Oxidative damage and gene expression profile of antioxidant enzymes after T-2 toxin exposure in mice.
T-2 toxin is one of the most potent trichothecenes, and on exposure causes severe human and animal diseases. We investigated the dose- and time-dependent effect of T-2 toxin on certain biochemical variables, oxidative damage in terms of antioxidant enzyme activity, and gene expression profile in mice. Mice treated intraperitoneally with either 1 LD50 or 2 LD50 dose (5.61 and 11.22 mg/kg body weight, respectively) of T-2 toxin showed significant alterations in hepatic alanine amino transferase, aspartate amino transferase, and lactate dehydrogenase. Significant changes in hepatic lipid peroxidation, depletion of glutathione (GSH), and expression of heat shock protein-70 indicated oxidative damage. We also evaluated the activity of antioxidant enzymes and compared the gene expression profile by quantitative real-time reverse transcriptase-polymerase chain reaction. Except for glutathione reductase (GR), there was a significant increase in activity of glutathione-S-transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase at 1 LD50 dose. At 2 LD50 dose, SOD showed decrease in activity, whereas GST, GPx, and catalase showed significant increase. In contrast, gene expression profile showed downregulation in GR, GPx, GST, and catalase at 1 LD50 dose. At 2 LD50 dose except GSH synthetase, all other genes were downregulated. The results clearly show oxidative stress as one of the mechanisms of T-2 toxin-mediated toxicity.
Chaudhari
Manjari
M
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior 474002, Madhya Pradesh, India.
Jayaraj
R
R
Santhosh
S R
SR
Rao
P V Lakshmana
PV
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000096:biosynthesis*; D013605:T-2 Toxin / Q000633:toxicity*
D000975:Antioxidants; D010088:Oxidoreductases; D013605:T-2 Toxin