Abstract
Both melatonin (MEL) and zinc (Zn) are considered beneficial for anti-immunosenescence. MEL’s effects on immune functions are partly attributed to an interaction with Zn. However, the augmentation of or interference with MEL’s effects by coadministration of Zn remains unclear. In this study, adult older mice received either MEL (10 µg/mL), Zn (22 µg/mL), MEL+Zn, or null supplementation from drinking water for 3 mo. The results showed that treated mice, irrespective of the type of added chemicals, had higher body-weight gain and body-fat content than control mice. MEL- and Zn-treated mice also had increased serum free fatty acid levels. In addition, the MEL group had decreased serum NOX (nitrite+nitrate) values. Serum tumor necrosis factor-alpha levels were increased, although nonsignificantly, in mice that received either MEL or Zn supplementation. However, the differences described were not retained in the mice that received MEL+Zn treatment. We conclude that a high-dose Zn coadministration might exert negative influences on MEL’s regulatory effects, at least on nitric oxide production.
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G. L. M. Maestroni, The immunoneuroendocrine role of melatonin,J. Pineal Res. 14, 1–10 (1993).
W. Pierpaoli, The pineal gland as ontogenetic scanner of reproduction, immunity, and aging,Ann. NY Acad. Sci. 719, 46–49 (1994).
R. J. Reiter, R. C. Carneiro, and C. S. Oh, Melatonin in relation to cellular antioxidative defense mechanisms,Horm. Metab. Res. 29, 363–372 (1997).
S. Garcia-Maurino, M. G. Gonzalez-Haba, J. R. Calvo, M. Rafii-El-Idrissi, V. SanchezMargalet, R. Goberna, et al., Melatonin enhances IL-2, IL-6, and IFN-gamma production by human circulating CD4+ cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes,J. Immunol. 159, 574–581 (1997).
E. Gilad, H. E. Wong, B. Zingarelli, L. Virag, M. O’Connor, A. L. Salzman, et al, Melatonin inhibits expression of the inducible isoform of nitric oxide synthase in murine macrophages: role of inhibition of NFkB activation,FASEB J. 12, 685–693 (1998).
R. J. Reiter, Melatonin in the context of the free radical theory of aging,Ann. NY Acad. Sci. 786, 362–378 (1996).
M. K. Hambidge, C. E. Casey, and N. F. Krebs, Zinc, inTrace Elements in Human and Animal Nutrition, Vol. 2, 5th ed., W. Mertz, ed., Academic, New York, pp. 1–137 (1986).
J. Duchetateu, G. Delespesse, R. Vrijen, and H. Coolet, Beneficial effects of oral zinc supplementation on the immune response of old people,Am. J. Med. 70, 1001–1004 (1981).
E. Mocchegiani, D. Bulian, L. Santarelli, A. Tibaldi, W. Pierpaoli, and N. Fabris, The zinc-melatonin interrelationship: a working hypothesis,Ann. NY Acad. Sci. 719, 298–307 (1994).
E. Mocchegiani, D. Bulian, L. Santarelli, A. Tibaldi, M. Muzzioli, W. Pierpaoli, et al., The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice,J. Neuroimmunol. 53, 189–201 (1994).
E. Mocchegiani, D. Bulian, L. Santarelli, A. Tibaldi, M. Muzzioli, V. Lesnikov, et al., The zinc pool is involved in the immune-reconstituting effect of melatonin in pinealectomized mice,J. Pharm. Exp. Ther. 277, 1200–1208 (1996).
S. Le-Gouic, P. Delagrange, C. Atgie, M. Nibbelink, N. Hanoun, L. Casteilla, et al., Effects of both a melatonin agonist and antagonist on seasonal changes in body mass and energy intake in the garden dormouse,Int. J. Obesity 20, 661–667 (1996).
M. D. Chen, P. Y. Lin, and W. H. Sheu, Zinc status in plasma of obese individuals during glucose administration,Biol. Trace Element Res. 60, 123–129 (1997).
M. D. Chen, S. J. Liou, P. Y. Lin, V. C. Yang, P. S. Alexander, and W. H. Lin, Effects of zinc supplementation on the plasma glucose level and insulin activity in genetically obese (ob/ob) mice,Biol. Trace Element Res. 61, 303–311 (1998).
A. Persechini, K. McMillan, and B. S. S. Masters, Inhibition of nitric oxide synthase activity by Zn2+ ion,Biochemistry 34, 15,091–15,095 (1995).
P. L. Kimmel, T. M. Phillips, S. Q. Lew, and C. B. Langman, Zinc modulates mononuclear cellular calcitriol metabolism in peritoneal dialysis patients,Kidney Int. 49, 1407–1412 (1996).
K. J. Tracey, The acute and chronic pathophysiologic effects of TNF: mediation of septic shock and wasting (cachexia), inTumor Necrosis Factors: The Molecules and Their Emerging Role in Medicine, B. Beutler, ed., Raven, New York, pp. 255–273 (1992).
G. S. Hotamisligil and B. M. Spiegelman, Tumor necrosis factor-α: a key component of the obesity-diabetes link,Diabetes 43, 1271–1278 (1994).
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Chen, MD., Lin, PY. & Sheu, W.HH. Zinc coadministration attenuates melatonin’s effect on nitric oxide production in mice. Biol Trace Elem Res 69, 261–268 (1999). https://doi.org/10.1007/BF02783878
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DOI: https://doi.org/10.1007/BF02783878