Neurotoxicity of hexachlorophene in mice: implications of altered cerebral amino acid profiles.

Abstract

Oral administration of hexachlorophene (HCP) produced neurotoxic symptoms in mice. Using high-pressure liquid chromatography, the profiles of the cerebral free amino acids of the control and HCP intoxicated mice were analyzed. There was a significant rise in the levels of the neutral amino acids glutamine, threonine, phenylalanine, leucine, isoleucine and valine. A rise in glutamine levels was most notable, and was associated with increased glutamine synthetase and decreased glutaminase activity levels. Concentrations of the acidic amino acids, aspartic acid and glutamic acid were significantly decreased. The γ-aminobutyric acid (GABA) levels were increased, while glutamic acid-to-glutamine and glutamic acid + aspartic acid-to-GABA ratios showed significant decrements in the brains of mice subjected to repeated HCP administration. The characteristic changes, particularly of transmitter amino acids, denoted a trend towards the depletion of excitatory amino acids and an accumulation of the inhibitory amino acid GABA, which might deserve consideration in the expression of neurologic symptoms in HCP intoxication.