Effects of defibrotide on aorta and brain malondialdehyde and antioxidantsin cholesterol-induced atherosclerotic rabbits

The effects of a high-cholesterol diet in the presence and absence of defib rotide, a single-stranded polydeoxyribonucleotide compound, on the lipid pe roxidation product malondialdehyde, endogenous antioxidant enzymes catalase , glutathione peroxidase, and the antioxidant thiol compound GSH were inves tigated. Forty male New Zeland white rabbits were divided into four groups each consisting of 10 rabbits. Group I received a regular rabbit chow diet and group II 1% cholesterol plus regular chow, group III was given defibrot ide (60 mg/kg per day p.o. in water) and was fed with regular chow, and gro up IV received defibrotide plus 1% cholesterol for 9 weeks. Blood cholester ol and malondialdehyde, catalase, glutathione peroxidase, and GSH were dete rmined before starting the experimental diet regimen (basal). After 9 weeks , the same parameters were determined in blood, aorta, and brain tissues (e nd -experiment). Aortic tissue was examined under a light microscope for mo rphological alterations indicative of atherosclerosis. The increase in seru m total cholesterol was greater in group II than group IV. Plasma malondial dehyde in group II was higher than in group III. Brain malondialdehyde in g roup II was higher than all other groups, and aortic malondialdehyde in thi s group was higher than group I and III. Serum catalase activity decreased in group II and increased in group III, compared with basal values. Brain c atalase activity in group I was higher than group II, and aorta catalase in group IV was higher than in group I and III. Blood glutathione peroxidase activity in group III and IV was higher than basal. GSH concentrations decr eased significantly in the cholesterol-fed groups (group II and IV). Histol ogical alterations in the cholesterol-fed groups were mon pronounced in gro up II. The increased levels of malondialdehyde in plasma, aorta, and brain tissue of group II suggest a role of oxygen foe radicals in the pathogenesi s of cholesterol-induced atherosclerosis. The higher malondialdehyde values in the brain tissues of animals in group II compared with group IV suggest a protective role of defibrotide in the brain against lipid peroxidation i n the oxidant stress of cholesterol-induced atherosclerosis. Increased cata lase activities in the blood and aortic tissues and increased glutathione p eroxidase activities in the blood of rabbits receiving defibrotide suggest an induction of these antioxidant enzyme activities by defibrotide. These r esults imply that anti-atherosclerotic, anti-ischemic effects of this drug may be due to the beneficial effects on the oxidant-antioxidant balance of various tissues.