Effects of 1,3,5-Trinitrobenzene on cytotoxicity and metabolic activity of type I astrocytes of rats.
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.
Department of Pathology, College of Veterinary Medicine, Oklahoma State University, Stillwater, Oklahoma, USA.
Eric L
EL
Stair
Gunda
G
Reddy
Jerry W
JW
Ritchey
Jeremiah T
JT
Saliki
Charles W
CW
Quails
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology* / Q000473:pathology; D018929:Cell Culture Techniques / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000166:cytology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010100:Oxygen; D051381:Rats; D011916:Rats, Inbred F344; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014301:Trinitrobenzenes / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D003470:Culture Media; D013778:Tetrazolium Salts; D013844:Thiazoles; D014301:Trinitrobenzenes; D014874:Water Pollutants, Chemical; C070380:3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium; C029222:sym-trinitrobenzene; D007770:L-Lactate Dehydrogenase; D010100:Oxygen