The effect of cyclosporine A on survival time in salicylate-poisoned rats.
Salicylate (SAL) produces mitochondrial membrane permeability transition (MPT) with resultant oxidative phosphorylation uncoupling. Cyclosporine A (CSA) inhibits SAL-induced MPT. This study determined if CSA pretreatment prolonged survival time in SAL-poisoned rats. Twenty-nine rats were randomized to receive pre-treatment with either 30 mg/kg CSA or equal volume of control diluent intraperitoneally (i.p.). Four hours later, all rats received 1700 mg/kg sodium salicylate i.p. Survival time, whole blood CSA ([CSA]), and serum sodium ([Na]), glucose and SAL ([SAL]) concentrations were determined. The results showed median survival time for controls was 18 min (95% CI 14-22 min) and for CSA animals was 14 min (95% CI 13-15 min). Univariate and multivariate analyses and Cox proportional hazard regression revealed CSA treatment was associated with higher [SAL], which was associated with shortened survival times. The CSA group also demonstrated shorter survival times for a given [SAL]. In conclusion, CSA pre-treatment shortened survival in SAL-poisoned rats.
Department of Medical Toxicology, Good Samaritan Regional Medical Center, Phoenix, Arizona, USA.
Kenneth D
KD
Katz
Steven C
SC
Curry
Daniel E
DE
Brooks
Richard D
RD
Gerkin
D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D008297:Male; D011041:Poisoning / Q000517:prevention & control*; D051381:Rats; D012459:Salicylates / Q000506:poisoning*; D015996:Survival Rate; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D012459:Salicylates; D016572:Cyclosporine