Consequences of treatment with dexamethasone in rats on the susceptibilityof total plasma and isolated lipoprotein fractions to copper oxidation

According to the oxidative hypothesis of atherosclerosis, a hyperoxidizabil ity of lipoproteins could favor the development of the atherosclerotic proc ess. Besides, it has been recently reported that models of elevated very-lo w-density-lipoprotein (VLDL) levels in rats resulted in an increased suscep tibility of these VLDL to oxidation. Treatment with dexamethasone classical ly induces an increase in plasma VLDL concentration. The aim of our study w as thus to assess the effects of a treatment with dexamethasone in rats on the susceptibility to copper oxidation, both on total plasma and on isolate d lipoproteins. Male Sprague-Dawley rats aged three months were treated with a daily intrap eritoneal injection of dexamethasone (1.5 mg per kg) for five days (DEX gro up), whereas control rats were fed ad libitum (AL group). In order to take into account the decrease of food intake induced by dexamethasone treatment , a group of pair-fed rats was constituted (PF group). These rats had the s ame food intake as rats of the DEX group and were treated with a daily isov olumic intraperitoneal injection of NaCl for 5 d. After 5 d treatment, rats were fasted overnight, then killed, and blood was collected on EDTA. Low-d ensity lipoproteins (VLDL + LDL) and high-density lipoproteins (HDL) were i solated by ultracentrifugation. A copper oxidation was conducted both on to tal plasma and on isolated lipoproteins. As expected, after treatment with dexamethasone, plasma exhibited increased triglyceride and glucose levels. Similarly, VLDL + LDL of rats from the DE X group were enriched with triglycerides, when compared with VLDL + LDL of the other two groups of rats. Our major finding was a marked increase in th e susceptibility of total plasma of the DEX group to copper oxidation, in c omparison with the other two groups of rats. This oxidizability was assesse d by the maximal level of oxidation products absorbing at 234 nm and classi cally considered to be conjugated dienes (7.46 +/- 0.70 mu mol L-1 in the D EX group vs 3.36 +/- 0.40 and 2.05 +/- 0.60,mu mol L-1 in the AL and PF gro ups, respectively). Nevertheless, th is higher oxidizability was not observ ed in the isolated lipoprotein fractions, as shown by the formation of lipi d peroxidation products such as conjugated dienes, thiobarbituric-acid reac tive substances, hydroperoxides, 7-ketocholesterol, and dienals. This is no t in agreement with other models of hypertriglyceridemia that have been rep orted to induce a hyperoxidizability of lipoproteins in rats, Our results l ed us to hypothesize that other plasma components such as proteins could be involved in this susceptibility to oxidation. Indeed, the severe protein c atabolism induced by dexamethasone treatment could support this hypothesis, by forming protein components that are more susceptible to oxidation, as s hown by an increased carbonyl formation upon plasma copper oxidation.