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KMID : 0376219810180010115
Chonnam Medical Journal
1981 Volume.18 No. 1 p.115 ~ p.129
Electron Microscopic Study on Rat Liver Cell After Methotrexate Administration

Abstract
To investigate the effects of methotrexate on the rat liver cells, light and electron microscopic observations were made. Animals were injected once in every other day intraperitoneally with methotrexate(0.03mg in small dose group and 0.lmg in large dose group per 100g body weight) and were sacrificed 24 hours after 3, 5, and 7 doses of methotrexate in the cases of small dose group and after 3 and 5 doses of methotrexate in the cases of large dose group. The following results were obtained.
In histological observations, centrilobular hepatocytes with cytoplasmic vacuoles and with degenerative changes were often noted in both groups with hematoxylin-eosin stain. Meganucleus often with vesicular architecture was revealed in Feulgen reaction after 5 and 7 doses in small dose group. With Sudan-IV stain sudanophilic granules were clearly observed in the cytoplasm and nucleus of hepatocytes after 7 doses in small dose group.
In electron microscopic observations of small dose group, there were no appreciable changes in the nucleus, but large fat droplets with homogenous density and slightly decreased amount of glycogen particles were noted in the cytoplasm after 3 doses. After 5 doses significant changes in the nuclei of some hepatocytes were noted. These changes included the appearance of several types of inclusions such as fat droplets, dense bodies and vacuolar structures. These nuclear and cytoplasmic changes were more marked after 7 doses compared with those of 5 doses. Furthermore, structureless empty spaces were present among the coarse filamentous or granular components of the karyoplasm. In the cytoplasm, smooth endoplasmic reticulum, mainly vesicular type, were abundant and often continuous with rough endoplasmic reticulum, and cisternae of Golgi apparatus were somewhat dilated.
In large dose group, nuclear and cytoplasmic changes were more striking than in small dose group. After 3 large doses, nuclear and cytoplasmic fat droplets in the hepatocytes began to appear and cytoplasmic glycogen particles drastically decreased. These changes both in cytoplasm and nucleus of the hepatocytes were pronounced after 5 doses.
In all of the experimental groups, no significant fine structural changes were noted in mitochondria, rough endoplasmic reticulum, microbodies, and lysosomes.
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