The modulating effects of tumor necrosis factor alpha antibody on ricin-induced oxidative stress in mice.
Previous studies in our laboratory have shown that the protein toxin ricin induces an oxidative stress in mice, resulting in increased urinary excretion of malondialdehyde (MDA), formaldehyde (FA), and acetone (ACON). Other toxicants have been shown to induce oxidative stress by macrophage activation with subsequent release of reactive oxygen species and tumor necrosis factor alpha (TNF-alpha). Therefore, the ability of TNF-alpha antibody to modulate ricin-induced urinary carbonyl excretion as well as hepatic lipid peroxidation, glutathione depletion, and DNA single-strand breaks was assessed. Ricin-induced urinary MDA, FA, and ACON were reduced significantly in mice receiving antibody (15,000 U/kg) 2 hours before treatment with ricin (5 micrograms/kg). At 48 hours following ricin treatment, MDA, FA, and ACON concentrations in the urine of TNF antibody-treated mice decreased 25.7, 53.2, and 64.5%, respectively, relative to ricin-treated mice receiving no antibody. In addition, anti-TNF-alpha (1500 U/kg) significantly decreased hepatic lipid peroxidation and DNA single-strand breaks, induced by 5 micrograms ricin/kg, by 49.3 and 44.2%, respectively. The results suggest that macrophage activation and subsequent release of TNF-alpha are involved in ricin toxicity.
Muldoon
D F
DF
Department of Pharmacology, Creigton University Health Sciences Center, Omaha, NE.
Bagchi
D
D
Hassoun
E A
EA
Stohs
S J
SJ
D000096:Acetone / Q000652:urine; D000447:Aldehydes / Q000652:urine; D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage / Q000276:immunology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D015227:Lipid Peroxidation / Q000276:immunology; D008055:Lipids / Q000652:urine; D008099:Liver / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000276:immunology*; D012276:Ricin / Q000633:toxicity*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D000447:Aldehydes; D000911:Antibodies, Monoclonal; D008055:Lipids; D014409:Tumor Necrosis Factor-alpha; D000096:Acetone; D012276:Ricin; D005978:Glutathione