Ionizing radiation alters hepatic cholesterol metabolism and plasma lipoproteins in Syrian hamster

Abstract

Purpose: The investigation of the effects of ionizing radiation on hepatic cholesterol metabolism and the concentration and composition of plasma lipoproteins in the male Syrian hamster. Materials and methods: After sublethal whole-body 60Co gamma-irradiation (8Gy, 1Gy/min), plasma lipoproteins were separated by density-gradient ultracentrifugation. Activities of hydroxymethylglutarylCoA (HMGCoA) reductase and of cholesterol 7 alpha hydroxylase were measured in hepatic microsomes and the lowdensity lipoprotein (LDL) receptor mass was determined in hepatic total membranes. Lipid peroxidation in LDL was assessed in vitro as the formation of conjugated dienes at 234nm. A group of pair-fed animals served as controls as the food intake was markedly decreased with exposure to radiation. Results: Plasma lipid concentrations decreased 2 days postirradiation and then markedly increased by day 6 postirradiation; plasma cholesterol was increased by 77% and triglycerides by 207%. LDL accumulated in plasma while high-density lipoprotein (HDL) levels decreased. HDL contained significant amounts of apo SAA, the acute phase apolipoprotein. The activities of hepatic HMGCoA reductase, the rate-limiting enzyme for cholesterol synthesis, increased (+125%, p=0.06); hepatic cholesterol 7 alpha -hydroxylase, the rate-limiting enzyme for bile acid synthesis, decreased (-85%); and the hepatic LDL receptor mass also decreased (-44%). The susceptibility of LDL to oxidation was also increased when animals were exposed to radiation. Conclusions: Lipoprotein modifications that appeared following radiation exposure may result from an induced inflammatory state and may further contribute to vascular damage.