Cyclosporine A inhibition of microcystin toxins.
Cyclosporine A (CyA) given i.v. at a dose of 1.25 mg/mouse blocks a subsequent i.v. lethal dose (1.7-1.8 x LD50) of microcystin-LR for 24 hr, and is about 50% protective at 48 hr. Conversely, the fraction of mice that can be rescued by CyA (0.2 mg/mouse) after a lethal dose of microcystin-LR decreases rapidly with a pharmacodynamic half-time of only about 100 sec. The prophylactic action of CyA was tested against lethal doses of four microcystins. The acute lethality of 1.7-1.8 x LD50 dose of microcystin-LR, -RR, -LY, or -LA given 1 hr after administration of 0.2 mg of CyA is 0%, 0%, 58%, or 100%, respectively. Even a 0.6 mg/mouse dose of CyA is ineffective prophylaxis against a lethal dose of microcystin-LA. The inhibitory potency of CyA on microcystin toxicity can be completely reversed by the single L-amino acid substitution of alanine for arginine in the microcystin.
Stoner
R D
RD
Medical Department, Brookhaven National Laboratory, Upton, NY 11973.
Adams
W H
WH
Slatkin
D N
DN
Siegelman
H W
HW
D000818:Animals; D003524:Cyclosporins / Q000494:pharmacology*; D003643:Death; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008387:Marine Toxins; D051379:Mice; D008815:Mice, Inbred Strains; D052998:Microcystins; D010456:Peptides, Cyclic / Q000037:antagonists & inhibitors; D013997:Time Factors
D003524:Cyclosporins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C049865:cyanoginosin-LA; C063855:microcystin RR; C057862:cyanoginosin LR