Effects of Valproate Monotherapy on the Oxidant-Antioxidant Status in Mexican Epileptic Children: A Longitudinal Study.

Epilepsy is a neurological disorder that can produce brain injury and neuronal death. Several factors such as oxidative stress have been implicated in epileptogenesis. Valproic acid (VPA) is a widely used drug for the treatment of epilepsy, but the mechanisms underlying these benefits are complex and still not fully understood. The objective of this study was to evaluate, for the first time, the effects of VPA on the oxidant-antioxidant status in Mexican epileptic children before and after 6 or 12 months of treatment with VPA by determining the activities of several plasmatic antioxidant enzymes (glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT)) and oxidant marker (malondialdehyde (MDA), hydrogen peroxide (H2O2), 8-hydroxy-2-deoxyguanosine (8-OHdG), and 3-nitrotyrosine (3-NT) levels) profiles. The possible relationships between these markers and some clinicopathological factors were also evaluated. Plasma samples were obtained from the peripheral blood of 16 healthy children and 32 patients diagnosed with epilepsy, and antioxidant/oxidant markers were measured spectrometrically. Significant decreases in all antioxidant enzyme activities, with the exception of GPx, and increases in all oxidant markers in epileptic subjects versus healthy children were observed. Interestingly, all these effects reverted after VPA monotherapy, although the results were different depending on the treatment period (6 or 12 months). These changes were contingent upon brain imaging findings, type of epilepsy, etiology of epilepsy, and the efficacy of 6 months of VPA monotherapy. Significant and positive correlations of GPx and SOD activities and H2O2 and 8-OHdG levels with the age of children at the beginning of treatment were observed. H2O2 levels were also positively correlated with number of seizures before VPA monotherapy. VPA showed significant antioxidant effects decreasing seizure activity, possibly depending on the presence of cerebral structural alterations, treatment time, and age.

Association of CYP8A1 (Prostacyclin I2 synthase) polymorphism rs5602 with breast cancer in Mexican woman.

Breast cancer (BCa) is the most common cancer in Mexican women. Certain risk factors, such as environmental and lifestyle factors have been implicated in BCa initiation and progression. Moreover, genetic factors, such as single nucleotide polymorphisms (SNPs) of the P450 system, have been reported in BCa. In this report, and for the first time in the literature, we analyzed the rs5602 (67730 T > C) polymorphism in the CYP8A1 in patients with BCa and in healthy Mexican women to identify a potential risk between this polymorphism and BCa. Leukocyte cells from 38 control patients and tissue from radical mastectomy surgeries in 64 BCa patients were used for polymorphism analysis using an allelic discrimination assay with TaqMan probes. Links with clinic-pathological characteristics were also analyzed. Statistical analysis was performed using the standard χ(2) or Fisher exact test statistic. All CYP8A1 genotypes were detected in patients with BCa and the controls. Significant differences were observed in the distribution of CYP8A1 genotypes between the patients and controls (P=0.0008) and allele C was significantly associated with BCa risk (OR 2.08, 95% CI 1.166-3.72, P=0.0178). All polymorphism frequencies were in Hardy-Weinberg Equilibrium (HWE) in the controls (P > 0.05). We found that variant 67730 T > C was significantly associated with an increased risk of BCa (P < 0.05). We not observed an association of the TT and TC + CC genotypes with the clinical stage, BIRADS, estrogen receptor (ER) status, progesterone receptor (PR) status, HER2 status, p53 status, CD34 status, metastasis or therapy use. These results indicate that the CYP8A1 rs5602 SNP is a possible risk factor for BCa in Mexican women. This study showed an association between the CYP8A1 polymorphism and BCa risk in a Mexican population.