Effect of Pantethine on HDL Production in Normal Rabbits

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  • NAKAYASU Toshiro
    Laboratory of Biochemistry, Research Institute, Daiichi Seiyaku Co., Ltd.
  • WAKASUGI Jun-ichiro
    Laboratory of Biochemistry, Research Institute, Daiichi Seiyaku Co., Ltd.
  • TOMIKAWA Munehiro
    Laboratory of Biochemistry, Research Institute, Daiichi Seiyaku Co., Ltd.
  • ABIKO Yasushi
    Laboratory of Biochemistry, Research Institute, Daiichi Seiyaku Co., Ltd.

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  • パンテチンのウサギHDL増加作用機作

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Effect of pantethine on high density lipoprotein (HDL) cholesterol levels was studied with normolipemic rabbits. When rabbits were treated with pantethine at 1% in diet for 32 days, a significant increase in HDL-cholesterol and apolipoprotein A1 antigen levels in serum was observed without any changes in (V) LDL-cholesterol and apolipoprotein B antigen levels. The increase in HDL-cholesterol was accompanied by a significant increase in triglyceride clearance of injected intralipid or chyromicron/VLDL from the circulating blood. Pantethine also caused a considerable increase in the heparin-releasable lipoprotein lipase activity in the epididymal adipose tissue and LCAT activity in serum. These effects of pantethine strongly suggest a stimulation of “VLDL-HDL Pathway” to produce HDL and to increase HDL-cholesterol values. This was further evidenced by the kinetic study of injected 125I-labeled VLDL in these rabbits. Patethinetreated rabbits showed significantly higher fractional catabolic rates for 125I-labeled apolipoproteins in both VLDL and HDL fractions than control rabbits.<br>On the other hand, the liver perfusion study indicated that a greater amount of apolipoprotein A1 was produced in the liver from pantethine-treated rabbits than in control livers and that incorporation of 3H-labeled leucine into apolipoprotein A1 was increased in the livers from the treated rabbits. No difference was observed in production of apolipoprotein B and albumin in the livers between the 2 groups. A mechanism of the selective or preferential action of Pantethine towards apolipoprotein A1 is not clear yet.<br>In conclusion, pantethine caused an increase in the adipose tissue LPL and serum LCAT activities and in hepatic apolipoprotein A1 synthesis in normal rabbits. These effects may lead to the elevation of HDL levels through acceleration of the “VLDL-HDL Pathway”.

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