Damage to macrophages by tert-butyl hydroperoxide and the protective action of the protein bound polysaccharide krestin

Abstract

Previous work has shown that lipoperoxidative damage to macrophages caused by oxidatively modified low-density lipoprotein (O-LDL) plays an important role in foam cell formation, and that the polysaccharide krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, can protect macrophages from foam cell formation caused by O-LDL and from damage to physiological functions induced by tert-butyl hydroperoxide (tbOOH). In order to demonstrate further the mechanism of lipoperoxidative damage in foam cell formation caused by O-LDL, we investigated the damage to macrophage ultrastructure induced by tbOOH, protection by PSK and its action mechanism. Macrophages incubated with tbOOH showed morphological changes under the transmission electron and scanning electron microscope, their survival rate was decreased markedly, and the effects could be prevented and alleviated by PSK. As compared with a non-PSK treated group, selenium dependent glutathione peroxidase (SeGSHPx) and non-selenium dependent glutathione peroxidase (non-SeGSHPx) activities, manganese superoxide dismutase (MnSOD) activity and mRNA content increased significantly in the PSK-treated group. These findings and previous studies taken together suggest that protection by PSK is due to the induction of gene expression of antioxidative enzymes, SeGSHPx, non-SeGSHPx and MnSOD, in the macrophages.