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Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes

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Abstract

One of the current theories of cardiovascular disease is that it may begin with oxygen radical-induced damages. Extensive studies have been made in different laboratories to elucidate the mechanism of oxidative damages in the presence of added iron salts. However, thosein vitro studies are unlikely to be relevant to thein vivo situation, where in the normal physiological condition most of the iron remains bound with proteins. In the present study we have demonstrated that anin vitro system containing desferrioxamine, a strong iron chelator, superoxide generated by the action of xanthine oxidase on acetaldehyde initiates lipid peroxidation and protein changes in the guinea pig cardiac microsomes. We have further demonstrated that superoxide-initiated lipid peroxidation and protein changes are completely prevented by ascorbic acid. SOD also prevents but catalase, α-tocopherol, glutathione, uric acid, thiourea, mannitol and histidine are without effect. When NADPH is used instead of generated superoxide, the lipid peroxidation and protein changes are exclusively inhibited by ascorbic acid. SOD, catalase and other antioxidants are ineffective. The results obtained with guinea pigs may be extrapolated to humans, because like guinea pigs humans are also incapable of synthesizing ascorbic acid.

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References

  1. Halliwell B, Gutteridge JMC: Role of free radicals and catalytic metal ions in human diseases: An overview. Methods Enzymol 186: 1–85, 1990

    Google Scholar 

  2. Davies KJA, Goldberg AL: Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes. J Biol Chem 262: 8220–8226, 1987

    PubMed  Google Scholar 

  3. Fridovich I: Superoxide radical. An endogenous toxicant. Annu Rev Pharmacol Toxicol 23: 239–257, 1983

    PubMed  Google Scholar 

  4. Aust SD, Roerig DL, Pederson TC: NADPH-dependent lipid peroxidation catalyzed by purified NADPH-cytochrome c reductase from rat liver microsomes. Biochem Biophys Res Commun 47: 1133–1137, 1972

    PubMed  Google Scholar 

  5. Auclair C, Prost DD, Hakin J: Superoxide anion production by liver microsomes from phenobarbital treated rat. Biochem Pharmacol 27: 355–358, 1978

    PubMed  Google Scholar 

  6. Kuthan H, Ullrich V, Eastbrook RW: A quantitative test for superoxide radicals produced in biological system. Biochem J 203: 551–558, 1982

    PubMed  Google Scholar 

  7. Minakami H, Arai H, Nakano M, Sugioka K, Suzuki S, Sotomatsu A: A new and suitable reconstructed system for NADPH-dependent microsomal lipid peroxidation. Biochem Biophys Res Commun 153: 973–978, 1988

    PubMed  Google Scholar 

  8. Som S, Raha C, Chatterjee IB: Ascorbic acid: a scavenger of superoxide radical. Acta Vitaminol Enzymol 5: 243–250, 1983

    PubMed  Google Scholar 

  9. Nandi A, Chatterjee IB: Scavenging of superoxide radical by ascorbic acid. J Biosci 11: 435–441, 1987

    Google Scholar 

  10. Nandi A, Mukhopadhyay C, Chatterjee IB: Scavenging of superoxide radical by ascorbic acid and its role on dopamine β hydroxylase. Int J Toxicol Occup Environ Hlth 1: 43–48, 1991

    Google Scholar 

  11. Nishikimi M: Oxidation of ascorbic acid with superoxide anion generated by the xanthine-xanthine oxidase sytem. Biochem Biophys Res Commun 63: 463–468, 1975

    PubMed  Google Scholar 

  12. Stadtman ER, Oliver CN: Metal catalyzed oxidation of proteins. Physiological consequences. J Biol Chem 266: 2205–2208, 1991

    Google Scholar 

  13. Chakraborty S, Nandi A, Mukhopadhyay CK, Chatterjee IB: Protective role of ascorbic acid against lipid peroxidation and myocarial injury. Mol Cell Biochem 111: 41–47, 1992

    PubMed  Google Scholar 

  14. Singal PK, Kapur N, Dhillon KS, Beamish RE, Dhalla NS: Role of free radical in catecholamine-induced cardiomyopathy. Can J Physiol Pharmacol 60: 1390–1397, 1982

    PubMed  Google Scholar 

  15. Kibata M, Higuchi Y: Serum α-tocopherol, coenzyme Q and thiobarbituric acid — reactive substance in acute myocardial damage and stroke. Ann NY Acad Sci 393: 179–182, 1982

    Google Scholar 

  16. Kudrin AN, Kogan AJ, Koroljiv UV, Nyikolajev SzM, Beszkrovnova NN: The role of lipid peroxidation in the pathogenesis of myocardial infarction and favourable effect of antioxidants sodium selenite and vitamin E. Kardiologia 18: 115, 1978

    Google Scholar 

  17. Das DK, Engelman RM: Mechanism of free radical generation during reperfusion of ischemic myocardium in oxygen radicals: Systemic events and disease processes. Das Esmann (eds) 1989, pp 97–127

  18. McCord JM, Fridovich I: The reaction of cytochrome c by milk xanthine oxidase. J Biol Chem 243: 5753–5757, 1968

    PubMed  Google Scholar 

  19. Battelli MG, DellaCorte E, Stirpe F: Xanthine oxidase type D (dehydrogenase) in the intestine and other organs of the rat. Biochem J 126: 747–749, 1972

    PubMed  Google Scholar 

  20. Das DK, Engelman RM, Otani H, Rousou JA, Breyer RH, Lemeshow S: Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion. Clin Physiol Biochem 4: 187–198, 1986

    PubMed  Google Scholar 

  21. Martonosi A: Sarcoplasmic reticulum IV. Solubilization of microsomal adenosine triphosphate. J Biol Chem 243: 7181, 1968

    Google Scholar 

  22. Aikens J, Dix TA: Perhydroxyl radical initiated lipid peroxidation. J Biol Chem 266: 15091–15098, 1991

    PubMed  Google Scholar 

  23. Esterbauer H, Cheeseman KH: Determination of aldehydic lipid peroxidation products: Malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186: 407–421, 1990

    PubMed  Google Scholar 

  24. Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage Tr. Nature 227: 680–685, 1970

    PubMed  Google Scholar 

  25. Miller DM, Spear NH, Aust SD: Effects of deferrioxamine on iron-catalyzed lipid peroxidation. Arch Biochem Biophys 295: 240–246, 1992

    PubMed  Google Scholar 

  26. Thomas MJ, Mehl KS, Pryor WA: The role of superoxide in xanthine oxidase-induced autooxidation of linoleic acid. J Biol Chem 257: 8343–8347, 1982

    PubMed  Google Scholar 

  27. Sutherland MW, Gebicki JM: A reaction between the superoxide free radical and lipid hydroperoxide in sodium linoleate micelles. Arch Biochem Biophys 214: 1–11, 1982

    PubMed  Google Scholar 

  28. Peters JW, Foote CS: Chemistry of superoxide ion. II. Reaction with hydroperoxides. J Am Chem Soc 98: 873–875, 1976

    Google Scholar 

  29. Thomas MJ, Sutherland MW, Arudi RL, Bielski BHJ: Studies of the reactivity of\(HO_2 /O_2^{\bar \cdot } \) with unsaturated hydroperoxides in ethanolic solutions. Arch Biochem Biophys 233: 772–775, 1984

    Google Scholar 

  30. Gibian MJ, Ungermann T: The unlikelyhood of an electron-transfer (Haber-Weiss) reaction between superoxide and peroxides. J Am Chem Soc 101: 1291–1293, 1979

    Google Scholar 

  31. Stanley JP: Reactions of superoxide with peroxides. J Org Chem 45: 1413–1418, 1980

    Google Scholar 

  32. Davies KJA, Delsignore ME, Lin SW: Protein damage and degradation by oxygen radicals. Modification of amino acids. J Biol Chem 262: 9902–9907, 1987

    PubMed  Google Scholar 

  33. Davies KJA, Delsignore ME: Protein damage and degradation by oxygen radicals. Modification of secondary and tertiary structure. J Biol Chem 262: 9908–9913, 1987

    PubMed  Google Scholar 

  34. Davies KJA, Lin SW, Pacifici RE: Protein damage and degradation by oxygen radicals. Degradation of denatured protein. J Biol Chem 262: 9914–9920, 1987

    PubMed  Google Scholar 

  35. Davies KJA, Goldberg AL: Proteins damaged by oxygen radicals are rapidly degraded in extracts of red blood cells. J Biol Chem 262: 8827–8834, 1987

    Google Scholar 

  36. Davies KJA: Protein damage and degradation by oxygen radicals. General aspects. J Biol Chem 262: 9895–9901, 1987

    PubMed  Google Scholar 

  37. Wefers H, Sies H: The protection by ascorbate and glutathione against microsomal lipid peroxidation is dependent on vitamin E. Eur J Biochem 174: 353–357, 1988

    PubMed  Google Scholar 

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Mukhopadhyay, M., Mukhopadhyay, C.K. & Chatterjee, I.B. Protective effect of ascorbic acid against lipid peroxidation and oxidative damage in cardiac microsomes. Mol Cell Biochem 126, 69–75 (1993). https://doi.org/10.1007/BF01772209

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