The NOAEL Metformin Dose Is Ineffective against Metabolic Disruption Induced by Chronic Cadmium Exposure in Wistar Rats.

ABSTRACT

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.