Dose dependent effect of ricin on DNA damage and antioxidant enzymes in mice.
Ricin a glycoprotein from the Ricinus communis seeds, is known to have diverse toxic effects on cells of different visceral organs. We have studied the effect of ricin (0.5, 1.0 and 2.0 LD50) on various oxidative stress markers at 1, 3 and 7 day post exposure following i.p. administration in Swiss albino male mice. Results of this study revealed that ricin induces generation of reactive species, lipidperoxidation, DNA fragmentation and depletion of GSH. Activity of antioxidant cascade related enzyme like superoxide dismutase (SOD), glutathione peroxidase (GPx) decreased, while glutathione reductase (GR) and catalase activity increased. Superoxide dismutase and glutathione peroxidase activity was decreased significantly in liver, spleen and kidney. The decrease was more prominent on 7 day of post exposure in all the exposed doses. A significant increase in the activities of catalase was observed in plasma, liver, spleen and kidney on 7 day following ricin exposure. Glutathione reductase increased significantly as early as 24 h following 1.0 LD50 dose. Lipid peroxidation increased and non protein sulfhydryl content decreased in all the tissues at different time intervals. Total antioxidant status was reduced as early as 1 day post exposure. Nearly two fold increase was observed in DNA fragmentation following 0.5 LD50 dose of ricin on 1 day post exposure. DNA diffusion assay also indicated an early damage to DNA due to ROS. An early change in DNA fragmentation, DNA diffusion, and total antioxidant status and in the activity of various enzymes indicates that ricin produce oxidative stress by generation of reactive oxygen species as early as 24 h at a minimum dose of 0.5 LD50. Probably this is the first study which indicate that ricin induced oxidative stress at a minimum dose of 0.5 LD50.
Kumar
O
O
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Gwalior, India. omkumar63@rediffmail.com
Lakshmana Rao
P V
PV
Pradhan
S
S
Jayaraj
R
R
Bhaskar
A S B
AS
Nashikkar
A B
AB
Vijayaraghavan
R
R
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012276:Ricin / Q000494:pharmacology*; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D012276:Ricin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase