トリフェニルスズ経口投与による家兎高脂血症とその発生機序について

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Recent laboratory research indicated that triphenyltin fluoride (TPTF) causes a marked increase in the amounts of triglyceride (TG), cholesterol (T-Ch) and phospholipid (PL) in rabbit plasma. The purpose of the present study was to clarify the mechanism causing TPTF hyperlipemia. Male rabbits were given a single oral dose of 5% TPTF in sesame oil at the rate of 0.1g per kg body weight. To determine postheparin lipolytic activity (PHLA), blood was withdrawn after 300 units of heparin was injected. The results obtained were as follow:(1) Lipemia occurred regularly in all animals within 2 days after TPTF administration. TG and T-Ch also showed remarkable increases, the former rising to levels as high as 3, 000mg/dl plasma. However, both TG and T-Ch returned to previous levels within the subsequent 2 weeks.(2) Most liver and renal function tests were within normal ranges except that there were slight increases in GOT and total bilirubin in serum and glucose appeared in the urine.(3) The lipoprotein which accumulated in the plasma was found by density gradient centrifugation to be of a chylomicron and a very low density type (VLDL).(4) PHLA, plasma lipoprotein lipase (LPL) and adipose tissue LPL activity decreased rapidly after TPTF administration and this level remained constant for the two-week observation period. The degree to which tissue LPL activity was reduced was greater than for plasma LPL activity.(5) PHLA and LPL amounts released into plasma by heparin were less and were maintained for a shorter duration in the TPTF group when compared with the control group.(6) Tin levels in adipose tissue increased in the first day after administration, but low levels were observed thereafter.(7) In the range of concentrations 10-3 to 10-7, TPTF and its metabolites (di-, monophenyltin and inorganic tin) did not inhibit LPL activity in vitro. In rabbits, TPTF-induced hyperlipemia is classified as type V following the classifications devised by the World Health Organization. The results further suggest for abnormal patterns that hyperlipemia is caused by the reduced synthesis of LPL in tissues. Therefore, TPTF-induced hyperlipemia in rabbits may be used not only as a model for type V hyperlipemia, but the sensitive reactions of PHLA and LPL activity in plasma to TPTF may be used as an index TPTF exposure.
日本衛生学会の論文

トリフェニルスズ経口投与による家兎高脂血症とその発生機序について

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