title: Comparative toxicity evaluation of cyanobacterial cyclic peptide toxin microcystin variants (LR, RR, YR) 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. Over 60 microcystin variants have been reported so far. We report here the results of our study on comparative toxicity evaluation of three most predominant microcystins, MC-LR, MC-RR and MC-YR in mice. The mice were administered one LD(50) dose of MC-LR, RR and YR (43, 235.4 and 110.6 micro g/kg body weight, respectively), and biochemical and histological variables were determined at 30 min post-treatment and mean time to death (MTD). Significant increase in liver body weight index was induced by all three variants. There was marginal increase in serum levels of hepatic enzymes viz. AST, ALT and gamma-GT at 30 min post-treatment but 3-4 fold increase was observed at MTD. In contrast, enhanced LDH leakage, DNA fragmentation and depletion of hepatic glutathione was observed at 30 min post treatment in all three variants. There was no change in levels of serum protein, albumin and albumin/globulin ratio. Liver histology showed time dependent severe pathological lesions like congestion, haemorrhage, portal mononuclear cell infiltration and obliteration of chromatin material. Lung lesions were predominantly in bronchi and parenchyma. Though qualitatively lesions were identical in all three microcystin variants, degree of liver and lung lesions varied quantitatively with the toxin. The breathing pattern and respiratory frequency of the mice after i.p. administration of the toxin showed uniform pattern for 90 min followed by abrupt change in the respiratory pattern and instantaneous death. Based on biochemical and histological studies, MC-LR was found to be the most potent toxin followed by MC-YR and MC-RR.
authors.affiliation: Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, 474002, Gwalior, India. pvlrao@rediffmail.com
authors.forename: Nidhi
authors.initials: N
authors.lastname: Gupta
authors.forename: S C
authors.initials: SC
authors.lastname: Pant
authors.forename: R
authors.initials: R
authors.lastname: Vijayaraghavan
authors.forename: P V Lakshmana
authors.initials: PV
authors.lastname: Rao
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D053938:DNA Fragmentation / Q000187:drug effects; D005260:Female; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D010456:Peptides, Cyclic / Q000633:toxicity*; D015996:Survival Rate; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C065685:microcystin YR; C063855:microcystin RR; D007770:L-Lactate Dehydrogenase; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C057862:cyanoginosin LR