ROS and ERK Pathway Mechanistic Approach on Hepatic Insulin Resistance After Chronic Oral Exposure to Cadmium NOAEL Dose.

Autor: Sarmiento-Ortega VE; Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, Chemistry Department, Meritorious Autonomous University of Puebla, 14 South, FCQ1, Ciudad Universitaria, C.P. 72560, Puebla, Mexico., Moroni-González D; Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, Chemistry Department, Meritorious Autonomous University of Puebla, 14 South, FCQ1, Ciudad Universitaria, C.P. 72560, Puebla, Mexico., Diaz A; Department of Pharmacy, Faculty of Chemistry Science, Meritorious Autonomous University of Puebla, 22 South, FCQ9, Ciudad Universitaria, C.P. 72560, Puebla, Mexico., Brambila E; Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, Chemistry Department, Meritorious Autonomous University of Puebla, 14 South, FCQ1, Ciudad Universitaria, C.P. 72560, Puebla, Mexico., Treviño S; Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, Chemistry Department, Meritorious Autonomous University of Puebla, 14 South, FCQ1, Ciudad Universitaria, C.P. 72560, Puebla, Mexico. samuel.trevino@correo.buap.mx.
Jazyk: angličtina
Zdroj: Biological trace element research [Biol Trace Elem Res] 2023 Aug; Vol. 201 (8), pp. 3903-3918. Date of Electronic Publication: 2022 Nov 08.
DOI: 10.1007/s12011-022-03471-5
Abstrakt: Cadmium is a critical toxic agent in occupational and non-occupational settings and acute and chronic environmental exposure situations that have recently been associated with metabolic disease development. Until now, the no observed adverse effect level (NOAEL) of cadmium has not been studied regarding insulin resistance development. Therefore, we aimed to monitor whether chronic oral exposure to cadmium NOAEL dose induces insulin resistance in Wistar rats and investigate if oxidative stress and/or inflammation are related. Male Wistar rats were separated into control (standard normocalorie diet + water free of cadmium) and cadmium groups (standard normocalorie diet + drinking water with 15 ppm CdCl 2 ). At 15, 30, and 60 days, oral glucose tolerance, insulin response, and insulin resistance were analyzed using mathematical models. In the liver glycogen, triglyceride, pro- and anti-inflammatory cytokines, cadmium, zinc, metallothioneins, and redox balance were quantified. Immunoreactivity analysis of proteins involved in metabolic and mitogenic insulin signaling was performed. The results showed that a cadmium NOAEL dose after 15 days of exposure causes ROS and mitogenic arm of insulin signaling to increase while hepatic glycogen diminishes. At 30 days, Cd accumulation accentuated ROS production, hepatic triglyceride overaccumulation, and mitogenic signals that develop insulin resistance. Finally, inflammation and lipid peroxidation appear after 60 days of Cd exposure, while lipids and carbohydrate homeostasis deteriorate. In conclusion, environmental exposure to cadmium NAOEL dose causes hepatic Cd accumulation and ROS overproduction that chronically declines the antioxidant defense, deteriorates metabolic homeostasis associated with the mitogenic pathway of insulin signaling, and induces insulin resistance.
(© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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