Hepatic lipid peroxidation, sulfhydryl status, and toxicity of the blue-green algal toxin microcystin-LR in mice.
Microcystin-LR (MCLR), a cyclic heptapeptide produced by the blue-green algae Microcystis aeruginosa, produces death in female mice treated with 100 micrograms MCLR/kg. Kupffer-cell hyperplasia was observed histologically after treatment with 50 or 100 micrograms MCLR/kg. No other changes or lethality were observed with the 50 micrograms MCLR/kg, while 100% lethality occurred in less than 2 h in mice treated with 100 micrograms/kg. In these animals liver weights increased by 45% and hepatic hemoglobin content increased 106% at 60 min posttreatment. Liver histology showed loss of hepatic architecture and necrosis 30 min after treatment, and congestion with blood became evident at 45 min after treatment. Serum enzymes were significantly increased 45 min posttreatment. Hepatic nonprotein sulfhydryl content decreased 19% when calculated on the basis of cytosolic protein and 39% when based upon the total protein content, respectively. The sulfhydryl content of the liver cytoskeletal fraction decreased 26% by 30 min after treatment. Decreased enzyme-mediated and increased non-enzyme-mediated lipid peroxidation were observed in hepatic microsomes following both in vivo and in vitro exposure of hepatic microsomes to MCLR. The toxicity of MCLR may be related to alterations in the sulfhydryl content of the cytoskeletal protein. Furthermore, MCLR may either directly or indirectly affect microsomes, suggesting alterations in structure and function of smooth endoplasmic reticulum.
Hermansky
S J
SJ
Department of Pharmaceutical Science, University of Nebraska Medical Center, Omaha.
Stohs
S J
SJ
Markin
R S
RS
Murray
W J
WJ
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002478:Cells, Cultured; D000458:Cyanobacteria; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006454:Hemoglobins / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008387:Marine Toxins; D051379:Mice; D052998:Microcystins; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010456:Peptides, Cyclic / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D014118:Toxins, Biological
D003598:Cytoskeletal Proteins; D006454:Hemoglobins; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D013438:Sulfhydryl Compounds; D014118:Toxins, Biological; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C057862:cyanoginosin LR