Anticancer therapy with doxorubicin (DOX) and other quinone anthracyclines is limited by severe cardiotoxicity, reportedly because semiquinone metabolites delocalize Fe(II) from ferritin and generate hydrogen peroxide, thereby promoting hydroxyl radical formation and lipid peroxidation. Cardioprotective interventions with antioxidants or chelators have nevertheless produced conflicting results....

Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are a class of genotoxic environmental contaminants. We have long been interested in determining the mechanisms by which nitro-PAHs induce genotoxicity. Although the metabolic activation of nitro-PAHs leading to toxicological activities has been well studied, the photo-induced activation of nitro-PAHs has seldom been reported. In this paper, w...

The relationship between adenylate cyclase activity in the synaptic membrane fraction (M1) of rat brain and lipid peroxidation of these membranes was examined. In the presence of 5 mM dithiothreitol (DTT), 1 to 10 microM Fe/+ activated adenylate cyclase 2- to 4-fold. Of several metal ions, Fe2+ was the most effective. Other enzymes in M1, such as Mg2+-ATPase, (Na+-K+)-ATPase, 5'-nucleotidase, a...

Lipid peroxidation of lipoprotein(a) [Lp(a)] by defined oxygen-centred free radicals (O2-/OH, O2-, O2-/HO2) produced by gamma radiolysis was compared with that of paired samples of low-density lipoprotein (LDL). Lp(a) appeared to be more resistant to oxidation than LDL, as indicated by the kinetic study of four markers of lipid peroxidation; decrease in vitamin E, formation of conjugated dienes...

The effects of L-cysteine on mitochondrial DNA (mtDNA) in mouse brain were investigated both in vivoandin vitro. An intracerebroventricular (icv) injection of L-cysteine (1.25 micromol/animal) caused mtDNA damage in brain frontal and central portions of the cortex, broad-spectrum limbic and severe sustained seizures in mice, and increased lipid peroxidation in the whole brain. The L-cysteine-me...

Addition of thenoyltrifluoracetone to mitochondria oxidizing NAD-dependent substrates induced lipid peroxidation and uncoupling of oxidative phosphorylation. Butylated hydroxytoluene, an antioxidant, prevented accumulation of lipid peroxidation products but failed to prevent deenergization of the mitochondria.

The effect of peroxidative stress on tissue was studied by exposure of red blood cells (RBC) from patients with abetalipoproteinemia to minute amounts of H(2)O(2)in vitro. Red blood cells from untreated patients showed a marked sensitivity to H(2)O(2), as evidenced by hemolysis and lipid peroxidation (peroxidative hemolysis). The appearance of lipid peroxidation products in sensitive cells afte...

We have shown that oxidative stress is a mechanism of free fatty acid (FFA)-induced β-cell dysfunction. Unsaturated fatty acids in membranes, including plasma and mitochondrial membranes, are substrates for lipid peroxidation, and lipid peroxidation products are known to cause impaired insulin secretion. Therefore, we hypothesized that mice overexpressing glutathione peroxidase-4 (GPx4), an enz...

Nitric oxide ((*)NO) can protect cells against the detrimental effects of reactive oxygen species. Using low-density lipoprotein as well as model systems, it has been demonstrated that (*)NO can serve as a chain-breaking antioxidant to blunt lipid peroxidation. To test the hypothesis that (*)NO can serve as a chain-breaking antioxidant in cell membranes, we examined the effect of (*)NO on iron-...

Plasma membranes isolated from the fast-growing, maximal-deviation, Morris hepatoma 3924A exhibit remarkable changes in lipid composition, lipid peroxidation and to some extent in the physical state with respect to rat liver plasmalemmas. A correlation appears to exist between the lower phospholipid: protein ratio, higher cholesterol: phospholipid ratio, lower rate of lipid peroxidation and dec...