR Q223R polymorphisms were determined by genotyping. Concentrations of leptin, antioxidant capacity (CA) and lipoperoxidation (LIPX) were determined in fast conditions on plasma with Enzyme-Linked ImmunoSorbent Assay (ELISA) in all participants. RESULTS: The highest genotype frequency was the heterozygous LEPR, which was associated with lipid peroxidation levels in normal-weight Tepehuan populations. A positive correlation was observed (r = 0.5; p <0.01) between LEP polymorphism and lipoperoxidation in normal weight Tepehuan subjects. On the other hand, the LEPR polymorphism was associated with the level of lipoperoxidation (r = 0.13; P <0.05) in mestizo populations of normal weight. CONCLUSION: It is probable that there is a synergistic effect for obesity, where the presence of oxidative stress and single nucleotide polymorphisms (SNP) of leptin and its receptor contributes to the generation of pathological subcutaneous fat of obesity, together with the environmental conditions of the populations.

All-trans retinoic acid improves pancreatic cell proliferation on induced type 1 diabetic rats.

All-trans retinoic acid (ATRA) has been extensively studied as an integrating component of endocrine functions in the pancreas. The aim of this study was to evaluate the effects of ATRA on physiopathological biomarkers in an experimental model of rat with type 1 diabetes induced by alloxan (T1D). Twenty Wistar rats were divided equally into five groups, each receiving a different treatment: a control group (CG), a diabetic group without T1D treatment, a diabetic group treated with ATRA, a diabetic group supplemented with vitamin E (VIT E), and a group that was given olive oil (V). The administration of ATRA for 17 days produced a significant reduction in weight and glucose levels, compared to the T1D and VIT E groups. The evaluation of total antioxidant capacity (TAC) and lipoperoxidation showed no relevant difference among the groups. The results of the histological analysis showed similarities both in the size and in the number of islets of Langerhans in the pancreatic tissue obtained from the ATRA group and the CG. ATRA displayed a significant reduction of glycemic values in diabetic rats. Ultrastructurally, ß-cells, acinar, and ductal cells restored their normal appearance. ATRA can contribute to the recovery of pancreatic damage due to alloxan induction. It seems that the antioxidant effect of ATRA is not responsible for the differences observed.

Eryptosis and oxidative damage in hypertensive and dyslipidemic patients.

Arterial hypertension is a disease that often coexists with dyslipidemia. Both disorders can produce oxidative stress. Studies in vivo and in vitro have proven that oxidative stress can induce an increment of the erythrocyte apoptosis (eryptosis), through the rise of free intracellular calcium concentration ([Ca2+]i). Higher levels of eryptosis have not been described in patients with hypertension, dyslipidemia, or both combined. This study involved 81 men between 26 and 50 years old, assorted into four groups: normotensive with and without dyslipidemia, and hypertensive with and without dyslipidemia. Hypertensive and/or dyslipidemic patients had double mean lipid peroxidation and 30% less mean GSH concentration than the normotensive non-dyslipidemic patients. Mean [Ca2+]i in hypertensive patients was 100 and 200% higher, in patients without and with dyslipidemia, respectively, compared to normotensive patients. Dyslipidemic normotensive patients had three times higher mean PS externalization than the normotensive non-dyslipidemic patients, and the hypertension condition doubled this difference. Hypertensive patients had higher eryptosis associated with higher levels of [Ca2+]i and oxidative stress, suggesting that eryptosis participates in the pathophysiological mechanisms of hypertension. The quantitative analysis, when the dyslipidemic factor is included, shows that oxidative stress-[Ca2+]i-eryptosis do not follow a unique pattern in the different groups and suggests the existence of mechanisms of induction and molecular pathways alternative or additional to oxidative stress and [Ca2+]i, respectively.

Vitamin E Deficiency and Oxidative Status are Associated with Prediabetes in Apparently Healthy Subjects.

BACKGROUND: Previous studies have indicated that vitamin E deficiency and oxidative stress affect the beta cell function. Hence, the aim of this study was to determine the association between vitamin E deficiency and oxidative status with prediabetes in apparently healthy subjects. METHODS: Apparently healthy men and women aged 18-65 years were enrolled in a case-control study. Individuals with new diagnosis of prediabetes were considered as cases and compared with a control group of individuals with normal glucose tolerance. Smoking, alcohol intake, pregnancy, diabetes, kidney disease, liver disease, cardiovascular disease, malignancy, glucocorticoid treatment and consumption of lipid-lowering drugs, antioxidants and vitamin supplements were exclusion criteria. Vitamin E deficiency was defined by serum levels of α-tocopherol <11.6 µmol/L, oxidative status was assessed by total antioxidant capacity and lipid peroxidation, and prediabetes was considered by the presence of impaired fasting glucose and/or impaired glucose tolerance. RESULTS: A total of 148 subjects were allocated into the case (n = 74) and control (n = 74) groups. The frequency of vitamin E deficiency was higher in the case group (41.8%) compared with the control group (35.1%), p = 0.03. The logistic regression analysis adjusted by age, waist circumference and body mass index, revealed a significant association between vitamin E deficiency (OR 3.23; 95% CI: 1.34-7.79, p = 0.009), lipoperoxidation (OR 2.82; CI 95%: 1.42-5.59, p = 0.003) and total antioxidant capacity (OR 0.93; CI 95%: 0.90-0.96, p <0.001) with prediabetes. CONCLUSIONS: Results of the present study suggest that both vitamin E deficiency and oxidative status are associated with prediabetes in apparently healthy subjects.

[Relation of leptin in plasma with oxidative damage in indigenous tepehuán and mestizo populations from Durango]. / Relación de la leptina en plasma con el daño oxidativo en poblaciones indígena tepehuana y mestiza de Durango.

BACKGROUND: Obesity is a multifactorial metabolic disorder that involves lipid peroxidation (LPX), activating the antioxidant systems to counteract cellular damage. Objective: To evaluate the correlation between the antioxidant capacity and LPX levels of /eptin, in indigenous Tepehuan and Mestizo populations of the State of Durango. METHODS: We conducted a nutritional clinical study and lipid profile to confirm the state of health of a group of 60 indigenous Tepehuan of Mezquital and 68 mestizos subjects of Durango city, aged between 18 to 59 years. We determined the concentrations of leptin, antioxidant capacity and LPX in fasting conditions on plasma of participants, comparing averages, minimum, maximum, and standard deviation through ANOVA and Kruskai-Wal/is. For the correlation of variables, Pearson test was applied, getting the r value. RESULTS: Leptin levels were lower in indigenous Tepehuan than mestizos independent of body mass index. Mestizo subjects and Tepehuan with overweight and obesity (OW/0) or both ethnic groups show a greater degree of LPX (3.39 ± 0.31, 2.72 ± 0.54 MDA J.lmol/1, respectively; p < 0.05); however, OW/0 mestizos show more activation of its (0.37±0. 03 meqltrolox) than Tepehuan normal weight (NW) and OW/0 (0.32 ±0. 01 meq/trolox). The correlation between antioxidant capacity and LPX in mixed OW/0 was positive (r = 0.9; p < 0. 001). There is a correlation between levels of leptin and the antioxidant capacity of Tepehuan subjects both NW and OW/0 (r = 0.40; p < 0.05 and r = -0.66; p < 0.0001, respectively). CONCLUSION: Tepehuan groups with OW/0 have less oxidative damage, while antioxidant mechanisms have a smaller activation than the top crosses of the same nutritional condition. The results suggest that antioxidant capacity has an implication on the regulation of leptin levels in Tepehuan subjects.

Eryptosis in lead-exposed workers.

Eryptosis is a physiological phenomenon in which old and damaged erythrocytes are removed from circulation. Erythrocytes incubated with lead have exhibited major eryptosis. In the present work we found evidence of high levels of eryptosis in lead exposed workers possibly via oxidation. Blood samples were taken from 40 male workers exposed to lead (mean blood lead concentration 64.8µg/dl) and non-exposed workers (4.2µg/dl). The exposure to lead produced an intoxication characterized by 88.3% less δ-aminolevulinic acid dehydratase (δALAD) activity in lead exposed workers with respect to non-lead exposed workers. An increment of oxidation in lead exposed workers was characterized by 2.4 times higher thiobarbituric acid-reactive substance (TBARS) concentration and 32.8% lower reduced/oxidized glutathione (GSH/GSSG) ratio. Oxidative stress in erythrocytes of lead exposed workers is expressed in 192% higher free calcium concentration [Ca(2+)]i and 1.6 times higher µ-calpain activity with respect to non-lead exposed workers. The adenosine triphosphate (ATP) concentration was not significantly different between the two worker groups. No externalization of phosphatidylserine (PS) was found in non-lead exposed workers (<0.1%), but lead exposed workers showed 2.82% externalization. Lead intoxication induces eryptosis possibly through a molecular pathway that includes oxidation, depletion of reduced glutathione (GSH), increment of [Ca(2+)], µ-calpain activation and externalization of PS in erythrocytes. Identifying molecular signals that induce eryptosis in lead intoxication is necessary to understand its physiopathology and chronic complications.

CTCF and CTCFL mRNA expression in 17ß-estradiol-treated MCF7 cells.

Estrogens play a key role in breast cancer, with 60-70% of the cases expressing estrogen receptors (ERs), which are encoded by the ESR1 gene. CTCFL, a paralogue of the chromatin organizer CTCF, is a potential biomarker of breast cancer, but its expression in this disease is currently controversial. A positive correlation has been reported between CTCFL and ERs in breast tumors and there also exists a coordinated interaction between CTCF and ERs in breast cancer cells. Therefore, there appears to be an association between CTCF, CTCFL and estrogens in breast cancer; however, there has been no report on the effects of estrogens on CTCF and CTCFL expression. The aim of this study was to determine the effect of 17ß-estradiol (E2) on the CTCF and CTCFL mRNA expression in the MCF7 breast cancer cell line. The promoter methylation status of CTCFL and data mining for estrogen response elements in promoters of the CTCF and CTCFL genes were also determined. The transcription of CTCF and CTCFL was performed by quantitative polymerase chain reaction (qPCR) and the promoter methylation status of CTCFL was determined by methylation-specific PCR. The MCF7 cells exhibited basal transcription of CTCF, which was significantly downregulated to 0.68 by 1 µM E2; basal or E2-regulated transcription of CTCFL was not detected. Under basal conditions, the CTCFL promoter was methylated. Through data mining, an estrogen response element was identified in the CTCF promoter, but no such element was found in CTCFL. These results suggested that estrogens may modulate CTCF expression, although there was no apparent association between ERs and CTCFL.

Effect of vitamin E and C supplementation on oxidative damage and total antioxidant capacity in lead-exposed workers.

The molecular response of the antioxidant system and the effects of antioxidant supplementation against oxidative insult in lead-exposed workers has not been sufficiently studied. In this work, antioxidants (vitamin E 400 IU+vitamin C 1g/daily) were supplemented for one year to 15 workers exposed to lead (73 µg of lead/dl of blood) and the results were compared with those on 19 non-lead exposed workers (6.7 µg of lead/dl). Lead intoxication was accompanied by a high oxidative damage and an increment in the erythrocyte antioxidant response due to increased activity of catalase and superoxide dismutase. Antioxidant supplementations decreased significantly the oxidative damage as well as the total antioxidant capacity induced by lead intoxication with reduction of the antioxidant enzyme activities. We conclude that antioxidant supplementation is effective in reducing oxidative damage and induces modifications in the physiopathological status of the antioxidant response in lead-exposed workers.