Acute oral toxicity of microcystin-LR, a cyanobacterial hepatotoxin, in mice
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T Yoshida1, Y Makita, S Nagata
1Toxicology Division, Institute of Environmental Toxicology, Ibaraki, Japan.
Abstract:
Microcystin-LR (MCLR) is a hepatotoxic peptide produced by Microcystis aeruginosa, an alga found worldwide in reservoirs for drinking supply; however, acute oral toxicity of purified MCLR remains unknown. Therefore, a single dose of MCLR (more than 95% purity) ranging from 8.0 to 20.0 mg/kg body weight was orally given to female 6-week old BALB/c mice, and lethality and pathological changes were observed. Median lethal dose (LD50) of the orally given MCLR estimated by the up and down method was 10.9 mg/kg, which was 167 times higher than the i.p. LD50 value (65.4 microgram/kg by moving average method). Orally administrated toxin caused primarily hepatocellular injuries with characteristics of hemorrhage and necrosis. In situ end-labeling as well as electron microscopic observation revealed an induction of apoptotic cell death to hepatocytes. These results indicate the lethality of MCLR was much lower in oral dosage than by i.p. administration, but toxic effects are similar. In addition, apoptosis is considered one of major components in MCLR-induced hepatotoxicity.
Insights
Acute oral toxicity of Microcystin-LR (MCLR) in mice was determined. Oral MCLR showed significantly lower lethality than intraperitoneal injection, but caused similar liver damage, including apoptosis.
Area of Science:
- Environmental Toxicology
- Hepatotoxicity Research
- Cyanobacterial Toxin Analysis
Background:
- Microcystin-LR (MCLR) is a potent hepatotoxin produced by Microcystis aeruginosa, a common freshwater alga.
- MCLR is a concern for drinking water safety due to its presence in global reservoirs.
- The acute oral toxicity of purified MCLR has not been previously established.
Purpose of the Study:
- To determine the acute oral toxicity and lethal dose (LD50) of purified Microcystin-LR (MCLR) in mice.
- To investigate the pathological changes and cellular mechanisms induced by oral MCLR administration.
- To compare the oral toxicity of MCLR with its known intraperitoneal toxicity.
Main Methods:
- Female BALB/c mice were administered single oral doses of purified MCLR (purity >95%) ranging from 8.0 to 20.0 mg/kg body weight.
- Lethality and pathological alterations in liver tissues were observed.
- Median lethal dose (LD50) was estimated using the up-and-down method.
- Apoptosis was detected using in situ end-labeling and electron microscopy.
Main Results:
- The estimated median lethal dose (LD50) for oral MCLR administration was 10.9 mg/kg.
- Oral LD50 was 167 times higher than the reported intraperitoneal LD50 (65.4 µg/kg).
- Oral MCLR induced hepatocellular injuries, including hemorrhage and necrosis, and triggered apoptotic cell death in hepatocytes.
Conclusions:
- The acute lethality of Microcystin-LR is significantly lower via oral exposure compared to intraperitoneal injection.
- Hepatotoxicity induced by oral MCLR involves similar pathological changes and cellular damage, notably apoptosis.
- Apoptosis is a key mechanism contributing to Microcystin-LR-induced liver damage.