ABSTRACT
We previously demonstrated that hyperbaric oxygen (HBO) treatment inhibits diet-induced atherosclerosis in New Zealand White rabbits. In the present study we investigate the mechanisms that might be involved in the athero-protective effect of HBO treatment in a well-accepted model of atherosclerosis, the apoE knockout (KO) mouse. We examine the effects of daily HBO treatment (for 5 and 10 weeks) on the components of the anti-oxidant defense mechanism and the redox state in blood, liver and aortic tissues and compare them to those of untreated apoE KO mice. HBO treatment results in a significant reduction of aortic cholesterol content and decreased fatty streak formation. These changes are accompanied by a significant reduction of autoantibodies against oxidatively modified LDL and profound changes in the redox state of the liver and aortic tissues. A 10-week treatment significantly reduces hepatic levels of TBARS and oxidized glutathione, while significantly increases the levels of reduced glutathione, glutathione reductase (GR), transferase, Se-dependent glutathione peroxidase and catalase (CAT). The effects of HBO treatment are similar in the aortic tissues. These observations provide evidence that HBO treatment has a powerful effect on the redox state of relevant tissues and produces an environment that inhibits oxidation. The anti-oxidant response may be the key to the anti-atherogenic effect of HBO treatment.
Subject(s)
Antioxidants/metabolism , Apolipoproteins E/deficiency , Atherosclerosis/prevention & control , Hyperbaric Oxygenation , Animals , Aorta, Thoracic/pathology , Apolipoproteins E/genetics , Aryldialkylphosphatase/blood , Atherosclerosis/etiology , Atherosclerosis/metabolism , Atherosclerosis/pathology , Autoantibodies/blood , Cholesterol/blood , Female , Glutathione/metabolism , Glutathione Disulfide/metabolism , Lipid Peroxidation , Lipoproteins, LDL/immunology , Liver/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Oxidation-Reduction , Oxidative Stress , Rabbits , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
In the present study the effects of dietary fat with defined fatty acids on lecithin:cholesterol acyltransferase (LCAT) and apoA-1, the two components of HDL that play a major role in reverse cholesterol transport (RCT), were examined. In addition, the expression of scavenger receptor B1 (SR-B1), the receptor involved in the uptake of HDL core lipids, was also determined under the same conditions in rats fed semisynthetic diets supplemented with triolein (TO), tripalmitin (TP) or menhaden oil (MO). Serum LCAT activity [ micro mol CE/(L.h)] was significantly (P < 0.05) higher in rats fed TO (33 +/- 4) compared with those fed TP (23 +/- 3) or MO (21 +/- 1). The levels of hepatic LCAT mRNA and hepatic SR-B1 receptor protein did not differ between rats fed TP and MO. The triolein diet, on the other hand, increased the induction of hepatic LCAT mRNA and hepatic SR-B1 receptor protein 1.5- to 2-fold. Serum HDL cholesterol concentrations differed among all groups and were 1.30 +/- 0.08, 1.17 +/- 0.10 and 0.91 +/- 0.06 mmol/L for TO-, TP- and MO-fed rats, respectively. Serum apoA-1 levels were significantly higher in TO-fed rats than in the other two groups. The data indicate that TO increases the secretion of HDL and its components (apoA-1 and LCAT), and stimulates the production of hepatic SR-B1 receptor protein. Overall, these results suggest that triolein may promote RCT and thus retard the development of atherosclerosis.
