Inhibition of Ca-induced calcium release from mitochondria by antiischemic phenol-based antioxidants

Effects of different inhibitors of lipid peroxidation (LP), such as sulphur-containing oligoquinone hypoxen, natural flavonoid dihydroquercetin (DHQ), and β-ionol, on Ca²⁺-induced calcium release from rat liver mitochondria (RLM) were investigated during oxidation of various substrates. The hypothesis about interrelation between antioxidant properties and influence of selected substances on spontaneous calcium release from mitochondria was verified. Degree of antioxidant activity of the selected substances was estimated by the inhibition of LP induced by Fe²⁺/ATP complex in phospholipid emulsion or in rat liver mitochondria (RLM). According to the inhibition efficacy the investigated substances were ordered as follows: β-ionol ≫ hypoxen > DHQ. 50% inhibition of oxygen consumption during LP of phospholipid emulsion was reached in presence of 3.2 ± 0.6 μM of β-ionol, 15.0 ± 1.1 μM of hypoxen, or 19.8 ± 1.7 μM of DHQ. Among the investigated antioxidants hypoxen only decreased spontaneous release of calcium from RLM after calcium accumulation by RLM. The impact of the antioxidants onto calcium current depended on the oxidized substrate. Hypoxen effect was most expressed during the oxidation of NAD-dependent substrate. The direct relationship between the antioxidant activity of the selected antioxidants and their influence on calcium transport in RLM was not revealed. The results indicate that the choice of antiischemic preparations should not only rely on their antioxidant activities.