Abstract
This study was designed to clarify the role of phospholipase in the mechanism of plasmocid-induced mitochondrial dysfunction in the rat heart. Rats were divided into two groups: the control group, untreated; and the plasmocid group,in which plasmocid (30 mg/kg) was injected subcutaneously. In each group,the level of lipid peroxides and the phospholipase activity in heart homogenate were measured, and mitochondrial function (respiratory control index and the rate of oxygen consumption in State III) was determined polarographically. The activity of lysosomal enzymes (N-acetyl-β-glucosaminidase and β-glucuronidase) were also measured. The plasmocid group showed significant increases in lipid peroxide levels and phospholipase activity. Administration of plasmocid also caused mitochondrial dysfunction, while no significant changes were observed in the lysosomal enzyme activity of either group. These results suggested that plasmocid induced mitochondrial dysfunction is based on the degrading of phospholipids by membrane bound phospholipase, and that lysosomal enzymes are unlikely to be involved in plasmocid-induced mitochondrial dysfunction.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Ajioka M, Sugiyama S, Ogawa K, Satake T, Ozawa T (1986) Mechanism of cardiac arrhythmias induced by epinephrine in dogs with hypokalemia. J Am Coll Cardiol 8: 1373–1379
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37: 911–917
Chien KR, Abrams J, Serroni A, Martin JT, Farber JL (1978) Accelerated phospholipid degradation and associated membrane dysfunction in irreversible, ischemic liver cell injury. J Biol Chem 253: 4809–4817
D'Agostino AN (1963) An electron microscopic study of skeletal and cardiac muscle of the rat poisoned by plasmocid. Lab Invest 12: 1060–1071
Doroshow JH (1983) Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res 43: 460–472
Hatefi Y, Jurtshuk P, Haavik AG (1961) Studies on the electron transport system. XXXII. Respiratory control in beef heart mitochondria. Arch Biochem Biophys 94: 148–155
Hicks SP (1950) Brain metabolism in vivo. II. The distribution of lesions caused by azide, malononitrile, plasmocid, and dinitrophenol poisoning in rats. Arch Pathol 50: 545–565
Hieda N, Toki Y, Sugiyama S, Ito T, Satake T, Ozawa T (1988) Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes. Cardiovasc Res 22: 219–225
Kambara N, Takagi K, Satake T, Sugiyama S, Ozawa T (1983) Mechanism responsible for endotoxin-induced lung microsomal dysfunction inrats. Lung 161: 361–368
Kato K, Yoshida K, Tsukamoto H, Nobunaga M, Masuya T, Sawada T (1960) Synthesis of p-nitropheny-β-d-glucopyranosiduronic acid and its utilization as a substrate for the assay of β-glucuronidase activity. Chem Pharmacol Bull 8: 239–242
Kondo T, Ogawa Y, Sugiyama S, Ito T, Satake T, Ozawa T (1987) Mechanism of isoproterenol induced myocardial damage. Cardiovasc Res 21: 248–254
Nagai S, Miyazaki Y, Ogawa K, Satake T, Sugiyama S, Ozawa T (1985) The effect of coenzyme Q10 on reperfusion injury in canine myocardium. J Mol Cell Cardiol 17: 873–884
Nagai S, Sugiyama S, Ozawa T (1986) Classification of β-blocking agents by their inhibitory effects on phospholipase activity. Jpn Circ J 50: 238–241
Nakase H (1985) Z-line alteration in plasmocid-induced myopathy. Clin Neurol 25: 796–807
Noto A, Ogawa Y, Mori S, Yoshioka M, Kitakaze T, Hori T, Nakamura M, Miyake T (1983) Simple, rapid spectrophotometry of urinary N-acetyl-β-d-glucosaminidase with use of a new chromogenic substrate. Clin Chem 29: 1713–1716
Ogawa Y, Kondo T, Sugiyama S, Ogawa K, Satake T, Ozawa T (1987) Role of phospholipase in the genesis of doxorubicin induced cardiomyopathy in rats. Cancer Res 47: 1239–1243
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissue by thiobarbituric acid reaction. Anal Biochem 95: 351–358
Pickett WC, Jesse RL, Cohen P (1977) Initiation of phospholipase A2 activity in human platelets by the calcium ion ionophore A23187. Biochim Biophys Acta 486: 209–213
Price HM, Pease DC, Pearson CM (1962) Selective actin filament and Z-band degeneration induced by plasmocid. An electron microscopic study. Lab Invest 11: 549–562
Rona G (1985) Catecholamine cardiotoxicity. J Mol Cell Cardiol 17: 291–306
Ruth RC, Kennett FF, Weglicki WB (1978) A new technique for isolation of particulate lysosomal activity from canine and rat myocardium. J Mol Cell Cardiol 10: 739–751
Sevanian A, Stein RA, Mead JF (1981) Metabolism of epoxidized phosphatidylcholine by phospholipae A2 and epoxide hydrolase. Lipids 16: 781–789
Sevanian A, Muakkassah-Kelly SF, Montestruque S (1983) The influence of phospholipase A2 and glutathione peroxidase on the elimination of membrane lipid peroxides. Arch Biochem Biophys 223: 441–452
Shimomura Y, Sugiyama S, Takamura T, Kondo T, Ozawa T (1986) Quantitative determination of the fatty acid composition of human serum lipids by high-performance liquid chromatography. J Chromatogr Biomed 383: 9–17
Sugiyama S, Ozawa T, Kato T, Suzuki S (1980) Recovery time course of ventricular vulnerability after coronary reperfusion in relation to mitochondrial function in ischemic myocardium. Am Heart J 100: 829–838
Sugiyama S, Miyazaki Y, Kotaka K, Ozawa T (1983) The effects of verapamil on mitochondrial dysfunction associated with coronary reperfusion. Jpn Circ J 47: 830–836
Yasuda M, Fujita T (1977) Effect of lipid peroxidation on phospholipase A2 activity of rat liver mitochondria. Jpn J Pharmacol 27: 429–435
Wallenstein S, Zucker CL, Fleiss JL (1980) Some statistical methods useful in circulation research. Circ Res 47: 1–9
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hieda, N., Sugiyama, S., Ogawa, Y. et al. The role of phospholipase in plasmocid-induced mitochondrial dysfunction in rat hearts. Arch Toxicol 62, 45–48 (1988). https://doi.org/10.1007/BF00316256
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00316256