Chronic Exposure to Arsenic and Fluoride Starting at Gestation Alters Liver Mitochondrial Protein Expression and Induces Early Onset of Liver Fibrosis in Male Mouse Offspring.

Autor: González-Alfonso WL; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, México., Petrosyan P; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, México., Del Razo LM; Departamento de Toxicología, Centro de Investigación y Estudios Avanzados, 07360, Mexico City, Mexico., Sánchez-Peña LC; Departamento de Toxicología, Centro de Investigación y Estudios Avanzados, 07360, Mexico City, Mexico., Tapia-Rodríguez M; Unidad de Microscopia, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, 04510, Mexico City, Mexico., Hernández-Muñoz R; Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, 04510, México., Gonsebatt ME; Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City, 04510, México. margen@unam.mx.
Jazyk: angličtina
Zdroj: Biological trace element research [Biol Trace Elem Res] 2024 Apr 27. Date of Electronic Publication: 2024 Apr 27.
DOI: 10.1007/s12011-024-04198-1
Abstrakt: The presence of arsenic (As) and fluoride (F - ) in drinking water is of concern due to the enormous number of individuals exposed to this condition worldwide. Studies in cultured cells and animal models have shown that As- or F-induced hepatotoxicity is primarily associated with redox disturbance and altered mitochondrial homeostasis. To explore the hepatotoxic effects of chronic combined exposure to As and F - in drinking water, pregnant CD-1 mice were exposed to 2 mg/L As (sodium arsenite) and/or 25 mg/L F - (sodium fluoride). The male offspring continued the exposure treatment up to 30 (P30) or 90 (P90) postnatal days. GSH levels, cysteine synthesis enzyme activities, and cysteine transporter levels were investigated in liver homogenates, as well as the expression of biomarkers of ferroptosis and mitochondrial biogenesis-related proteins. Serum transaminase levels and Hematoxylin-Eosin and Masson trichrome-stained liver tissue slices were examined. Combined exposure at P30 significantly reduced GSH levels and the mitochondrial transcription factor A (TFAM) expression while increasing lipid peroxidation, free Fe 2+ , p53 expression, and serum ALT activity. At P90, the upregulation of cysteine uptake and synthesis was associated with a recovery of GSH levels. Nevertheless, the downregulation of TFAM continued and was now associated with a downstream inhibition of the expression of MT-CO2 and reduced levels of mtDNA and fibrotic liver damage. Our experimental approach using human-relevant doses gives evidence of the increased risk for early liver damage associated with elevated levels of As and F - in the diet during intrauterine and postnatal period.
(© 2024. The Author(s).)
Databáze: MEDLINE
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