1,3,5-trinitrobenzene-induced encephalopathy in male Fischer-344 rats.

摘要

Scope and method of study. The purpose of this study was to examine the neurotoxic effects of 1,3,5-trinitrobenzene (TNB) in male Fischer-344 rats. Concern over release of this chemical into the environment has resulted in studies to illuminate possible mammalian risks from exposure. Initial studies involved dosing male Fischer-344 rats with L-Arginine, NG-Nitro-L-arginine methyl ester, pyrithiamine, and thiamine prior to and during TNB administration. The second study involved dosing male Fischer-344 rats with antioxidants (vitamin E, vitamin C, and N-acetylcysteine) in an attempt to prevent or decrease the neurotoxic lesions associated with TNB. Cell cultures of Fischer-344 rat astrocytes as well as human and bovine endothelial cells in culture were exposed to TNB to determine a toxic dose in vitro and attempt to identify early preneuropathic indices of toxicity.; Findings and conclusions. L-Arginine, NG-Nitro-L-arginine methyl ester, pyrithiamine, and thiamine did not produce significant changes in the TNB-induced encephalopathy at the dosage levels that were administered in this study. Vitamin E, vitamin C and N-acetylcysteine were also non-protective at their respective dosage levels when co-administered with TNB. Studies with TNB on rat astrocytes, bovine corneal and human umbilical endothelial cells in culture displayed increased toxicity as determined by LDH release and metabolic activity. The results presented in this study do not lend strong support to the hypothesis that endogenous nitric oxide and thiamine play a role in TNB-induced encephalopathy. However, the data obtained from in vitro studies with astrocytes and endothelial cells do support the contention that TNB-induced neurotoxicosis could be partially mediated by its potential toxic effects on the blood-brain barrier.