Cyclosporin A--a chemoprotectant against microcystin-LR toxicity.
Microcystin-LR (MCLR) is a potent hepatotoxin that rapidly produces death in experimental animals. We have shown that cyclosporin A (CsA) can prevent the toxic and lethal effects of MCLR in mice. The LD50 of MCLR in mice is approximately 61 micrograms/kg, and 100 micrograms/kg produces death in 100% of treated mice. The minimum dose of CsA which prevented lethality in mice given 100 micrograms MCLR/kg i.p. was 10 mg/kg. This dose of CsA did not protect mice against higher doses of MCLR. Survival of all mice given 100 micrograms MCLR/kg was achieved if 10 mg CsA/kg was given 0.5-3 h prior to the MCLR but not if the CsA was co-administered or given after the MCLR. The results indicate that CsA effectively protects mice against a lethal dose of MCLR, but that the time of administration and the dose of CsA are critical determinants of the chemoprotective effects.
Hermansky
S J
SJ
Creighton University Health Sciences Center, Omaha, NE 68178.
Casey
P J
PJ
Stohs
S J
SJ
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003524:Cyclosporins / Q000627:therapeutic use*; D005260:Female; D007274:Injections, Intraperitoneal; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007928:Lethal Dose 50; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors* / Q000633:toxicity
D003524:Cyclosporins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; C057862:cyanoginosin LR