Arsenic: A Perspective on Its Effect on Pioglitazone Bioavailability.

Arsenic (As) is a common contaminant in drinking water in northeastern Mexico, which reduces the expression of cytochrome P450 (CYP 450). This enzyme group metabolizes numerous drugs, such as oral antidiabetic drugs such as pioglitazone (61% CYP 3A4, 49% CYP 2C8). When CYP 450's function is inadequate, it has decreased therapeutic activity in type 2 diabetes mellitus (T2DM). This study aimed to establish the effect of As on pioglitazone metabolism in patients with T2DM. METHODOLOGY: Urine, water, and plasma samples from a healthy population (n = 11) and a population with T2DM (n = 20) were obtained. Samples were analyzed by fluorescence spectroscopy/hydride generation (As) and HPLC (pioglitazone). Additionally, CYP 3A4 and CYP 2C8 were studied by density functional theory (DFT). RESULTS: The healthy and T2DM groups were exposed via drinking water to >0.010 ppm, Ka values with a factor of 4.7 higher, Cl 1.42 lower, and ABCt 1.26 times higher concerning the healthy group. In silico analysis (DFT) of CYP 3A4 and CYP 2C8 isoforms showed the substitution of the iron atom by As in the active sites of the enzymes. CONCLUSIONS: The results indicate that the substitution of Fe for As modifies the enzymatic function of CYP 3A4 and CYP 2C8 isoforms, altering the metabolic process of CYP 2D6 and CYP 3A4 in patients with T2DM. Consequently, the variation in metabolism alters the bioavailability of pioglitazone and the expected final effect.

Apoptosis in pancreatic ß-cells is induced by arsenic and atorvastatin in Wistar rats with diabetes mellitus type 2.

INTRODUCTION: Diabetes Mellitus type 2 (T2D) is a multifactorial disease. However, it is known that there is an important effect in pancreatic ß-cells caused by apoptosis of pro-apoptotic proteins, possibly related to arsenic exposure and atorvastatin treatment. OBJECTIVE: The goal of this study was to evaluate the effects of atorvastatin treatment on apoptosis of pancreatic ß-cells in Wistar rats with induced diabetes type 2 exposed to arsenic. MATERIAL & METHODS: T2D in Wistar rats was induced by administration of Streptozotocin. The plasmatic glucose concentrations were measured using the glucose oxidase method, and the concentration of glycated hemoglobin (HbA1c) in whole blood was determined. Exposure to arsenic was measured from urine using atomic absorption with hydride generation, and pro-apoptotic proteins in pancreatic ß-cells were observed using the Western blotting technique. RESULTS: Caspase-3 was present in rats that were treated with 10 mg/kg of oral atorvastatin and exposed to 0.01 and 0.025 mg/L of arsenic, but no others proteins were present, such as pro Caspase-8, bcl-2, and Fas. The glycemic levels were 129.2 ±â€¯7.0 mg/dL in the control group and 161.8 ±â€¯14.6 mg/dL and 198.3 ±â€¯18.2 mg/dL (p < .05) in the study groups. HbA1c increased from 2.53% to 3.64% (p < .05) in the control and study groups. CONCLUSIONS: Atorvastatin treatment and arsenic exposure alone are capable of generating apoptosis in pancreatic ß-cells of Wistar rats with T2D. Together, all of these factors induce apoptosis in pancreatic cells.

Association between urine fluoride and dental fluorosis as a toxicity factor in a rural community in the state of San Luis Potosi.

OBJECTIVE: The aim of this study is to investigate urine fluoride concentration as a toxicity factor in a rural community in the state of San Luis Potosi, Mexico. MATERIALS AND METHODS: A sample of 111 children exposed to high concentrations of fluoride in drinking water (4.13 mg/L) was evaluated. Fluoride exposure was determined by measuring urine fluoride concentration using the potentiometric method with an ion selective electrode. The diagnosis of dental fluorosis was performed by clinical examination, and the severity of damage was determined using Dean's index and the Thylstrup-Fejerskov (TF) index. RESULTS: The range of exposure in the study population, evaluated through the fluoride content in urine, was 1.1 to 5.9 mg/L, with a mean of 3.14±1.09 mg/L. Dental fluorosis was present in all subjects, of which 95% had severe cases. Higher urine fluoride levels and greater degrees of severity occurred in older children. CONCLUSIONS: The results show that dental fluorosis was determined by the presence of fluoride exposure finding a high positive correlation between the severity of fluorosis and urine fluoride concentration and the years of exposure suggested a cumulative effect.