Determination of Glutathione Levels and Turnover Rates in the Brain and Liver of Mice Treated with Cadmium

Abstract

Cadmium is a toxic metal that affects many organ systems in the body. Medetomidine is an alpha-2 adrenoceptor agonist reported to reduce glutathione (GSH) levels in tissues. We used the effect of medetomidine to determine GSH levels and turnover rates in the brain and liver of mice acutely treated with cadmium. Female mice were treated with either saline (control) or cadmium chloride at 2 mg cadmium/5 ml saline/kg of body weight, itraperitoneally (ip), followed one hour later with medetomidine at 0.2 mg/kg of body weight, ip. Five hours after the medetomidine administration, the mice were sacrificed using terminal ether anesthesia to obtain the whole brain and liver. GSH level was determined in the homogenized brain or liver spectrophotometrically. Turnover parameters (efflux rate constant-k, turnover time, and turnover rate) of GSH were estimated by a steady state kinetic relationship. The levels of GSH after medetomidine or cadmium + medetomidine treatments were reduced in the brain (12.4% and 11.4%, respectively) and liver (3.8% and 15.1%, respectively) of mice in comparison with respective control values. Cadmium reduced GSH trunover rate in the brain of mice by 8% with a corresponding decrease in k value by 8% and an increase of 9% in the turnover time. In the liver, it increased the turnover rate by 320% with a corresponding increase in k value by 319% and a reduction of turnover time by 76%. In conclusion, cadmium differentially affected GSH levels and turnover rates in the brain and liver of mice. Medetomidine administration was found to be a potential simple tool to determine GSH turnover and related parameters in tissues.

Keywords

• alpha-2 agonist
• cadmium
• glutathione
• medetomidine
• turnover rate