Antioxidant properties, autooxidation, and mutagenic activity of echinochrome a compared with its etherified derivative.

Antioxidant properties of 2,3,5,7,8-pentahydroxy-6-ethyl-1,4-naphthoquinone (echinochrome A) were linked with the scavenging of peroxy radicals in liposomes, trapping of superoxide anion radicals, and binding of ferrous ions to inactive complexes in the aqueous phase. The antioxidant property of 6-ethyl-2,3,7-trimethoxy-5,8-dihydroxy-1,4-naphthoquinone (trimethoxyechinochrome A) was negligible. Autooxidation of echinochrome A was increased in basic media according to the degree of its dissociation. Autooxidation of polyvalent anions in basic media was accompanied by generation of naphthosemiquinone and superoxide anion radicals as free radical intermediates. An increased rate of echinochrome A autooxidation was noted in the presence of calcium ions. This was explained by a shift of pK of Ca2+-echinochrome A complexes toward acidic pH comparably with echinochrome A. Echinochrome A possessed pronounced mutagenic activity, while trimethoxyechinochrome A was inactive in the Salmonella/mammalian microsome reverse mutation assay (Ames test) for all examined cells (TA98, TA100, TA1537). Comparison of the chemical and biological activity of echinochrome A and trimethoxyechinochrome A demonstrated the key role of the beta-hydroxyl groups in the 2nd, 3rd, and 7th naphthol cycle positions. The O2-* and naphthosemiquinone radicals generated in the redox transition of 2,3-oxygroups may be the reason for the strongly pronounced mutagenicity of echinochrome A.

Myocardial adaptation to long-term action of substances associated with decreased intensity of cardiac function.

The effect of prolonged treatment of rats with 6-n-propyl-2-thiouracil (PTU), verapamil, or propranolol on cardiac pump function and the properties of myofibrils and mitochondria was studied. After 6-8 weeks of treatment, the heart rate and maximal cardiac output of the isolated heart of rats treated with verapamil or propranolol were higher than those in the control group. The PTU treatment was followed by lower heart rate and maximal work. Calcium sensitivity (pCa50 value) of skinned ventricular fibers was higher in all experimental groups compared to the control by 0.07-0.15 units. Myofibrillar Mg2+, Ca(2+)-ATPase activity measured in isolated Triton-skinned cardiomyocytes was considerably lower after PTU treatment than that in respective controls (0.128 +/- 0.013 vs 0.178 +/- 0.010 mumol Pi/min/mg protein). In contrast, long-term treatment with verapamil or propranolol was accompanied by increased activity to 0.223 +/- 0.018 and 0.254 +/- 0.015 mumol Pi/min/mg protein, respectively. Neither the basal mitochondrial respiration rate of saponin-skinned cardiac fibers nor its enhancement after addition of low ADP concentration or creatine was significantly altered in any experimental group. Also no difference between control and experimental groups was observed in the total activity of creatine kinase or relative percentage of its isoenzymes extracted from cardiac tissue. Thus the changes in cardiac pump function after prolonged treatment with agents decreasing cardiac function may be attributed to concomitant alterations of myofibrils while mitochondria remain relatively intact.

Contractile properties and creatine kinase activity of myofilaments following ischemia and reperfusion of the rat heart.

After prolonged ischemia followed by reperfusion of the isolated rat heart, irreversible heart failure is associated with creatine kinase leakage from the cells. The possible implications of MM creatine kinase leakage from myofibrillar compartments on the contractile properties of ventricular muscle have been studied in control versus ischemic hearts. Total creatine kinase activity decreased in ischemic cells while creatine kinase and ATPase activities were not modified in isolated myofibrils. The efficiency of creatine kinase and phosphocreatine in the relaxation of rigor tension in skinned ventricular preparations was not changed after ischemia. Furthermore, neither the pCa/tension relationship nor the rate of tension development following length changes were modified by ischemia. These results show that the contractile properties of myofilaments as well as the functional coupling between myosin ATPase and creatine kinase are preserved in ischemic hearts suffering irreversible contractile failure.