Effects of 1,3,5-Trinitrobenzene on Cytotoxicity and Metabolic Activity of Type I Astrocytes of Rats

Abstract

1,3,5-Trinitrobenzene (TNB) is a munitions chemical that causes gliovascular lesions in the brain stem of rats similar to those produced by thiamine deficiency and nitroaromatic compounds, including m-dinitrobenzene. To identify neuropathic indices of toxicity, the effects of varying concentrations (0 to 2 mM) of TNB on cytotoxicity and cellular metabolic activity were examined using cultured astrocytes from Fischer-344 rats. The cytotoxicity was assessed by lactate dehydrogenase (LDH) leakage into the culture medium. Astrocyte metabolic activity was assessed by measuring the conversion of a tetrazolium salt to a formazan product. Additionally, the effects of oxidative stress on cellular metabolic activity were determined by varying oxygen tension via alteration of culture media depth. In vitro, the toxic concentration 50% (TC50) of TNB, which induced cell death, was 16 microM following a 24-h exposure. The concentration of TNB that reduced cellular metabolic activity by 50% was 29 microM following a 24-h exposure. Varying the depth of the culture media did not influence the cellular metabolic activity in control or TNB-treated astrocytes. These results support the hypothesis that TNB induced neurotoxicity could partially be mediated via injury to astrocytes, a major component of the blood-brain barrier.

In vitro evaluation of human xenobiotic toxicity: Scientific concepts and the novel integrated discrete multiple cell coculture (IdMOC) technology

“…Besides hepatocytes, primary cells cultured from various organs such as kidney (Dietrich et al, 2001;Li et al, 2006;Lock et al, 2007), nervous system (Stair et al, 2005;Guizzetti et al, 2005), heart (Hasinoff et al, 2007), skeletal muscle (Mazno et al, 2003), vascular endothelium (Harlan et al, 1983;Kim et al, 2007), lung (Li, 1986;Li and Myers, 1988;Bakand et al, 2007;Han et al, 2007;Sayes et al, 2007), and blood/bone marrow cells (Deldar and Stevens, 1993;Rich and Hall, 2005) have also been applied towards the evaluation of xenobiotic toxicity. The various primary cell systems used may be representative of the appropriate in vivo target cells for their respective organs.…”