N-Acetylcysteine inhibits platelet-monocyte conjugation in patients with type 2 diabetes with depleted intraplatelet glutathione: A randomised controlled trial

Diabetologia

Volumn 55, Issue 11, 2012, Pages 2920-2928

  Treweeke, A T ^a   Winterburn, T J ^a   Mackenzie, I ^a   Barrett, F ^a   Barr, C ^a   Rushworth, G F ^a   Dransfield, I ^b   MacRury, S M ^a   Megson, I L ^a  

^a UNIVERSITY OF THE HIGHLANDS AND ISLANDS   (United Kingdom)

^b UNIVERSITY OF EDINBURGH   (United Kingdom)

Author keywords

Antioxidative treatment; Atherothrombosis; Glutathione; Monocyte; N acetylcysteine; Platelet; Therapeutics; Type 2 diabetes

Indexed keywords

ACETYLCYSTEINE; ACETYLSALICYLIC ACID; GLITAZONE DERIVATIVE; GLUTATHIONE; HEMOGLOBIN A1C; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; METFORMIN; PLACEBO; SULFONYLUREA;

ABSENCE OF SIDE EFFECTS; ADULT; AGED; ARTICLE; BLOOD SAMPLING; CELL LEVEL; CLINICAL ARTICLE; CONTROLLED STUDY; CROSSOVER PROCEDURE; DIABETES CONTROL; DIABETIC PATIENT; DRUG EFFECT; DRUG MECHANISM; FEMALE; HUMAN; HUMAN CELL; MALE; MONOCYTE; NON INSULIN DEPENDENT DIABETES MELLITUS; POSTMENOPAUSE; PRIORITY JOURNAL; PROTEIN DEPLETION; RANDOMIZED CONTROLLED TRIAL; THROMBOCYTE ADHESION; TREATMENT RESPONSE; UNITED KINGDOM;

ACETYLCYSTEINE; ADMINISTRATION, ORAL; AGED; BLOOD PLATELETS; CARDIOVASCULAR DISEASES; CELL COMMUNICATION; CELL-DERIVED MICROPARTICLES; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 2; FEMALE; FREE RADICAL SCAVENGERS; GLUTATHIONE; HUMANS; HYPOGLYCEMIC AGENTS; MALE; MIDDLE AGED; MONOCYTES; PLACEBOS;

EID: 84867490368     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-012-2685-z     Document Type: Article

References (43)

1. Ceriello A, Motz E (2004) Is oxidative stress the pathogenic mechanism underlying insulin resistance, diabetes, and cardiovascular disease? The common soil hypothesis revisited. Arterioscler Thromb Vasc Biol 24:816-823
2. Haidara MA, Yassin HZ, Rateb M, Ammar H, Zorkani MA (2006) Role of oxidative stress in development of cardiovascular complications in diabetes mellitus. Curr Vasc Pharmacol 4:215-227
3. Kaneto H, Katakami N, Kawamori D et al (2007) Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 9:355-366
4. Yu Y, Lyons TJ (2005) A lethal tetrad in diabetes: Hyperglycemia, dyslipidemia, oxidative stress, and endothelial dysfunction. Am J Med Sci 330:227-232
5. Houstis N, Rosen ED, Lander ES (2006) Reactive oxygen species have a causal role inmultiple forms of insulin resistance.Nature 440:944-948
6. Srivastava S, Joshi CS, Sethi PP, Agrawal AK, Srivastava SK, Seth PK (1994) Altered platelet functions in non-insulin-dependent diabetes mellitus (NIDDM). Thromb Res 76:451-461
7. Schaeffer G, Wascher TC, Kostner GM, Graier WF (1999) Alterations in platelet Ca2+ signalling in diabetic patients is due to increased formation of superoxide anions and reduced nitric oxide production. Diabetologia 42:167-176
8. Ferroni P, Basili S, Falco A, Davi G (2004) Platelet activation in type 2 diabetes mellitus. J Thromb Haemost 2:1282-1291
9. Le Brocq M, Leslie SJ, Milliken P, Megson IL (2008) Endothelial dysfunction: From molecular mechanisms to measurement, clinical implications, and therapeutic opportunities. Antioxid Redox Signal 10:1631-1674
10. Belch J, MacCuish A, Campbell I et al (2008) The prevention of progression of arterial disease and diabetes (POPADAD) trial: Factorial randomised placebo-controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ 337:a1840
11. Ogawa H, Nakayama M, Morimoto T et al (2008) Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: A randomized controlled trial. JAMA 300:2134-2141
12. Mazzanti L, Mutus B (1997) Diabetes-induced alterations in platelet metabolism. Clin Biochem 30:509-515
13. Martina V, Bruno GA, Zumpano E, Origlia C, Quaranta L, Pescarmona GP (2001) Administration of glutathione in patients with type 2 diabetes mellitus increases the platelet constitutive nitric oxide synthase activity and reduces PAI-1. J Endocrinol Invest 24:37-41
14. Jones AL (1998)Mechanism of action and value of N-acetylcysteine in the treatment of early and late acetaminophen poisoning: A critical review. J Toxicol Clin Toxicol 36:277-285
15. Fernandez-Fernandez FJ, Sesma P (2011) Acetylcysteine as adjuvant therapy for vasculitis associated with antineutrophil cytoplasmic antibody. J Rheumatol 38:785
16. Lai KY, Ng WY, Osburga Chan PK, Wong KF, Cheng F (2010) High-dose N-acetylcysteine therapy for novel H1N1 influenza pneumonia. Ann Intern Med 152:687-688
17. Virlos IT, Mason J, Schofield D, McCloy RF, Eddleston JM, Siriwardena AK (2003) Intravenous N-acetylcysteine, ascorbic acid and selenium-based anti-oxidant therapy in severe acute pancreatitis. Scand J Gastroenterol 38:1262-1267
18. Watt G, Jongsakul K, Ruangvirayuth R (2002) A pilot study of N-acetylcysteine as adjunctive therapy for severe malaria. QJM 95:285-290
19. Kramer BK, Hoffmann U (2007) Benefit of acetylcysteine for prevention of contrast-induced nephropathy after primary angioplasty. Nat Clin Pract Nephrol 3:10-11
20. Pendyala L, Creaven PJ (1995) Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Canc Epidemiol Biomarkers Prev 4:245-251
21. Aitio ML (2006) N-acetylcysteine-passe-partout or much ado about nothing? Br J Clin Pharmacol 61:5-15
22. Pieper GM, Siebeneich W (1998) Oral administration of the antioxidant, N-acetylcysteine, abrogates diabetes-induced endothelial dysfunction. J Cardiovasc Pharmacol 32:101-105
23. Masha A, Brocato L, Dinatale S, Mascia C, Biasi F, Martina V (2009) N-acetylcysteine is able to reduce the oxidation status and the endothelial activation after a high-glucose content meal in patients with type 2 diabetes mellitus. J Endocrinol Invest 32:352-356
24. Martina V, Masha A, Gigliardi VR et al (2008) Long-term Nacetylcysteine and L-arginine administration reduces endothelial activation and systolic blood pressure in hypertensive patients with type 2 diabetes. Diabetes Care 31:940-944
25. Anfossi G, Russo I, Massucco P, Mattiello L, Trovati M (2003) Platelet resistance to the antiaggregating effect of N-acetyl-L-cysteine in obese, insulin-resistant subjects. Thromb Res 110:39-46
26. Gibson KR, Neilson IL, Barrett F et al (2009) Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: Prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity. J Cardiovasc Pharmacol 54:319-326
27. Gibson KR, Winterburn TJ, Barrett F, Sharma S, Macrury SM, Megson IL (2011) Therapeutic potential of N-acetylcysteine as an antiplatelet agent in patients with type-2 diabetes. Cardiovasc Diabetol 10:43
28. Wilkinson IB, Megson IL, MacCallum T et al (2001) Acute methionine loading does not alter arterial stiffness in humans. J Cardiovasc Pharmacol 37:1-5
29. Shoji T, Koyama H, Fukumoto S et al (2005) Platelet-monocyte aggregates are independently associated with occurrence of carotid plaques in type 2 diabetic patients. J Atheroscler Thromb 12:344-352
30. Wang J, Zhang S, Jin Y, Qin G, Yu L, Zhang J (2007) Elevated levels of platelet-monocyte aggregates and related circulating biomarkers in patients with acute coronary syndrome. Int J Cardiol 115:361-365
31. Zhang SZ, Jin YP, Qin GM, Wang JH (2007) Association of platelet-monocyte aggregates with platelet activation, systemic inflammation, and myocardial injury in patients with non-ST elevation acute coronary syndromes. Clin Cardiol 30:26-31
32. Sarma J, Laan CA, Alam S, Jha A, Fox KA, Dransfield I (2002) Increased platelet binding to circulating monocytes in acute coronary syndromes. Circulation 105:2166-2171
33. da Costa MP, van den Berk N, Ulfman LH, Koenderman L, Hordijk PL, Zwaginga JJ (2004) Platelet-monocyte complexes support monocyte adhesion to endothelium by enhancing secondary tethering and cluster formation. Arterioscler Thromb Vasc Biol 24:193-199
34. Ross R (1993) The pathogenesis of atherosclerosis: A perspective for the 1990s. Nature 362:801-809
35. Bournazos S, Rennie J, Hart SP, Fox KA, Dransfield I (2008) Monocyte functional responsiveness after PSGL-1-mediated platelet adhesion is dependent on platelet activation status. Arterioscler Thromb Vasc Biol 28:1491-1498
36. Braun OO, Johnell M, Varenhorst C et al (2008) Greater reduction of platelet activation markers and platelet-monocyte aggregates by prasugrel compared to clopidogrel in stable coronary artery disease. Thromb Haemost 100:626-633
37. Harding SA, Sarma J, Din JN, Maciocia PM, Newby DE, Fox KA (2006) Clopidogrel reduces platelet-leucocyte aggregation, monocyte activation and RANTES secretion in type 2 diabetes mellitus. Heart 92:1335-1337
38. Ray MJ, Walters DL, Bett JN, Cameron J, Wood P, Aroney CN (2005) Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab. Int J Cardiol 101:249-255
39. Martinez MC, Tual-Chalot S, Leonetti D, Andriantsitohaina R (2011) Microparticles: Targets and tools in cardiovascular disease. Trends Pharmacol Sci 32:659-665
40. Tushuizen ME, Diamant M, Sturk A, Nieuwland R (2011) Cellderived microparticles in the pathogenesis of cardiovascular disease: Friend or foe? Arterioscler Thromb Vasc Biol 31:4-9
41. Amabile N, Rautou PE, Tedgui A, Boulanger CM (2010) Microparticles: Key protagonists in cardiovascular disorders. Semin Thromb Hemost 36:907-916
42. Shantsila E, Kamphuisen PW, Lip GY (2010) Circulating microparticles in cardiovascular disease: Implications for atherogenesis and atherothrombosis. J Thromb Haemost 8:2358-2368
43. Morel O, Toti F, Hugel B et al (2006) Procoagulant microparticles: Disrupting the vascular homeostasis equation? Arterioscler Thromb Vasc Biol 26:2594-2604