Arsenic: A Perspective on Its Effect on Pioglitazone Bioavailability

María Cruz del Rocío Terrones-Gurrola, Patricia Ponce-Peña, José Manuel Salas-Pacheco, Abelardo Camacho-Luis, Amaury de Jesús Pozos-Guillén, Guillermo Nieto-Delgado, Olga Dania López-Guzmán and Angel Antonio Vértiz-Hernández ()
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María Cruz del Rocío Terrones-Gurrola: Coordinación Académica Región Altiplano, Universidad Autónoma de San Luis Potosí, Matehuala 78700, Mexico
Patricia Ponce-Peña: Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Durango 34120, Mexico
José Manuel Salas-Pacheco: Instituto de Investigaciones Científicas, Universidad Juárez del Estado de Durang, Durango 34000, Mexico
Abelardo Camacho-Luis: Centro de Investigación en Alimentos y Nutrición, Facultad de Medicina y Nutrición, Universidad Juárez del Estado de Durang, Durango 34000, Mexico
Amaury de Jesús Pozos-Guillén: Facultad de Estomatología, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78290, Mexico
Guillermo Nieto-Delgado: Departamento de Físico-Matemáticas, Universidad Autónoma de San Luis Potosí, San Luis Potosí 78290, Mexico
Olga Dania López-Guzmán: Facultad de Ciencias Químicas, Universidad Juárez del Estado de Durango, Durango 34120, Mexico
Angel Antonio Vértiz-Hernández: Coordinación Académica Región Altiplano, Universidad Autónoma de San Luis Potosí, Matehuala 78700, Mexico

IJERPH, 2023, vol. 20, issue 3, 1-12

Abstract: 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.

Keywords: pioglitazone; CYP 450; arsenic; iron; metabolism (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
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