Ferrous-iron induces lipid peroxidation with little damage to energy transduction in mitochondria

Abstract

Addition of ferrous sulfate, but not ferric chloride, in micromolar concentrations to rat liver mitochondria induced high rates of consumption of oxygen. The oxygen consumed was several times in excess of the reducing capacity of ferrous-iron (O:Fe ratios 5-8). This occurred in the absence of NADPH or any exogenous oxidizable substrate. The reaction terminated on oxidation of ferrous ions. Malondialdehyde (MDA), measured as thiobarbituric acid-reacting material, was produced indicating peroxidation of lipids. The ratio of O2:MDA was about 4:1. Pretreatment of mitochondria with ferrous sulfate decreased the rate of oxidation (state 3) with glutamate (+ malate) as the substrate by about 40% but caused little damage to energy transduction process as represented by ratios of ADP:O and respiratory control, as well as calcium-stimulated oxygen uptake and energy-dependent uptake of [45Ca]-calcium. Addition of succinate or ubiquinone decreased ferrous iron-induced lipid peroxidation in intact mitochondria. In frozen-thawed mitochondria, addition of succinate enhanced lipid peroxidation whereas ubiquinone had little effect. These results suggest that ferrous-iron can cause peroxidation of mitochondrial lipids without affecting the energy transduction systems, and that succinate and ubiquinone can offer protection from damage due to such ferrous-iron released from the stores within the cells.

Effects of idoxifene and estradiol on NF‐κB activation in cultured rat hepatocytes undergoing oxidative stress

“…Liver mitochondria were prepared from 250–300‐g male Wistar rats. Lipid peroxidation in isolated rat liver mitochondria after freezing overnight and thawing the next day (26) was measured by monitoring oxygen consumption in the presence of iron (II) sulfate heptahydrate (FeSO 4 ) and adenine diphosphate with or without idoxifene, estradiol, and tamoxifen (0.2, 1, 2, 5, and 10×10 −6 mol/l), as described elsewhere (23, 25). The inhibition rate (%) of each sample against lipid peroxidation was calculated based on the amount of consumed oxygen as shown in Fig.…”

Effects of Sho–Saiko–To, A Japanese Herbal Medicine, on Hepatic Fibrosis in Rats

“…Lipid peroxidation in isolated rat liver mitochondria (0.7 mg/mL) after freezing overnight and thawing next day 38 was measured by monitoring oxygen consumption at 25°C with a Clark-type oxygen electrode in the presence of 1 mmol/L adenine diphosphate and 100 mmol/L iron (II) sulfate heptahydrate (FeSO 4 ), and in the presence or absence of TJ-9 (0.1, 0.2, 1, and 5 mg/mL), in a total volume of 2.53 mL 10 mmol/L Tris-HCl (pH 7.5), 175 mmol/L KCl. The amount of oxygen consumed was calculated from the assumption that the saturated concentration of oxygen at 25°C is 258 µmol/L.…”

Oxidants act as chemorepellents in Paramecium by stimulating an electrogenic plasma membrane reductase activity

“…Since it can reduce iron (Table 1), it could also be involved in Fe +++ uptake. Excess reduced iron may also be deleterious because of iron-induced lipid peroxidation (Shivaswamy et al 1993). Another recent theory suggests that Paramecium may have evolved an ability to avoid compounds in the environment that it would never normally expect to see because they are common cytoplasmic constituents of live cells.…”