Use of Rifampin as an Effective Chemoprotectant and Antidote against Microcystin-LR Toxicity

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Abstract
Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin that is produced by the blue-green algae, Microcystis aeruginosa. This organism forms blooms in freshwater lakes and ponds. Following ingestion of contaminated waters, deaths of wildlife and domestic animals frequently occur. Due to the lack of available methods and drugs for treating cases of poisoning with this toxin, development of an effective antidote to this toxin is needed. We have examined the ability of the semisynthetic antibiotic rifampin to prevent the toxicity of a lethal dose of MCLR in mice. A dose of 25 mg/kg rifampin given intraper-itoneally coadministered with a lethal dose of MCLR (100 μg/kg) or given 30 or 60 min prior to the MCLR prevented deaths in all animals. Seventy-five percent of the mice were protected from lethality when 25 mg/kg rifampin was given 15 min after the administration of MCLR. The coadministration of 17.5 mg/kg rifampin prevented lethality in 50% of the mice treated with MCLR, while 25% of the mice survived when rifampin was administered 15 min after the MCLR. At 10 mg/kg rifampin the time to death following administration of MCLR was extended, but the animals did not survive. The results indicate that rifampin is an effective chemoprotectant and antidote against the toxicity of MCLR in mice which can be successfully administered after exposure to MCLR.