Comparison of hepatotoxicity caused by mono-, di- and tributyltin compounds in mice.
The in vivo induction of hepatotoxicity, as evaluated by the activity of ornithine carbamyl transferase in serum, was investigated in mice administered orally with the following three butyltin compounds: tributyltin chloride (TBTC), dibutyltin dichloride (DBTC) and monobutyltin trichloride (MBTC). The minimal concentrations of TBTC and DBTC that caused hepatotoxicity at 24 h after oral administration were 180 mumol and 60 mumol/kg, respectively, while MBTC did not induce liver injury even at 7000 mumol/kg. Additionally, when the administered doses were equivalent (180 mumol/kg), a time course (3-96 h) study revealed that the hepatotoxicity of TBTC and DBTC appeared at 24 and 12 h, respectively, but that MBTC showed no hepatotoxicity even at 96 h. The amounts of Sn excreted into urine for 4 days were 1.5 fold greater with TBTC than with DBTC treatment and were lowest in MBTC group. Similarly, the total liver Sn content was 2- to 5-fold greater in the TBTC group than in the DBTC group whereas the liver Sn content in the MBTC treatment showed the lowest value throughout the 3- to 96-h period. Thus, the non-hepatotoxicity of MBTC may be due either to low absorption through the digestive tract of mice or to the low levels of Sn in liver; however, the level of Sn in liver was not associated with the induction of hepatotoxicity by TBTC and DBTC.(ABSTRACT TRUNCATED AT 250 WORDS)
Ueno
S
S
Department of Veterinary Public Health, School of Veterinary Medicine and Animal Sciences, Kitasato University, Aomori, Japan.
Susa
N
N
Furukawa
Y
Y
Sugiyama
M
M
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D051379:Mice; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D009954:Ornithine Carbamoyltransferase / Q000097:blood; D013723:Teratogens / Q000633:toxicity*; D014001:Tin / Q000378:metabolism / Q000652:urine; D014220:Trialkyltin Compounds / Q000008:administration & dosage / Q000633:toxicity*
D005609:Free Radicals; D009947:Organotin Compounds; D013723:Teratogens; D014220:Trialkyltin Compounds; C011559:tributyltin; D014001:Tin; C048581:monotributyltin trichloride; D009954:Ornithine Carbamoyltransferase; D005978:Glutathione; C020735:dibutyldichlorotin