Korean J Phys Anthropol.  1998 Jun;11(1):95-109.

Effects of DMTU on Adriamycin Induced Changes in Ultrastructure of Hepatocytes in Growing and Adult Rats

• Paik DJ
• Kang YW
• Ahn DC
• Chang KH
• Chung HS

Abstract

Adriamycin has been widely used as an anticancer drug in the treatment of thyroid tumor, metastatic breast cancer, sarcoma and lymphoma. The antineoplastic effects of adriamycin result from its inhibitory action on the nucleic acid synthesis and the formation of reactive oxygen radicals by redoxcycling during its metabolic process. Adriamycin affects the normal cells of the patients and causes the undesirable side effects and the toxic effects. Thus, in this study we investigated the effect of dimethyl thiourea (DMTU), a hydroxyl radical scavenger, on the ultrastructural changes of the hepatocyte after the administration of adriamycin in the growing and adult rats. 36 Healthy male Sprague -Dawley adult rats (about 350 g) and 36 male rats at growing peroid (about 120 g) was used as experimental animals. Adriamycin (25 mg/kg) was administered intraperitoneally and DMTU (500 mg/kg) was administered intraperitoneally 30 minutes after the administration of adriamycin. The rats were sacrificed at 24 hours and 72 hours after the administration of adriamycin. A part of the liver from left anterior lobe was obtained and sliced into about 1 mm 3 . The specimens were prepared by the routine methods for electron microscopy. All preparations were stained with uranyl acetate and lead citrate and observed with Hitach -600 electron microscope. The results were as follows. 1. In the hepatocytes of the adult rat dilated, segmented and ribosome detached cisternae of rough endoplasmic reticulum, increased and dilated cisternae of smooth endoplasmic reticulum, damaged mitochondria and autophagic vacuoles were seen after the administration of adriamycin. The ultrastructural changes were progressive with the lapse of time. 2. In the hepatocyte of the growing rat dilated and ribosome detached cisternae of rough endoplasmic reticulum, changes of mitochondria, many lysosomes and the autophagic vacuoles were observed after the administration of adriamycin. 3. DMTU alone did not affect the ultrastructures of the hepatocytes in both growing and adult rats. 4. In the hepatocytes of growing and adult rats, dilated and ribosome detached cisternae of rough endoplasmic reticulum, dilated and increased cisternae of smooth endoplasmic reticulum, changes of mitochondria and autophagic vacuoles were seen after the combined administration of adriamycin and DMTU, but the degree of ultrastructural changes was

MeSH Terms

Adult*
Animals
Breast Neoplasms
Citric Acid
Doxorubicin*
Endoplasmic Reticulum, Rough
Endoplasmic Reticulum, Smooth
Hepatocytes*
Humans
Hydroxyl Radical
Liver
Lymphoma
Lysosomes
Male
Metabolism
Microscopy, Electron
Mitochondria
Rats*
Reactive Oxygen Species
Ribosomes
Sarcoma
Thiourea
Thyroid Gland
Vacuoles
Citric Acid
Doxorubicin
Hydroxyl Radical
Reactive Oxygen Species
Thiourea