Distribution of glutathione and technetium-99m-meso-HMPAO in normal and diethyl maleate-treated mouse brain mitochondria.

Abstract

The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed. We studied subcellular distribution of 99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice. In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the uptake of 99mTc-meso-HMPAO and GSH content in mitochondrial, cytosolic and nuclear fractions, with a correlation coefficient (r) of 0.814, 0.834 and 0.784, respectively. Mitochondria are a major subcellular fraction for the uptake of 99mTc-meso-HMPAO by the brain, and GSH in mitochondria contributes to the accumulation of 99mTc-meso-HMPAO.