Methotrexate (0.1-2.0 mg/kg/day) with calcium folinate (0.01-0.2 mg/kg/day) was intravenously administered to the male Wister rats and its cytotoxic effects on the hepatic tissue were chronologically investigated to prove the morphological evidences of protective effect by calcium folinate. Animals were divided into 6 groups; 3 control groups of saline only, MTX and CF administration, and another 3 experimental groups of MTX with CF according to the amount. They were sacrificed after 1 to 5 days, and hepatic parenchymal alterations were examined by conventional light and electron microscopes.
1. Small and massive doses of MTX administration resulted in varying degree of ultrastructural changes of the liver in parallel with the cumulative amount of MTX.
2. MTX-induced hepatic injury was manifested with the features of cytotoxic insults, which were predominantly reflected by fine fat droplet, aside from minor changes including irregularity of mitochondria, decreased amount of glycogen particle, dilatation of endoplasmic recticulum, detachment of ribosome, increase of lysosomal bodies, decrease of nuclear heterochromatin and nucleolar laterations.
3. Administation of CF to MTX-treated animals resulted in similar nature of mild ultrastructural changes, but steatosis of mild degree persisted aside from activation of nuclear heterochromatin aggregation.
With the above features it is assumed that administration factor minimizes the ultrastructural alterations of cytotoxic hepatic injuries.
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