Ricin-induced hepatic lipid peroxidation, glutathione depletion, and DNA single-strand breaks in mice.
The ability of ricin, the glycoprotein toxin from the castor bean (Ricinus communis), to stimulate oxidative stress was investigated. Following the i.p. administration of 25 micrograms ricin/kg or the vehicle to female CF-1 mice, the effects of ricin on hepatic lipid peroxidation, nonprotein sulfhydryl (reduced glutathione) content and DNA single-strand breaks were determined at 0, 12, 24, 36, 48 and 72 hr post-treatment. Hepatic lipid peroxidation significantly increased 3.4-, 3.8-, and 3.0-fold relative to control values at 24, 36, and 48 hr post-treatment, respectively. Hepatic nonprotein sulfhydryl concentrations decreased significantly to approximately 51%, 61% and 65% of control values, at 24, 36, and 48 hr, respectively. The incidence of hepatic DNA single-strand breaks increased by 2.9-, 2.8-, and 2.4-fold relative to the zero time values at 24, 36, and 48 hr after treatment with ricin, respectively. No significant differences were observed in either lipid peroxidation or nonprotein sulfhydryl concentrations at 12 or 27 hr post-treatment. Decreases in liver and intestinal weight to body weight ratios were observed in ricin-treated animals, while no changes were observed in spleen and kidney weight to body weight ratios. These results indicate that in the liver of mice, ricin induces an oxidative stress which is maximal at approximately 36 hr post-treatment.
Muldoon
D F
DF
Department of Pharmacology, Creighton University Health Sciences Center, Omaha, NE 68178.
Hassoun
E A
EA
Stohs
S J
SJ
D000818:Animals; D004249:DNA Damage; D004277:DNA, Single-Stranded / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000172:deficiency*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D010084:Oxidation-Reduction; D012276:Ricin / Q000494:pharmacology*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D004277:DNA, Single-Stranded; D013438:Sulfhydryl Compounds; D012276:Ricin; D005978:Glutathione