Brain oxidative stress after dermal and subcutaneous exposure of T-2 toxin in mice.
T-2 toxin belongs to group of mycotoxins and is found as a natural contaminant in cereals, feed and vegetables. In the present study we evaluated acute toxicity of dermal and subcutaneous exposure of T-2 toxin on brain oxidative stress in mice. Mice were exposed to 1 LD50 of T-2 toxin either by dermal (5.94 mg/kg) or subcutaneous (1.54 mg/kg body weight) route and sacrificed at 1, 3 and 7 days post-exposure. T-2 toxin treated animals showed time dependent increase in reactive oxygen species generation, glutathione depletion, lipid peroxidation and protein carbonyl content in brain in both the routes of exposure. Gene expression profile of antioxidant enzymes showed significant increase in superoxide dismutase and catalase in percutaneous route and glutathione reductase and glutathione peroxidase in subcutaneous route. Immunoblot analysis of antioxidant enzymes correlated with gene expression profile. T-2 toxin exposure resulted in down regulation of transcription factor Nrf2 and its downstream target genes of phase II detoxifying enzymes NQO1, Gclc, Gclm and hemeoxygenase-1. Results of our study show that percutaneously and subcutaneously applied T-2 toxin can cause brain oxidative damage possibly after crossing blood-brain barrier by altering its permeability.
Chaudhary
Manjari
M
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India.
Rao
P V Lakshmana
PV
D000287:Administration, Topical; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D009419:Nerve Tissue Proteins / Q000187:drug effects; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D050050:Protein Carbonylation / Q000187:drug effects; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013605:T-2 Toxin / Q000008:administration & dosage / Q000633:toxicity*
D000975:Antioxidants; D009419:Nerve Tissue Proteins; D012313:RNA; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D013605:T-2 Toxin