Molecular and Cellular Biochemistry

, Volume 387, Issue 1–2, pp 197–205 | Cite as

Antioxidant and antiapoptotic properties of melatonin restore intestinal calcium absorption altered by menadione

  • A. Carpentieri
  • A. Marchionatti
  • V. Areco
  • A. Perez
  • V. Centeno
  • N. Tolosa de Talamoni
Article

Abstract

The intestinal Ca2+ absorption is inhibited by menadione (MEN) through oxidative stress and apoptosis. The aim of this study was to elucidate whether the antioxidant and antiapoptotic properties of melatonin (MEL) could protect the gut against the oxidant MEN. For this purpose, 4-week-old chicks were divided into four groups: (1) controls, (2) treated i.p. with MEN (2.5 μmol/kg of b.w.), (3) treated i.p. with MEL (10 mg/kg of b.w.), and (4) treated with 10 mg MEL/kg of b.w after 2.5 μmol MEN/kg of b.w. Oxidative stress was assessed by determination of glutathione (GSH) and protein carbonyl contents as well as antioxidant enzyme activities. Apoptosis was assayed by the TUNEL technique, protein expression, and activity of caspase 3. The data show that MEL restores the intestinal Ca2+ absorption altered by MEN. In addition, MEL reversed the effects caused by MEN such as decrease in GSH levels, increase in the carbonyl content, alteration in mitochondrial membrane permeability, and enhancement of superoxide dismutase and catalase activities. Apoptosis triggered by MEN in the intestinal cells was arrested by MEL, as indicated by normalization of the mitochondrial membrane permeability, caspase 3 activity, and DNA fragmentation. In conclusion, MEL reverses the inhibition of intestinal Ca 2+ absorption produced by MEN counteracting oxidative stress and apoptosis. These findings suggest that MEL could be a potential drug of choice for the reversal of impaired intestinal Ca 2+ absorption in certain gut disorders that occur with oxidative stress and apoptosis.

Keywords

Melatonin Calcium absorption Apoptosis Oxidative stress Menadione 

References

  1. 1.
    Reiter RJ, Rosales-Corral S, Coto-Montes A et al (2011) The photoperiod, circadian regulation and chronodisruption: the requisite interplay between the suprachiasmatic nuclei and the pineal and gut melatonin. J Physiol Pharmacol 62:269–274PubMedGoogle Scholar
  2. 2.
    Tosini G (2000) Melatonin circadian rhythm in the retina of mammals. Chronobiol Int 17:599–612PubMedCrossRefGoogle Scholar
  3. 3.
    Garbarino-Pico E, Carpentieri AR, Contin MA et al (2004) Retinal ganglion cells are autonomous circadian oscillators synthesizing N-acetylserotonin during the day. J Biol Chem 279:51172–51181PubMedCrossRefGoogle Scholar
  4. 4.
    Bubenik GA (2008) Thirty four years since the discovery of gastrointestinal melatonin. J Physiol Pharmacol 59:33–51PubMedGoogle Scholar
  5. 5.
    Huether G, Poeggeler B, Reimer A, George A (1992) Effect of tryptophan administration on circulating melatonin levels in chicks and rats: evidence for stimulation of melatonin synthesis and release in the gastrointestinal tract. Life Sci 51:945–953PubMedCrossRefGoogle Scholar
  6. 6.
    Bubenik GA (2002) Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 47:2336–2348PubMedCrossRefGoogle Scholar
  7. 7.
    Bubenik GA, Hacker RR, Brown GM, Bartos L (1999) Melatonin concentrations in the luminal fluid, mucosa, and muscularis of the bovine and porcine gastrointestinal tract. J Pineal Res 26:56–63PubMedCrossRefGoogle Scholar
  8. 8.
    Ates B, Yilmaz I, Geckil H et al (2004) Protective role of melatonin given either before ischemia or prior to reperfusion on intestinal ischemia-reperfusion damage. J Pineal Res 37:149–152PubMedCrossRefGoogle Scholar
  9. 9.
    Carpentieri A, Diaz de Barboza G, Areco V et al (2012) New perspectives in melatonin uses. Pharmacol Res 65:437–444PubMedCrossRefGoogle Scholar
  10. 10.
    Motilva V, Garcia-Mauriño S, Talero E, Illanes M (2011) New paradigms in chronic intestinal inflammation and colon cancer: role of melatonin. J Pineal Res 51:44–60PubMedCrossRefGoogle Scholar
  11. 11.
    Perez A, Picotto G, Carpentieri A et al (2008) Minireview on regulation of intestinal calcium absorption. Emphasis on molecular mechanisms of transcellular pathway. Digestion 77:22–34PubMedCrossRefGoogle Scholar
  12. 12.
    Graciani FS, Ximenes VF (2012) 2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone™ therapy. Braz J Med Biol Res 45:701–710PubMedCrossRefGoogle Scholar
  13. 13.
    Hattori M, Morita N, Tsujino Y et al (2001) Vitamins D and K in the treatment of osteoporosis secondary to graft-versus-host disease following bone-marrow transplantation. J Int Med Res 29:381–384PubMedCrossRefGoogle Scholar
  14. 14.
    Marchionatti AM, Diaz de Barboza GE, Centeno VA et al (2003) Effects of a single dose of menadione on the intestinal calcium absorption and associated variables. J Nutr Biochem 14:466–472PubMedCrossRefGoogle Scholar
  15. 15.
    Marchionatti AM, Perez AV, Diaz de Barboza GE et al (2008) Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione. Biochim Biophys Acta 1780:101–107PubMedCrossRefGoogle Scholar
  16. 16.
    Pascua P, Camello-Almaraz C, Camello PJ et al (2011) Melatonin, and to a lesser extent growth hormone, restores colonic smooth muscle physiology in old rats. J Pineal Res 51:405–415PubMedCrossRefGoogle Scholar
  17. 17.
    Almenier HA, Al Menshawy HH, Maher MM, Al Gamal S (2012) Oxidative stress and inflammatory bowel disease. Front Biosci 4:1335–1344Google Scholar
  18. 18.
    Ferretti G, Bacchetti T, Masciangelo S, Saturni L (2012) Celiac disease, inflammation and oxidative damage: a nutrigenetic approach. Nutrients 4:243–257PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Circu ML, Aw TY (2011) Redox biology of the intestine. Free Radic Res 45:1245–1266PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Marchionatti AM, Pacciaroni A, Tolosa de Talamoni NG (2013) Effects of quercetin and menadione on intestinal calcium absorption and the underlying mechanisms. Comp Biochem Physiol A: Mol Integr Physiol 164:215–220CrossRefGoogle Scholar
  21. 21.
    Centeno VA, Díaz de Barboza GE, Marchionatti AM et al (2004) Dietary calcium deficiency increases Ca2+ uptake and Ca2+ extrusion mechanisms in chick enterocytes. Comp Biochem Physiol A: Mol Integr Physiol 139:133–141CrossRefGoogle Scholar
  22. 22.
    Tolosa de Talamoni N, Pereira R, de Bronia DH et al (1985) Phospholipids and sialic acid changes produced by vitamin D3 on intestinal mitochondria. Metabolism 34:1007–1011PubMedCrossRefGoogle Scholar
  23. 23.
    Tolosa de Talamoni N, Marchionatti A, Baudino V, Alisio A (1996) Glutathione plays a role in the chick intestinal calcium absorption. Comp Biochem Physiol 115A:127–132CrossRefGoogle Scholar
  24. 24.
    Beauchamp CO, Fridovich I (1973) Isozymes of superoxide dismutase from wheat germ. Biochim Biophys Acta 317:50–64PubMedCrossRefGoogle Scholar
  25. 25.
    Aebi H (1974) Catalase. In: Bermeyer HU (ed) Methods of enzymatic analysis. Academic Press, New York, pp 673–684CrossRefGoogle Scholar
  26. 26.
    Cheng WH, Valentine BA, Lei XG (1999) High levels of dietary vitamin E do not replace cellular glutathione peroxidase in protecting mice from acute oxidative stress. J Nutr 129:1951–1957PubMedGoogle Scholar
  27. 27.
    Anderson ME (1985) Determination of glutathione and glutathione disulfide in biological samples. Methods Enzymol 113:548–555PubMedCrossRefGoogle Scholar
  28. 28.
    Levine RL, Garland D, Oliver CN et al (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478PubMedCrossRefGoogle Scholar
  29. 29.
    Laemmly UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685CrossRefGoogle Scholar
  30. 30.
    Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci 76:4350–4354PubMedCrossRefGoogle Scholar
  31. 31.
    Garcia-Calvo M, Peterson EP, Leiting B et al (1998) Inhibition of human caspases by peptide-based and macromolecular inhibitors. J Biol Chem 273:32608–32613PubMedCrossRefGoogle Scholar
  32. 32.
    Pastorino JG, Snyder JW, Serroni A et al (1993) Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition. J Biol Chem 268:13791–13798PubMedGoogle Scholar
  33. 33.
    Ashkenazi A, Herbst RS (2008) To kill a tumor cell: the potential of proapoptotic receptor agonists. J Clin Invest 118:1979–1990PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Aherne SA, O’Brien NM (2000) Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 29:507–514PubMedCrossRefGoogle Scholar
  35. 35.
    Maity P, Bindu S, Dey S et al (2009) Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. J Pineal Res 46:314–323PubMedCrossRefGoogle Scholar
  36. 36.
    Tahan G, Gramignoli R, Marongiu F et al (2011) Melatonin expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic-acid-induced colitis in rats. Dig Dis Sci 56:715–720PubMedCrossRefGoogle Scholar
  37. 37.
    Swiderska-Kołacz G, Klusek J, Kołataj A (2006) The effect of melatonin on glutathione and glutathione transferase and glutathione peroxidase activities in the mouse liver and kidney in vivo. Neuro Endocrinol Lett 27:365–368PubMedGoogle Scholar
  38. 38.
    Bhatti JS, Sidhu IP, Bhatti GK (2011) Ameliorative action of melatonin on oxidative damage induced by atrazine toxicity in rat erythrocytes. Mol Cell Biochem 353:139–149PubMedCrossRefGoogle Scholar
  39. 39.
    Lee KM, Lee IC, Kim SH et al (2012) Melatonin attenuates doxorubicin-induced testicular toxicity in rats. Andrologia 44:796–803PubMedCrossRefGoogle Scholar
  40. 40.
    Rodriguez C, Mayo JC, Sainz RM et al (2004) Regulation of antioxidant enzymes: a significant role for melatonin. J Pineal Res 36:1–9PubMedCrossRefGoogle Scholar
  41. 41.
    Tomas-Zapico C, Coto-Montes A (2005) A proposed mechanism to explain the stimulatory effect of melatonin on antioxidative enzymes. J Pineal Res 39:99–104PubMedCrossRefGoogle Scholar
  42. 42.
    Jung KH, Hong SW, Zheng HM et al (2010) Melatonin ameliorates cerulein-induced pancreatitis by the modulation of nuclear erythroid 2-related factor 2 and nuclear factor-kappaB in rats. J Pineal Res 48:239–250PubMedCrossRefGoogle Scholar
  43. 43.
    Marchionatti AM, de Talamoni NT (2010) Effects of menadione on intestinal calcium absorption and antioxidant enzymes. In: Boveris A, Puntarulo S (eds) XII Biennial Meeting of the Society for Free Radical Research International. Medimond SRL, Bologna, pp 349–352Google Scholar
  44. 44.
    Pablos MI, Chuang J, Reiter RJ et al (1995) Time course of the melatonin-induced increase in glutathione peroxidase activity in chick tissues. Biol Signals 4:325–330PubMedCrossRefGoogle Scholar
  45. 45.
    Pablos MI, Agapito MT, Gutierrez R et al (1995) Melatonin stimulates the activity of the detoxifying enzyme glutathione peroxidase in several tissues of chicks. J Pineal Res 19:111–115PubMedCrossRefGoogle Scholar
  46. 46.
    Gerasimenko JV, Gerasimenko OV, Palejwala A et al (2002) Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore. J Cell Sci 115:485–497PubMedGoogle Scholar
  47. 47.
    Wang H, Xu DX, Lv JW et al (2007) Melatonin attenuates lipopolysaccharide (LPS)-induced apoptotic liver damage in D-galactosamine-sensitized mice. Toxicology 237:49–57PubMedCrossRefGoogle Scholar
  48. 48.
    Muñoz-Casares FC, Padillo FJ, Briceño J et al (2006) Melatonin reduces apoptosis and necrosis induced by ischemia/reperfusion injury of the pancreas. J Pineal Res 40:195–203PubMedCrossRefGoogle Scholar
  49. 49.
    Mohseni M, Mihandoost E, Shirazi A et al (2012) Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation-induced apoptosis. Mutat Res 738–739:19–27PubMedCrossRefGoogle Scholar
  50. 50.
    Federico A, Cardaioli E, Da Pozzo P et al (2012) Mitochondria, oxidative stress and neurodegeneration. J Neurol Sci 322:254–262PubMedCrossRefGoogle Scholar
  51. 51.
    Srinivasan V, Spence DW, Pandi-Perumal SR et al (2011) Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimers Dis 2011:326320PubMedCentralPubMedGoogle Scholar
  52. 52.
    Dragicevic N, Delic V, Cao C et al (2012) Caffeine increases mitochondrial function and blocks melatonin signaling to mitochondria in Alzheimer’s mice and cells. Neuropharmacology 63:1368–1379PubMedCrossRefGoogle Scholar
  53. 53.
    Zavodnik IB, Dremza IK, Cheshchevik VT et al (2013) Oxidative damage of rat liver mitochondria during exposure to t-butyl hydroperoxide. Role of Ca2+ ions in oxidative processes. Life Sci 92:1110–1117PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • A. Carpentieri
    • 1
    • 2
  • A. Marchionatti
    • 1
  • V. Areco
    • 1
  • A. Perez
    • 1
  • V. Centeno
    • 1
    • 2
  • N. Tolosa de Talamoni
    • 1
    • 3
  1. 1.Laboratorio de Metabolismo Fosfocálcico y Vitamina D “Dr. Fernando Cañas”, Bioquímica y Biología Molecular, Facultad de Ciencias MédicasINICSA (CONICET-UNC)CórdobaArgentina
  2. 2.Química Biológica, Facultad de OdontologíaUniversidad Nacional de CórdobaCórdobaArgentina
  3. 3.Cátedra de Bioquímica y Biología Molecular, Facultad de Ciencias MédicasUniversidad Nacional de CórdobaCórdobaArgentina

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