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 RESEARCH PAPER
Year : 2004  |  Volume : 36  |  Issue : 2  |  Page : 87-92

Screening of certain chemoprotectants against cyclic peptide toxin microcystin-LR


Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior - 474002, MP, India

Correspondence Address:
P V Lakshmana Rao
Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior - 474002, MP
India
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Source of Support: None, Conflict of Interest: None


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Objective: To evaluate the protective efficacy of certain chemoprotectants against cyclic peptide hepatotoxic microcystin-LR in mice. Material and Methods: Swiss albino female mice were used in all experiments for screening antidotes against the lethal dose of microcystin-LR (100 mg/kg body weight, i.p.). The agents, D-glucose, mannitol, dihydroxyacetone, Trolox®, L-cysteine, N-acetylcysteine, amifostine, glutathione, silymarin, naringin, rifampin and cyclosporin-a were administered as either pre-treatment (1, 3 and 24 h), co-administration or post-treatment. Percent survival and time to death were monitored. The biochemical profile of protected animals was monitored 24 h post-treatment. Results: D-glucose, mannitol, L-cysteine, naringin and amifostine extended the survival time of animals but offered no protection against lethality. N-acetylcysteine, glutathione and Trolox® gave partial protection (25-50%) on pretreatment or co-administration. Complete protection was observed with rifampin (25 mg/kg), cyclosporin-A (10 mg/kg) and silymarin (400 mg/kg) when given as pre-treatment. In addition, rifampin and cyclosprin-A gave complete protection when co-administered with microcystin-LR. Rifampin was the only agent which gave protection at 15 min post-treatment. The biochemical profile of surviving animals 24 h after treatment showed increased liver body weight index and levels of hepatic enzymes viz. LDH, ALT, SDH in serum. Conclusion: Chemoprotectants that can inhibit the specific uptake of toxin into the liver can be promising antidotes against lethal poisoning by microcystin-LR in mice.






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