J Appl Biomed 10:79-90, 2012 | DOI: 10.2478/v10136-012-0005-z
The antioxidant N-acetylcysteine in vitro improves several functions of peritoneal leucocytes from old mice approaching their values to those of adult animals
- 1 Department of Physiology, Faculty of Biology, Complutense University of Madrid, Spain
- 2 Department of Biochemistry, La Paz Hospital, Madrid, Spain
The age-related deterioration of the function of immune cells, or immunosenescence, is based on oxidative stress (an imbalance between the levels of oxidants and antioxidant defences with an increase of the former). Accordingly, the ingestion of a diet supplemented with thiolic antioxidants such as N-acetylcysteine (NAC), a glutathione precursor, by aged subjects improved their leucocyte functions. The aim of the present study was to show if NAC improves in vitro several functions of leucocytes from chronologically old mice and if this antioxidant is able to bring the values of these functions to the levels of those of adult animals. Six concentrations of NAC (in a range from 0.001 mM to 2.5 mM) were investigated on several functions of peritoneal leucocytes from old (78±2 weeks of age) BALB/c mice. These functions were those of the phagocytic process in macrophages, namely: adherence to substrate, directed migration or chemotaxis, phagocytosis of inert particles and superoxide anion levels as a measure of digestion capacity, as well as of the adherence and chemotaxis of lymphocytes. These functions were also studied in peritoneal leucocytes from adult (18±2 weeks of age) mice. The results showed that NAC in vitro improves all the functions studied, especially at the highest concentrations, which had shown impaired values in old mice, approaching those of adult animals. Since the immune functions studied are markers of health and predictors of longevity, the administration to aged subjects of NAC, which shows a direct action in leucocytes, seems to be a good strategy to improve their immune system and, therefore, to reach a healthy longevity.
Keywords: N-acetylcysteine; immunosenescence; macrophages; lymphocytes; mice
Received: September 6, 2011; Revised: November 6, 2011; Published: July 31, 2012 Show citation
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References
- Alonso-Fernández P, De la Fuente M. Role of the immune system in aging and longevity. Curr Aging Sci. 4: 78-100, 2011.
Go to original source...
Go to PubMed...
- Anderson R. Effects of ascorbate on leukocytes: Part II. Effects of ascorbic acid and calcium and sodium ascorbate on neutrophil phagocytosis and post-phagocytic metabolic activity. S Afr Med J. 56: 401-404, 1979.
- Arranz L, Fernández C, Rodríguez A, Ribera JM, De la Fuente M. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radic Biol Med. 45: 1252-1262, 2008.
Go to original source...
Go to PubMed...
- Arranz L, Caamano J, Lord JM, De la Fuente M. Preserved immune functions and controlled leukocyte oxidative stress in naturally long-lived mice: Possible role of nuclear factor-κ B. J Gerontol Biol Sci. 65A: 941-950, 2010.
Go to original source...
Go to PubMed...
- Atalay M, Marnila P, Lilius EM, Hanninen O, Sen CK. Glutathione-dependent modulation of exhausting exercise-induced changes in neutrophil function of rats. Eur J Appl Physiol. 74: 342-347, 1996.
Go to original source...
Go to PubMed...
- Aw D, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology 120: 435-446, 2007.
Go to original source...
Go to PubMed...
- Bendich A. Interaction between antioxidant vitamin C and E and their effect on immune responses. In Miquel J, Quintanilla AT, Weber H (eds.): Handbook of Free Radicals and Antioxidants in Biomedicine. II. CRC press, Boca Raton 1989, pp. 153-160.
- Blanco B, Ferrnández MD, Correa R, Del Rio M, Guaza C, Hernanz A, De la Fuente M. Changes in several functions of murine peritoneal macrophages by N-acetylcysteine and thioproline ingestion. Comparative effect between two strains of mice. BioFactors. 10: 179-185, 1999.
Go to original source...
Go to PubMed...
- Boyden SV. The chemotaxis effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J Exp Med. 115: 453-466, 1962.
Go to original source...
Go to PubMed...
- De Flora S, Izzoti A, D'Agostini F, Cesarone CF. Antioxidant activity and other mechanisms of thiol involved in chemoprevention of mutation and cancer. Am J Med. 91: 122-130, 1991.
Go to original source...
Go to PubMed...
- De la Fuente M. Changes in the macrophage function with aging. Comp Biochem Physiol. 81A: 935-938, 1985.
Go to original source...
Go to PubMed...
- De la Fuente M. Effects of antioxidants on immune system ageing. Eur J Clin Nutr. 56: S5-S8, 2002.
Go to original source...
Go to PubMed...
- De la Fuente M. Role of neuroimmunomodulation in aging. Neuroimmunomodulation. 15: 213-223, 2008.
Go to original source...
Go to PubMed...
- De la Fuente M. Murine models of premature ageing for the study of diet-induced immune changes. Improvement of leukocyte functions in two strains of old prematurely ageing mice by dietary supplementation with sulphur-containing antioxidants. Proc Nutr Soc. 69: 651-659, 2010.
Go to original source...
Go to PubMed...
- De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging. The involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 15: 3003-3026, 2009.
Go to original source...
Go to PubMed...
- De la Fuente M, Victor VM. Antioxidants as modulators of immune function. Immunol Cell Biol. 78: 49-54, 2000.
Go to original source...
Go to PubMed...
- De la Fuente M, Carazo M, Correa R, Del Rio M. Changes in macrophage and lymphocyte functions in guinea-pigs after different amounts of vitamin E ingestion. Brit J Nutr. 84: 25-29, 2000.
Go to original source...
Go to PubMed...
- De la Fuente M, Guayerbas N, Catalán MP, Victor VM, Miquel J. The amount of thiolic antioxidant ingestion needed to improve the immune functions is higher in aged than in adult mice. Free Radic Res. 36: 119-126, 2002.
Go to original source...
Go to PubMed...
- De la Fuente M, Baeza I, Guayerbas N, Puerto M, Castillo C, Salazar V, Ariznavarreta C, F-Tresguerres JA. Changes with aging in several leukocyte functions of male and female rats. Biogerontology. 5: 389-400, 2004a.
Go to original source...
Go to PubMed...
- De la Fuente M, Hernanz A, Guayerbas N, Puerto M, Alvarez P, Alvarado C. Changes with age in peritoneal macrophage functions. Implication of leukocytes in the oxidative stress of senescence. Cell Mol Biol. 50: OL683-OL690, 2004b.
- De la Fuente M, Hernanz A, Vallejo MC. The immune system in the oxidation stress conditions of aging and hypertension. Favorable effects of antioxidants and physical exercise. Antioxid Redox Signal 7: 1356-1366, 2005.
Go to original source...
Go to PubMed...
- De la Fuente M, Hernanz A, Guayerbas N, Victor VM, Arnalich F. Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic Res. 42: 272-280, 2008.
Go to original source...
Go to PubMed...
- De la Fuente M, Cruces J, Hernandez O, Ortega E. Strategies to improve the functions and redox state of the immune system in aged subjects. Curr Pharm Des. 17: 3966-3983, 2011a.
Go to original source...
Go to PubMed...
- De la Fuente M Hernanz A, Viniegra S, Miquel J. Sulfur-containing antioxidants increase in vitro several functions of lymphocytes from mice. Int Immunopharmacol. 11: 661-669, 2011b.
Go to original source...
Go to PubMed...
- Del Rio M, Ruedas G, Medina S, Victor VM, De la Fuente M. Improvement by several antioxidants of macrophage function in vitro. Life Sci. 63: 871-881, 1998.
Go to original source...
Go to PubMed...
- Dodd S, Dean O, Copolov DL, Malhi GS, Berk M. N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert Opin Biol Ther. 8: 1955-1962, 2008.
Go to original source...
- Dröge W. Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol. 37: 1333-1345, 2002.
Go to original source...
Go to PubMed...
- Dröge W. Oxidative stress and ageing: is ageing a cysteine deficiency syndrome? Philos Trans R Soc B. 360: 2355-2372, 2005.
Go to original source...
Go to PubMed...
- Dröge W, Breikreuz R. Glutathione and immune function. Proc Nutr Soc. 59: 595-600, 2000.
Go to original source...
Go to PubMed...
- Gressier B, Cabanis A, Lebegue S, Brunet C, Dine T, Luyckx M, Cazin M, Cazin JC. Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparisons in vitro of some thiol-containing drugs. Methods Find Exp Clin Pharmacol. 16: 9-13, 1994.
Go to PubMed...
- Guayerbas N, Catalán M, Victor VM, Miquel M, De la Fuente M. Relation of behaviour and macrophage function to life span in a murine model of premature immunosenescence. Brain Behav Res. 134: 41-48, 2002a.
Go to original source...
Go to PubMed...
- Guayerbas N, Puerto M, Ferrandez MD, De la Fuente M. A diet supplemented with thiolic antioxidants improves leukocyte function in two strains of prematurely ageing mice. Clin Exp Pharmacol Physiol. 29: 1009-1014, 2002b.
Go to original source...
Go to PubMed...
- Guayerbas N, Puerto M, Alvarez P, De la Fuente M. Improvement of the macrophage functions in premature ageing mice by a diet supplemented with thiolic antioxidants. Cell Mol Biol. 50: OL677-OL681, 2004.
- Guayerbas N, Puerto M, Alvarado C, De la Fuente M. Effect of diet supplementation with N-acetylcysteine on leukocyte functions in prematurely ageing mice. J Appl Biomed. 3: 199-205, 2005.
Go to original source...
- Halliwell B. The wandering of a free radical. Free Radic Biol Med. 46: 531-542, 2009.
Go to original source...
Go to PubMed...
- Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 2: 298-300, 1956.
Go to original source...
Go to PubMed...
- Hernanz A, Collazos ME, De la Fuente M. Effect of age, culture media and lymphocyte presence in ascorbate content of peritoneal macrophages from mice and guinea pigs during phagocytosis. Int Arch Allergy Appl Immunol. 91: 166-170, 1990.
Go to original source...
Go to PubMed...
- Hernanz A, Fernández-Vivancos E, Montiel C, Vázquez JJ, Arnalich F. Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci. 67: 1317-1324, 2000.
Go to original source...
Go to PubMed...
- High KP. Infection as a cause of age-related morbidity and mortality. Ageing Res Rev. 3: 1-14, 2004.
Go to original source...
Go to PubMed...
- Hirokawa J, Sakaue S, Furuya Y, Ishii J, Hasegawa A, Tagami S, Kawakami Y, Sakai M, Nishi S, Nishihira J. Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes. J Biochem. 123: 733-739, 1998.
Go to original source...
Go to PubMed...
- Jariwalla RJ, Harakeh S: Antiviral and immunomodulatory activities of ascorbic acid. Subcell Biochem. 25: 213-231, 1996.
Go to original source...
Go to PubMed...
- Karlsson H, Nava S, Remberger M, Hassan M, Ringden O. Eur J Immunol. 41: 1143-1153, 2011.
Go to original source...
Go to PubMed...
- Knight JA. Review: Free Radicals, Antioxidants, and immune system. Ann Clin Lab Sci. 30: 145-158, 2000.
- Lavie L. Sleep-disordered breathing and cerebrovascular disease: a mechanistic approach. Neurol Clin. 23: 1059-1075, 2005.
Go to original source...
Go to PubMed...
- Millea PJ. N-acetylcysteine: multiple clinical applications. Am Fam Physician. 80: 265-269, 2009.
Go to PubMed...
- Miquel J. An update on the oxygen stress-mitochondrial mutation theory of aging: genetic and evolutionary implications. Exp Gerontol. 33: 113-126, 1998.
Go to original source...
Go to PubMed...
- Miquel J, Economos AC, Fleming J, Johnson JE, Jr. Mitochondrial role in cell aging. Exp Gerontol. 15: 575-591, 1980.
Go to original source...
Go to PubMed...
- Pomaki M, Mota MJ, De la Fuente M, Berger J, Effect of thiolic antioxidants on in vitro mouse peritoneal macrophage functions. Comp Clin Path. 13: 176-181, 2005.
Go to original source...
- Puerto M, Guayerbas N, Victor VM, De la Fuente M. Effects of N-acetylcysteine on macrophage and lymphocyte functions in a mouse model of premature ageing. Pharmacol Biochem Behav. 73: 797-804, 2002.
Go to original source...
Go to PubMed...
- Victor VM, De la Fuente M. N-acetylcysteine improves in vitro the function of macrophages from mice with endotoxin-induced oxidative stress. Free Radic Res. 36: 33-45, 2002.
Go to original source...
Go to PubMed...
- Victor VM, De la Fuente M. Immune cells redox state from mice with endotoxin-induced oxidative stress. Involvement of NF-κB. Free Radic Res. 37: 19-27, 2003.
Go to original source...
Go to PubMed...
- Victor VM, Rocha M, Esplugues JV, De la Fuente M. Role of free radicals in sepsis: Antioxidant therapy. Curr Pharm Des. 11: 3141-3158, 2005.
Go to original source...
Go to PubMed...
- Viña J, Gomez-Cabrera MC, Borras C. Fostering antioxidant defences: up-regulation of antioxidant genes or antioxidant supplementation? Br J Nutr. 98: S36-S40, 2007.
Go to original source...
Go to PubMed...
- Viveros MP, Arranz L, Hernanz A, Miquel J, De la Fuente M. A model of premature ageing in mice based on altered stress-related behavioural response and immunosenescence. Neuroimmunomodulation. 14: 157-162, 2007.
Go to original source...
Go to PubMed...
- Wayne SL, Rhyne RL, Garry PJ, Goodwin JS. Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol. 45: M45-48, 1990.
Go to original source...
Go to PubMed...
- Winterbourn CC. Superoxide as an intracellular radical sink. Free Radic Biol Med. 14: 85-90, 1993.
Go to original source...
Go to PubMed...
- Yoon SO, Yun ChH, Cheng AS. Dose effect of oxidative stress on signal transduction in aging. Mech Ageing Dev. 50: 1-8, 2002.
Go to original source...
Go to PubMed...