The NOAEL Metformin Dose Is Ineffective against Metabolic Disruption Induced by Chronic Cadmium Exposure in Wistar Rats
Victor Enrique Sarmiento-Ortega,
Eduardo Brambila,
José Ángel Flores-Hernández,
Alfonso Díaz,
Ulises Peña-Rosas,
Diana Moroni-González,
Violeta Aburto-Luna,
Samuel Treviño
Affiliations
Victor Enrique Sarmiento-Ortega
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Eduardo Brambila
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
José Ángel Flores-Hernández
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Alfonso Díaz
Department of Pharmacy, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Ulises Peña-Rosas
Department of Analytic Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Diana Moroni-González
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Violeta Aburto-Luna
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Samuel Treviño
Laboratory of Chemical-Clinical Investigations, Department of Clinical Chemistry, Faculty of Chemistry Science, University Autonomous of Puebla, 14 South. CQ1, University City, Puebla C.P. 72560, Mexico
Previous studies have proposed that cadmium (Cd) is a metabolic disruptor, which is associated with insulin resistance, metabolic syndrome, and diabetes. This metal is not considered by international agencies for the study of metabolic diseases. In this study, we investigate the effect of metformin on Cd-exposed Wistar rats at a lowest-observed-adverse-effect level (LOAEL) dose (32.5 ppm) in drinking water. Metabolic complications in the rats exposed to Cd were dysglycemia, insulin resistance, dyslipidemia, dyslipoproteinemia, and imbalance in triglyceride and glycogen storage in the liver, muscle, heart, kidney, and adipose tissue. Meanwhile, rats treated orally with a No-observable-adverse-effect level (NOAEL) dose of metformin (200 mg/kg/day) showed mild improvement on serum lipids, but not on glucose tolerance; in tissues, glycogen storage was improved, but lipid storage was ineffective. In conclusion, metformin as a first-line pharmacological therapy must take into consideration the origin and duration of metabolic disruption, because in this work the NOAEL dose of metformin (200 mg/kg/day) showed a limited efficiency in the metabolic disruption caused by chronic Cd exposure.
