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.