Toxic response indicators of microcystin-LR in F344 rats following a single-dose treatment.
Microcystin-LR (MCLR) is the most common hepatotoxic cyanotoxin produced primarily by Microcystis aeruginosa. In this study, young F344 rats were intraperitoneally injected with a single dose (25, 50, 100, and 150 microg/kg) of MCLR to explore possible toxic effect and toxic response indicators. Acute toxic symptoms, including body weight loss and death, were monitored for 7 days. Mortality reached 100% (9/9) in rats treated with a single MCLR dose of 150 microg/kg. Histopathological examination showed spot necrosis in the liver of animals treated at low doses, while massive hemorrhage and widespread necrotic foci occurred at higher doses, indicating extensive liver damage. Protein phosphatase 2A (PP2A) expression showed a dose-dependent decrease in the liver. Immunohistochemical localization indicated that nuclear PP2A was affected first, followed by cytoplasmic PP2A. In addition, there was a significant increase in sphingolipid levels at higher doses, indicating the involvement of a ceramide-mediated apoptotic pathway. Expression of apoptosis and cell cycle regulatory proteins like Bax, Bcl2, and Bad showed a dose-dependent decrease. This study demonstrated that treatment with a single dose of MCLR caused liver damage, increased sphingolipid levels, and decreased PP2A expression, which ultimately down-regulated the expression of Bcl2 family proteins.
Billam
Madhavi
M
Department of Environmental Toxicology, The Institute of Environmental and Human Health, Texas Tech University, Box 41163, Lubbock, TX 79409-1163, USA.
Mukhi
Sandeep
S
Tang
Lili
L
Gao
Weimin
W
Wang
Jia-Sheng
JS
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D052998:Microcystins / Q000633:toxicity*; D009026:Mortality; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D018797:Cell Cycle Proteins; D008387:Marine Toxins; D052998:Microcystins; D054648:Protein Phosphatase 2; C057862:cyanoginosin LR