Journal of APPLIED BIOMEDICINE
ISSN 1214-0287 (on-line)
ISSN 1214-021X (printed)

Volume 3 (2005), No 4, p 199-205




Effect of diet supplementation with N-acetylcysteine on leucocyte functions in prematurely aging mice

Noelia Guayerbas, Marta Puerto, Carmen Alvarado, Monica De la Fuente

Address: Monica De la Fuente, Departamento de Fisiologia Animal, Facultad de Ciencias Biologicas, Universidad Complutense, 28040 Madrid, Spain
mondelaf@bio.ucm.es

Received 19th September 2005.
Revised 13th October 2006.
Published online 18th November 2005.

Full text article (pdf)

SUMMARY
According to the free radical theory of aging, oxidative stress plays a key role in the senescent decline of the immune system, and therefore antioxidants may provide an effective therapy in order to protect the immune function against oxidative damage. Accordingly, the purpose of this study was to investigate the favourable effect of a diet supplemented with a glutathione precursor - namely the antioxidant N-acetylcysteine (NAC, 0.1% w/w) - on several functions of the leucocytes from prematurely-aging mice (PAM). In adult PAM, the immune functions studied showed values similar to those of older mice, and worse than those found in adult non prematurely-aging mice (NPAM). A short-term ingestion (4 weeks) of NAC, although unable to influence the NK activity, the IL-2 release or the glutathione content of the peritoneal leucocytes of PAM, resulted in an improvement of other very important leucocyte functions such as the lymphoproliferative response to the mitogen Con A, and IL-1beta and TNFalpha release.

KEY WORDS
antioxidant; glutathione; leucocytes; lymphoproliferation; N-acetylcysteine


REFERENCES
Aspinall R.: Longevity and immune response. Biogerontology 1:273-278, 2000.

Bruunsgaard H, Pedersen M, Pedersen BK: Aging and proinflammatory cytokines, Curr Opin Hematol 8:131-136, 2001.

Chandra RK: Nutrition and immunology: from the clinic to cellular biology and back again. Proc Nutr Soc 58:681-683, 1999.

De la Fuente M: Effects of antioxidants on immune system ageing. Eur J Clin Nutr 56:1-4, 2002.

De la Fuente M. Alvarez P, Alvarado C et al.: A diet supplemented with thiolic antioxidants decreases the oxidative stress in peritoneal leucocytes from prematurely ageing mice. Free Radic Res 37:53, 2003a.

De la Fuente M, Hernanz A, Medina S et al.: Characterization of monoaminergic systems in brain regions of prematurely ageing mice. Neurochem Int 43:165-172, 2003b.

Droge W: Aging-related changes in the thiol/disulfide redox state: implications for the use of thiol antioxidants. Exp Gerontol 37:1333-1345, 2002.

Ferrandez MD, Correa R, Del Rio M, De la Fuente M: Effects in vitro of several antioxidants on the natural killer function of aging mice. Exp Gerontol 34:675-685, 1999.

Franklin RA, Li YM, Arkins S, Kelley KW: Glutathione augments in vitro proliferative responses of lymphocytes to Concanavalin A to a greater degree in old than in young rats. J Nutr 120:1710-1717, 1990.

Golsdstone SD, Hunt NH: Redox regulation of the mitogen-activated protein kinase pathway during lymphocyte activation. Biochim Biophys Acta 1355:353-360, 1997.

Guayerbas N, Sanchez AI, Gamallo A et al.: Mouse performance in an exploratory activity test as a longevity biomarker. Tur-Mari JA and Orellana-Muriana JM (eds), Animal Research Welfare. A partnership, Laboratory Animals Ltd, London 2000, pp. 159-161.

Guayerbas N, Catalan MP, Victor VM et al.: Relation of behavior and macrophage function with the life span in a murine model of premature immunosenescence. Behav Brain Res 134:41-48, 2002a.

Guayerbas N, Puerto M, Victor VM et al.: Leucocyte function and life span in a murine model of premature immunosenescence. Exp Gerontol 37:249-256, 2002b.

Guayerbas N, De la Fuente M: An impairment of phagocytic function is linked to a shorter life span in two strains of prematurely aging mice. Dev Comp Immunol 27:339-350, 2003.

Guevara AG, Guilvard E, Borges MM et al.: N-acetylcysteine and glutathione modulate the behaviour of Trypanosoma cruzi experimental infection. Immunol Lett 71:79-83, 2000.

Hernanz A, Fernandez-Vivancos E et al.: Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci 67:1317-1324, 2000.

Knight JA: Review: free radicals, antioxidants, and the immune system. Annu Clin Lab Sci 30:145-157, 2000.

Medina S, Del Rio M, Hernanz A, De la Fuente M: Age-related changes in the neuropeptide Y effects of murine lymphoproliferation and interleukin-2 production. Peptides 21:1403-1409, 2000.

Pieri C, Moroni F, Recchioni R: Glutathione influences the proliferation as well as the extent of mitochondrial activation in rat splenocytes. Cell Immunol 145:210-217, 1992.

Puerto M, Guayerbas N, Victor VM, De la Fuente M: Effects of the N-acetylcysteine on macrophage and lymphocyte functions in a mouse model of premature ageing. Pharmacol Biochem Behav 73:797-804, 2002.

Sekhon B, Sekhon C, Khan M et al.: N-Acetylcysteine protects against injury in a rat model of focal cerebral ischemia. Brain Res 971:1-8, 2003.

Victor VM, Guayerbas N, Garrote D et al.: Modulation of murine macrophage function by N-acetylcysteine in a model of endotoxic shock. BioFactors 10:347-357, 1999.

Victor VM, Rocha M, De la Fuente M: N-acetylcysteine protects mice from lethal endotoxemia by regulating the redox state of immune cells. Free Radic Res 37:919-929, 2003.

Victor VM, Rocha M, De la Fuente M: Immune cells: free radicals and antioxidants in sepsis. Int Immunopharmacol 4(3):327-347, 2004.

Viora M, Quaranta MG, Straface E et al.: Redox imbalance and immune functions: opposite effects of oxidized low-density lipoproteins and N-acetylcysteine. Immunology 104:431-438, 2001.

Viveros MP, Fernandez B, Guayerbas N, De la Fuente M: Behavioral characterization of a mouse model of premature immunosenescence. J Neuroimmunol 114:80-88, 2001.

Wayne SJ, Rhyme RL, Garry PJ, Goodwin JS: Cell-mediated immunity as a predictor of morbility and mortality in subjects over 60. J Gerontol 45:45-48, 1990.
CITED

De la Fuente M, Hernanz A. The antioxidant N-acetylcysteine in vitro improves several functions of peritoneal leucocytes from old mice approaching their values to those of adult animals. J Appl Biomed. 10: 79-90, 2012.

De la Fuente M, Hernanz A, Viniegra S, Miguel J. Sulfur-containing antioxidants increase in vitro several functions of lymphocytes from mice. Int Immunopharm. 11: 661-669, 2011.

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 Pharmaceut Design. 15: 3003-3026, 2009.

Arranz L, Fernandez C, Rodriguez A, Ribera JM, De La Fuente M. The glutathione precursor N-acetylcysteine improves immune function in postmenopausal women. Free Radical Biol Med. 45: 1252-1262, 2008.

Arranz L, Fernandez C, Rodriguez, A, Ribera JM, De La Fuente M. Changes with ageing in immune cell and plasma glutathione levels. Effect of N-acetylcysteine administration. Rev Espanola de Geriatria y Gerontologia. 42: 96-102, 2007.

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