Hepatic necrosis in aged mice by oral administration of microcystin-LR.

Aged mice (32 weeks) were orally administered microcystin-LR at 500 micrograms/kg, and injuries of the liver were estimated by microscopy 2 hr after treatment. Sixty-two per cent of aged mice proved to be sensitive to microcystin-LR, whereas such changes in the liver were not found in young mice (5 weeks). Uptake of the toxin into the liver was confirmed by high-performance liquid chromatography and frit-fast atom bombardment liquid chromatograph/mass spectrometry after clean-up with an immunoaffinity column. To verify the difference in sensitivity to microcystin-LR between aged and young mice, non-treated mice were examined, and among them aged mice were confirmed to have a rough surface of the stomach and small intestinal mucosa. These results suggested that the hepatotoxicity by oral administration of microcystin-LR is deeply related to aging, and particularly to conditions in the small intestine such as the permeability of capillaries in the villi.