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Paper| Volume 40, ISSUE 6, P779-792, December 15, 1985

Effects of aspirin, indomethacin, and sodium salicylate on human erythrocyte membranes as detected with electron spin resonance spectroscopy

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      Abstract

      Electron spin resonance spectroscopy of probed samples was used to determine the structural changes in human erythrocyte membranes prior to and at intervals following ingestion of either 10 grains acetylsalicylic acid, 10 grains sodium salicylate, or 50 mg indomethacin by both male and female subjects. Analysis of erythrocytes from female subjects indicated a time-dependent disordering of the membrane over the eight hour period following aspirin ingestion while the cells of male subjects showed a slight membrane ordering over the same time period. Erythrocytes drawn from females at the beginning of the menstrual cycle showed the greatest amount of membrane disordering at one hour following aspirin ingestion, but by eight hours, the membrane structure had returned to that of control. The time dependent disordering in membrane structure of cells from females in the middle of the menstrual cycle was biphasic. Ingestion of indomethacin induced only slight membrane changes in both male and female subjects over the times examined. Ingestion of sodium salicylate by either men or women did not induce significant changes in erythrocyte membrane order. Washed erythrocytes when mixed with salicylate, aspirin, or indomethacin were either identical to control cells or slightly more ordered. This study suggests that aspirin-induced alterations in membrane structure may depend upon steroid hormone levels.

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      References

        • Crocken J.F.S.
        Commentary: Acetylsalicylic acid or aspirin.
        Can. Med. Assoc. J. 1982; 126: 611-612
        • Waitzman M.B.
        • Kaplan H.
        • Cornelius L.
        • Evatt B.
        Aspirin and prostaglandin effects on diabetic dog blood.
        in: 5th edition. Fed. Proc.40. 1981: 773
        • Preston F.E.
        • Greaves M.
        • Jackson C.A.
        • Stoddard C.J.
        Low-dose aspirin inhibits platelet and venous cyclo-oxygenase in man.
        Thromb. Res. 1982; 27: 477-484
        • Jouve R.
        • Juhan-Vague I.
        • Aillaud M.F.
        • Serment-Jouve M.P.
        • Payan H.
        Comparison of the effects of aspirin and indomethacin on aortic atherogenesis atherosclerosis induced in rabbits.
        Atherosclerosis. 1982; 42: 319-321
        • Spector S.L.
        • Morris H.G.
        • Selmer J.C.
        Clinical responses and serum prostaglandin levels in aspirin idiosyncrasy: Effect of aspirin and a new non-steroidal anti-inflammatory agent.
        Chest. 1981; 80: 676-681
        • Foegh M.L.
        • Winchester J.F.
        • Zmudka M.
        • Helfrich G.B.
        • Ramwell P.W.
        • Schreiner G.E.
        Aspirin inhibition of thromboxane release in thrombosis and renal transplant rejection.
        Lancet Jan. 1982; 2: 48-49
        • Kurokawa H.
        • Sakamoto K.
        Effects of aspirin prednisolone and indomethacin on nephrotoxic serum nephritis in the rat.
        Br. J. Pharmacol. 1982; 75: 87-92
        • Roth G.J.
        • Stanford N.
        • Majerus P.W.
        Acetylation of prostaglandin synthase by aspirin.
        in: 5th edition. Proc. Natl. Acad. Sci. USA.72. 1975: 3073-3076
        • Hamberg M.
        • Svensson J.
        • Wakabayashi T.
        • Samuelsson B.
        Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation.
        in: 5th edition. Proc. Natl. Acad. Sci. USA.71. 1974: 345-349
        • Moncada S.
        • Grylglewski R.
        • Bunting S.
        • Vane J.R.
        An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation.
        Nature. 1976; 263: 663-665
        • Livid M.
        • Del Maschio A.
        • Cerletti C.
        • Degaetano G.
        Indomethacin prevents the long lasting inhibitory effect of aspirin on human platelet cyclo-oxygenase activity.
        Prostaglandins. 1982; 23: 787-796
        • Cerletti C.
        • Lived M.
        • Degaetano G.
        Non-steroidal anti-inflammatory drugs react with two sites on platelet cyclo-cyxygenase: Evidence from “in vivo” drug interaction studies in rats.
        Biochim. Biophys. Acta. 1981; 714: 122-128
        • Stanford N.
        • Roth G.J.
        • Shen T.Y.
        • Majerus P.W.
        Lack of covalent modification of prostaglandin synthetase (cyclo-oxygenase) by indomethacin.
        Prostaglandins. 1977; 13: 669-675
        • Young V.P.
        • Giles A.R.
        • Pater J.
        • Corbett W.E.N.
        Sex differences in bleeding time and blood loss in normal subjects folowing aspirin ingestion.
        Thromb. Res. 1980; 20: 705-709
        • Kelton J.G.
        • Carter C.J.
        • Rosenfeld J.
        • Massicotte-Nolan M.P.
        • Hirsh J.
        Sex-related differences in the efficasy of acetylsalicylic acid (ASA): The absorption of ASA and its effect on collagen-induced thromboxane B2 generation.
        Thromb. Res. 1981; 24: 163-168
        • Buchanan M.R.
        • Rischke J.A.
        • Butt R.
        • Turpie A.G.G.
        • Hirsh J.
        • Rosenfeld J.
        The sex-related differences in aspirin pharmacokinetics in rabbits and man and its relationship to antiplatelet effects.
        Thromb. Res. 1983; 29: 125-139
      1. Final Mortality Statistics, no. 23, 1971, U.S. Department of Health, Education, and Welfare, National Center for Health Statistics, Washington, D.C.

        • Patrignani P.
        • Filabazzi P.
        • Patrano C.
        Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects.
        J. Clin. Invest. 1982; 69: 1366-1372
        • Lewis H.D.
        • Davis J.W.
        • Archibald D.G.
        • Steinke W.E.
        • Smitherman T.C.
        • Doherty J.E.
        • Schaper H.W.
        • Lewinter M.M.
        • Linares E.
        • Pouget J.M.
        • Sabharwal S.C.
        • Chesler E.
        • Demots H.
        Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina.
        N. Engl. J. Med. 1983; 309: 396-403
        • Buchanan M.R.
        • Dejana E.
        • Cazenave J-P.
        • Richardson M.
        • Mustard J.F.
        • Hirsh J.
        Differences in inhibition of PGI2 production by aspirin in rabbit artery and vein segments.
        Thromb. Res. 1980; 20: 447-460
        • Hirsh J.
        Progress Review: The relationship between dose of aspirin, side-effects and antithrombotic effectiveness.
        Stroke. 1985; 16: 1-4
        • Elwood P.C.
        Aspirin in the prevention myocardial infarction: current status.
        Drugs. 1985; 28: 1-5
        • Majerus P.W.
        Arachidonate metabolism in vascular disorders.
        J. Clin. Invest. 1983; 72: 1521-1525
        • Chang W-C.
        • Nakao J.
        • Neichi T.
        • Orimo H.
        • Murota S-J.
        Effects of estrodiol on the metabolism of arachidonic acid by aortas and platelets in rats.
        Biochim. Biophys. Acta. 1981; 664: 291-297
        • Hanley S.P.
        • Cockbill S.R.
        • Bevan J.
        • Heptinstall S.
        Differential inhibition by low-dose aspirin of human veinous prostacyclin synthesis and platelet thromboxane synthesis.
        Lancet May. 1981; 2: 969-971
      2. BURCH, J.W., BAENZIGER, N.L., STEINFORD, N. and MAJERUS, P.W. Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin. Proc. Natl. Acad. Sci. USA 75, 5181–5184.

        • Jaff E.A.
        • Weksler B.B.
        Recovery of endothelial cells prostacyclin production after inhibition by low doses of aspirin.
        J. Clin. Invest. 1979; 63: 532-535
        • Buchanan M.R.
        • Dijana E.
        • Cazenave J-P.
        • Richardson M.
        • Mustard J.F.
        • Hirsh J.
        Differences in inhibition of PGI2 production by aspirin in rabbit artery and vein segments.
        Thromb. Res. 1980; 20: 447-460
        • Buchanan M.R.
        • Dijana E.
        • Gen M.
        • Mustard J.F.
        • Hirsh J.
        Enhanced platelet accumulation on injured carotid arteries following aspirin treatment.
        J. Clin. Invest. 1981; 67: 503-508
        • Goodman L.S.
        • Gilman A.
        5th edition. The pharmacological basis of for transitherapeutics. 305. MacMillan Publ. Co., Inc, New York1975: 326-339
        • Goodman L.S.
        • Gilman A.
        5th edition. The pharmacological basis of for transitherapeutics. 305. MacMillan Publ. Co., Inc, New York1975: 341-343
        • Janoff A.S.
        • Mazorow D.L.
        • Coughlin R.T.
        • Bowdler A.J.
        • Haug A.
        • McGroarty E.J.
        The modification of human erythrocyte membrane stabilizers: An electron-spin resonance study.
        Am. J. Hematol. 1981; 10: 171-179
        • Taylor M.G.
        • Smith I.C.P.
        The conformations of nitroxide-labelled fatty acid probes of membrane structure as studied by 2H-NMR.
        Biochim. Bioph. Acta. 1983; 733: 256-263
        • Worthington R.E.
        • Nakeff A.
        Aspirin inhibits rat megakaryocyte thromboxane synthesis.
        Prostaglandins. 1982; 23: 841-853
        • Dejana E.
        • Cerletti C.
        • De Castellarnau C.
        • Livid M.
        • Galletti F.
        • Latini R.
        • De Gaetano G.
        Salicylate-aspirin interaction in the rat: Evidence that sialicylate accumulating during aspirin administration may protect vascular prostacyclin from aspirin-induced inhibition.
        J. Clin. Invest. 1981; 68: 108-112
        • Rao G.H.R.
        • Johnson G.J.
        • Reddy R.K.
        • White J.G.
        Rapid return of cyclo-oxygenase active platelets in dogs after a single dose of aspirin.
        Prostaglandins. 1981; 22: 761-772
        • Buchanan M.R.
        • Rischke J.A.
        • Hirsh J.
        Asprin inhibits platelet function independent of the acetylation of cyclo-oxygenase.
        Thromb. Res. 1982; 25: 363-373
        • Patrignani P.
        • Filabozzi P.
        • Patrono C.
        Selective cumulative inhibition of platelet thromboxane production by low-dose aspirin in healthy subjects.
        J. Clin. Invest. 1982; 69: 1366-1372
        • Kury P.G.
        • Ramwell P.W.
        • McConnell H.M.
        The effect of prostaglandins E1 and E2 on the human erythrocyte as monitored by spin labels.
        Biochem. Biophys. Res. Commun. 1974; 56: 478-483
        • Rasmussen H.
        • Lake W.
        Prostaglandins and the mammalian erythrocyte.
        in: Silver J. Smith B. Kocsis J.J Prostaglandins in Hematology. Spectrum Publishers, Inc, New York1977: 187-202
        • Taniguchi M.
        • Aikawa M.
        • Sakagawi T.
        Effect of prostaglandin E1 and polyphloretion phosphate on hemolysis of human erythrocytes.
        J. Biochem. (Japan). 1982; 91: 1173-1179
        • Bates G.W.
        • Jackson E.Jr.
        Metabolism of cathechol estrogens by erythrocyte catechol-o methyltransferase.
        Science. 1981; 213: 1145
        • Puca G.A.
        • Sica V.
        Identification of specific high affinity sites for the estradiol receptor in the erythrocyte cytoskeleton.
        Biochem. Biophys. Res. Commun. 1981; 103: 682-689
        • Farley D.B.
        • Van Orden D.E.
        Effect of prostocylcin inhibition by tranylcypromine on uterine 6-keto-PGF1 levels during estrogen hypermia in rats.
        Prostaglandins. 1982; 23: 614-657
        • Farley D.B.
        • Van Orden D.E.
        Effect of prostocylcin inhibition by tranylcypromine on uterine 6-keto-PGF1 levels during estrogen hypermia in rats.
        Prostaglandins. 1982; 23: 614-657
        • Haning Jr., R.V.
        • Choi L.
        • Kiggens A.J.
        • Kuzma D.L.
        Effects of prostaglandins, dibutyral cAMP, LHRH, estrogens, progesterone, and potassium on output of prostaglandin F2α 13, 14-dihydro-15-ketoprostaglandin F2α, HCG, estradiol, and progesterone by placental minces.
        Prostaglandins. 1982; 24: 495-506
        • Thaler-Dao H.
        • Saintot M.
        • Ramonatxo M.
        • Chavis C.
        • Crastegde Paulet A.
        Prostaglandin biosynthesis by the rat uterus during the oestrus cycle, temporal correlation with plasma oestradiol and progesterone concentrations, identifaction of 6-keto PGF1α, as the major metabolite.
        Prostaglandins. 1982; 23: 347-359
        • Mizushima V.
        • Sakai S.
        • Yamaura M.
        Mode of stabilizing action of non-steroid anti-inflammatory drugs on erythrocyte membranes.
        Biochem. Pharmacol. 1970; 19: 227-234
        • Mizushima Y.
        • Sakai S.
        Stabilization of erythrocyte membrane by non-steroid anti-inflammatory drugs.
        J. Pharm. Pharmac. 1969; 21: 327-328
        • Linton E.A.
        • Whitehead S.A.
        Role of arachidonic acid metabolites in the hypothalamic control of ovulation in the rat.
        Biol. of Reprod. 1980; 23: 726-732
        • Reimann F.W.
        Indomethacin but not aspirin increases plasma lithium ion levels.
        Arch. Gen. Psychiatry. 1983; 40: 283-286