title: Protective efficacy and the recovery profile of certain chemoprotectants against lethal poisoning by microcystin-LR in mice.
abstract: The cyclic peptide toxins microcystins and nodularins are the most common and abundant cyanotoxins present in diverse water systems. They have been the cause of human and animal health hazards and even death. Development of suitable chemoprotectants against microcystin is essential considering the human health importance. In the present study, three agents cyclosporin-A (10mg/kg), rifampin (25mg/kg) and silymarin (400mg/kg) pre-treatment gave 100% protection against lethal dose of microcystin-LR (100 microg/kg). Various biochemical parameters were evaluated to study the recovery profile of protected animals at 1, 3, 7 and 14 days post-toxin treatment. There was significant depletion of hepatic glutathione in protected animals compared to control group till 7 days post-treatment but normalised by 14 days. Similarly enhanced hepatic lipid peroxidation, inhibition of protein phosphatase activity was observed till 3-7 days post-treatment in protected animals. Elevated levels of enzymes alanine amino transferase, lactate dehydrogenase and sorbitol dehydrogenase were observed in serum at 1 day post-treatment. All the biochemical variables reached control levels by 14 day post-treatment. Immunoblotting analyses of liver homogenates showed microcystin-protein phosphatase adduct in liver samples of toxin treated as well as antidote-protected animals. The adduct could be seen even after 14 days post-toxin treatment. The study shows that though cyclosporin-A, rifampin and silymarin could offer 100% protection against microcystin-LR induced lethality many of the toxic manifestations are persistent and could not be reversed till 7 days.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India. pvlrao@rediffmail.com
authors.forename: P V Lakshmana
authors.initials: PV
authors.lastname: Rao
authors.forename: R
authors.initials: R
authors.lastname: Jayaraj
authors.forename: A S B
authors.initials: AS
authors.lastname: Bhaskar
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001427:Bacterial Toxins / Q000506:poisoning*; D015153:Blotting, Western; D000458:Cyanobacteria / Q000737:chemistry*; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007064:L-Iditol 2-Dehydrogenase / Q000097:blood; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects*; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D010456:Peptides, Cyclic / Q000506:poisoning*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology; D012838:Silymarin / Q000494:pharmacology; D013050:Spectrometry, Fluorescence
chemical_list: D001427:Bacterial Toxins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D020011:Protective Agents; D012838:Silymarin; D016572:Cyclosporine; D007064:L-Iditol 2-Dehydrogenase; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR; D005978:Glutathione; D012293:Rifampin