Effect of microcystin-LR (MCLR) on hepatic microsomal membrane fluidity.
Microcystin-LR (MCLR) is a potent cyclic heptapeptide hepatotoxin which appears to cause death due to hemorrhagic shock secondary to blood loss from the vasculature into the damaged liver. The molecular mechanism of toxicity is not known. Previous studies have demonstrated altered hepatic sulfhydryl status and enhanced lipid peroxidation following exposure of mice to MCLR. In the present study, mice were treated with 100 micrograms MCLR/kg and killed 10, 20 or 30 min post-treatment. Significant time-dependent decreases in hepatic microsomal membrane fluidity occurred. When microsomes from control animals were incubated in vitro with various concentrations of MCLR, no alterations in membrane fluidity were observed. The results suggest that MCLR-induced alterations in microsomal membrane fluidity involve an indirect and secondary effect rather than a direct interaction of the toxin with the membranes.
Hermansky
S J
SJ
Department of Pharmaceutical Sciences, School of Pharmacy and Allied Health Professions, Creighton University, Omaha, NE 68178.
Stohs
S J
SJ
D000818:Animals; D005260:Female; D005454:Fluorescence Polarization; D008051:Lipid Bilayers / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008387:Marine Toxins / Q000633:toxicity; D008560:Membrane Fluidity / Q000187:drug effects*; D051379:Mice; D052998:Microcystins; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000633:toxicity*
D008051:Lipid Bilayers; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; C057862:cyanoginosin LR