Toxicity and chemical form of selenium in the liver of mice orally administered selenocystine for 90 days.
The subacute oral toxicity of selenocystine and chemical form of selenium in the liver following exposure to this compound were assessed in ICR male mice. Animals were dosed 6 days/week for 30, 60 or 90 days with 0, 5, 10 or 15 mg/kg per day. Body weight gain decreased with dosage. The activities of aspartate aminotransferase and alanine aminotransferase in plasma were significantly elevated at the highest dose level after 60 days and at the two higher dose levels after 90 days of exposure. However, the level of selenium content in the liver was the same at the two higher dosages at both 60 and 90 days of exposure. The subcellular distribution of selenium in the liver from mice treated with selenocystine showed that the major part of the total selenium content, 68.3-72.1%, existed in the cytosolic fraction. Sephadex G-150 chromatograms of liver cytosol of the animals administered selenocystine revealed three selenium-containing fractions which involve glutathione peroxidase (molecular weight 80,000) high molecular (molecular weight 55,000-60,000) and low molecular (molecular weight < 10,000) substances. Selenium content and acid-volatile selenium content in the high molecular weight fraction increased with exposure time to selenocystine. Thus, in a subacute toxicity study selenocystine given for 90 days caused hepatic damage in mice, depending on the acid-volatile selenium content in the liver cytosol.
Hasegawa
T
T
Division of Environmental Health, Faculty of Pharmaceutical Sciences, Setsunan University, Osaka, Japan.
Taniguchi
S
S
Mihara
M
M
Nakamuro
K
K
Sayato
Y
Y
D000284:Administration, Oral; D000818:Animals; D002850:Chromatography, Gel; D003553:Cystine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D003600:Cytosol / Q000378:metabolism; D004334:Drug Administration Schedule; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D012643:Selenium / Q000032:analysis / Q000378:metabolism*; D013347:Subcellular Fractions
D016566:Organoselenium Compounds; C009226:selenocystine; D003553:Cystine; D012643:Selenium