Advertisement

Diphenyl diselenide blunts swimming training on mitochondrial liver redox adaptation mechanisms of aged animals

  • Pamela C. Da Rosa
  • Diane D. Hartmann
  • Sílvio T. Stefanello
  • Thayanara C. da Silva
  • Martin T. B. Leite
  • Micaela B. Souza
  • José L. Cechella
  • Marlon R. Leite
  • Nelson R. De Carvalho
  • Félix A. A. Soares
  • Gustavo O. Puntel
  • Rômulo P. BarcelosEmail author
Original Article
  • 3 Downloads

Abstract

Background

Studies about antioxidant supplementation and exercises combined, especially at hepatic liver tissue, are rare and still controversial. In this study, we aimed to evaluate if the association between a recognized antioxidant compound—Diphenyl Diselenide ([(PhSe)2])—and training can reduce homogenate liver and liver mitochondria oxidative stress in old rats.

Methods

Old male Wistar rats were divided into four groups (six animals per group): old-sedentary, old-sedentary [(PhSe)2] supplemented, old-trained, and old-trained [(PhSe)2] supplemented. Trained groups were submitted to swimming training sessions (3% of body weight, 20 min/day during 4 weeks); animals were fed daily with standard feed or standard feed supplemented with 1 ppm of [(PhSe)2] during 4 weeks.

Results

Trained and trained + [(PhSe)2] groups decreased reactive oxygen species (ROS) generation, while only the trained group reduces GSSG production and increased GSH/GSSG ratio when compared to trained + [(PhSe)2]. Mitochondrial ROS production was elevated in control sedentary group, but only swimming training prevented its elevation. However, MnSOD activity was found elevated at trained + [(PhSe)2] rats when compared to the trained and [(PhSe)2] supplementation groups. Mitochondrial Δψm in trained + [(PhSe)2] was decreased compared to trained group, while ratio (III/IV states) was increased when compared to control sedentary.

Conclusions

We conclude that the combination of [(PhSe)2] and swimming training did not manifest synergic effect since it does not prevent the aging-induced hepatic oxidative stress generation, but blunted the induced-exercise adaptations, including at mitochondrial mechanisms.

Keywords

Exercise Supplement Hepatic damage Oxidative stress Aging 

Abbreviations

[(PhSe)2]

Diphenyl diselenide

GSH

Reduced glutathione

GSSG

Oxidized glutathione

MnSOD

Manganese superoxide dismutase

Δψm

Mitochondrial transmembrane electrical potential

H2DCF-DA

Reduced dichlorofluorescein diacetate

DCF

Oxidized dichlorofluorescein

OPT

O-Phthalaldehyde

KCN

Potassium cyanide

Notes

Author contributions

All authors were involved in the development of this manuscript. As the corresponding author, Rômulo P. Barcelos oversaw the complete manuscript development. The study was designed by José L. Cechella; the training was designed and performed by Marlon R. Leite; data were collected and analyzed by Martin T. B. Leite, Micaela B. Souza, Thayanara C. da Silva and Nelson R. De Carvalho; data interpretation and article preparation were undertaken by Pamela C. Da Rosa, Diane D. Hartmann, and Sílvio T. Stefanello; the study conceived and supervisioned, and review of final version by Félix A. A. Soares, Gustavo O. Puntel. All authors have approved the final version of this manuscript.

Funding

This work was supported by Brazilian National Council of Technological and Scientific Development (CNPq), “Coordenação de Aperfeiçoamento de Pessoal de Nível Superior” (CAPES), “Programa de Apoio a Núcleos Emergentes” (PRONEM) MCTI/CNPq [Grant number 472669/2011-7, 475896/2012-2], and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CAPES/PROEX [process number: 23038.005848/2018-31]. FAAS received a fellowship from CNPq. PCR, DDH, STS, JLC, MRL and NRC received a fellowship from CAPES.

Compliance with ethical standards

Conflicts of interest

The author declares that they have no competing interests.

References

  1. 1.
    Alberti KGMM, Zimmet P, Shaw J (2007) International diabetes federation: a consensus on Type 2 diabetes prevention. Diabet Med 24:451–463.  https://doi.org/10.1111/j.1464-5491.2007.02157.x CrossRefPubMedGoogle Scholar
  2. 2.
    Warburton DER, Nicol CW, Bredin SSD (2006) Health benefits of physical activity: the evidence. CMAJ 174:801–809.  https://doi.org/10.1503/cmaj.051351 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Viña J, Sanchis-Gomar F, Martinez-Bello V, Gomez-Cabrera MC (2012) Exercise acts as a drug; The pharmacological benefits of exercise. Br J Pharmacol 167:1–12CrossRefGoogle Scholar
  4. 4.
    Steinbacher P, Eckl P (2015) Impact of oxidative stress on exercising skeletal muscle. Biomolecules 5:356–377CrossRefGoogle Scholar
  5. 5.
    Gomez-Cabrera MC, Domenech E, Viña J (2008) Moderate exercise is an antioxidant: upregulation of antioxidant genes by training. Free Radic Biol Med 44:126–131.  https://doi.org/10.1016/j.freeradbiomed.2007.02.001 CrossRefPubMedGoogle Scholar
  6. 6.
    Rasmussen UF, Krustrup P, Kjær M, Rasmussen HN (2003) Experimental evidence against the mitochondrial theory of aging A study of isolated human skeletal muscle mitochondria. Exp Gerontol 38:877–886.  https://doi.org/10.1016/S0531-5565(03)00092-5 CrossRefPubMedGoogle Scholar
  7. 7.
    Ji LL (1993) Antioxidant enzyme response to exercise and aging. Med Sci Sports Exerc 25:225–231CrossRefGoogle Scholar
  8. 8.
    Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292:C670–C686.  https://doi.org/10.1152/ajpcell.00213.2006 CrossRefPubMedGoogle Scholar
  9. 9.
    Houtkooper RH, Argmann C, Houten SM, Cantó C, Jeninga EH, Andreux PA, Thomas C, Doenlen R, Schoonjans K, Auwerx J (2011) The metabolic footprint of aging in mice. Sci Rep.  https://doi.org/10.1038/srep00134 CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburgh C (2009) Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18–30CrossRefGoogle Scholar
  11. 11.
    Arnér ESJ (2009) Focus on mammalian thioredoxin reductases—Important selenoproteins with versatile functions. Biochim Biophys Acta Gen Subj 1790:495–526CrossRefGoogle Scholar
  12. 12.
    Nogueira CW, Rocha JBT (2011) Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds. Arch Toxicol 85:1313–1359CrossRefGoogle Scholar
  13. 13.
    Brenneisen P, Steinbrenner H, Sies H (2005) Selenium, oxidative stress, and health aspects. Mol Aspects Med 26:256–267CrossRefGoogle Scholar
  14. 14.
    Parnham M, Sies H (2000) Ebselen: prospective therapy for cerebral ischaemia. Expert Opin Investig Drugs 9:607–619.  https://doi.org/10.1517/13543784.9.3.607 CrossRefPubMedGoogle Scholar
  15. 15.
    Ryan-Harshman M, Aldoori W (2005) The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res 66:98–102CrossRefGoogle Scholar
  16. 16.
    Luchese C, Pinton S, Nogueira CW (2009) Brain and lungs of rats are differently affected by cigarette smoke exposure: antioxidant effect of an organoselenium compound. Pharmacol Res 59:194–201.  https://doi.org/10.1016/j.phrs.2008.11.006 CrossRefPubMedGoogle Scholar
  17. 17.
    Prigol M, Schumacher RF, WayneNogueira C, Zeni G (2009) Convulsant effect of diphenyl diselenide in rats and mice and its relationship to plasma levels. Toxicol Lett 189:35–39.  https://doi.org/10.1016/j.toxlet.2009.04.026 CrossRefPubMedGoogle Scholar
  18. 18.
    Carvalho NR, Da Rosa EF, Da Silva MH, Tassi CC, Corte CLD, Carbajo-Pescador S, Mauriz JL, González-Gallego J, Soares FA (2013) New therapeutic approach: diphenyl diselenide reduces mitochondrial dysfunction in acetaminophen-induced acute liver failure. PLoS One.  https://doi.org/10.1371/journal.pone.0081961 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Nogueira CW, Rocha JBT (2010) Diphenyl diselenide a janus-faced molecule. J Braz Chem, SocCrossRefGoogle Scholar
  20. 20.
    Rosa RM, Roesler R, Braga AL, Saffi J, Henriques JAP (2007) Pharmacology and toxicology of diphenyl diselenide in several biological models. Braz J Med Biol Res 40:1287–1304CrossRefGoogle Scholar
  21. 21.
    Leite MR, Cechella JL, Mantovani AC, Duarte MMMF, Nogueira CW, Zeni G (2015) Swimming exercise and diphenyl diselenide-supplemented diet affect the serum levels of pro- and anti-inflammatory cytokines differently depending on the age of rats. Cytokine.  https://doi.org/10.1016/j.cyto.2014.09.006 CrossRefPubMedGoogle Scholar
  22. 22.
    Heck SO, Fulco BCW, Quines CB, Oliveira CES, Leite MR, Cechella JL, Nogueira CW (2017) Combined therapy with swimming exercise and a diet supplemented with diphenyl diselenide is effective against. J Cell Biochem.  https://doi.org/10.1002/jcb.25819 CrossRefPubMedGoogle Scholar
  23. 23.
    Paulmier C (1986) Selenium reagents and intermediates in organic synthesis. Pergamon Press.  https://doi.org/10.1002/ange.19881000236 CrossRefGoogle Scholar
  24. 24.
    de Bem AF, Portella RDL, Colpo E, Duarte MMMF, Frediane A, Taube PS, Nogueira CW, Farina M, da Silva EL, Teixeira Rocha JB (2009) Diphenyl diselenide decreases serum levels of total cholesterol and tissue oxidative stress in cholesterol-fed rabbits. Basic Clin Pharmacol Toxicol 105:17–23.  https://doi.org/10.1111/j.1742-7843.2009.00414.x CrossRefPubMedGoogle Scholar
  25. 25.
    de Bem AF, de Lima Portella R, Perottoni J, Becker E, Bohrer D, Paixão MW, Nogueira CW, Zeni G, Rocha JBT (2006) Changes in biochemical parameters in rabbits blood after oral exposure to diphenyl diselenide for long periods. Chem Biol Interact.  https://doi.org/10.1016/j.cbi.2006.04.005 CrossRefPubMedGoogle Scholar
  26. 26.
    De Bem AF, Portella RDL, Farina M, Perottoni J, Paixão MW, Nogueira CW, Rocha JBT (2007) Low toxicity of diphenyl diselenide in rabbits: a long-term study. Basic Clin Pharmacol Toxicol.  https://doi.org/10.1111/j.1742-7843.2007.00073.x CrossRefPubMedGoogle Scholar
  27. 27.
    Ravi Kiran T, Subramanyam MVV, Asha Devi S (2004) Swim exercise training and adaptations in the antioxidant defense system of myocardium of old rats: relationship to swim intensity and duration. Comp Biochem Physiol B Biochem Mol Biol 137:187–196.  https://doi.org/10.1016/j.cbpc.2003.11.002 CrossRefPubMedGoogle Scholar
  28. 28.
    Bhattacharya SK, Thakar JH, Johnson PL, Shanklin DR (1991) Isolation of skeletal muscle mitochondria from hamsters using an lonic medium containing ethylenediarninetetraacetic acid and nagarse. Anal Biochem 192:344–349.  https://doi.org/10.1016/0003-2697(91)90546-6 CrossRefPubMedGoogle Scholar
  29. 29.
    Kruglov AG, Teplova VV, Saris NEL (2007) The effect of the lipophilic cation lucigenin on mitochondria depends on the site of its reduction. Biochem Pharmacol 74:545–556.  https://doi.org/10.1016/j.bcp.2007.05.012 CrossRefPubMedGoogle Scholar
  30. 30.
    Myhre O, Andersen JM, Aarnes H, Fonnum F (2003) Evaluation of the probes 2′,7′-dichlorofluorescin diacetate, luminol, and lucigenin as indicators of reactive species formation. Biochem Pharmacol 65:1575–1582CrossRefGoogle Scholar
  31. 31.
    García-Ruiz C, Colell A, Marí M, Morales A, Fernández-Checa JC (1997) Direct effect of ceramide on the mitochondrial electron transport chain leads to generation of reactive oxygen species: role of mitochondrial glutathione. J Biol Chem.  https://doi.org/10.1074/jbc.272.17.11369 CrossRefPubMedGoogle Scholar
  32. 32.
    Hissin PJ, Hilf R (1976) A fluorometric method for determination of oxidized and reduced glutathione in tissues. Anal Biochem 74:214–226.  https://doi.org/10.1016/0003-2697(76)90326-2 CrossRefPubMedGoogle Scholar
  33. 33.
    Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247(3170–3175):4623845Google Scholar
  34. 34.
    Geller BL, Winge DR (1984) Subcellular distribution of superoxide dismutases in rat liver. Methods Enzymol 105:105–114.  https://doi.org/10.1016/S0076-6879(84)05014-X CrossRefPubMedGoogle Scholar
  35. 35.
    Åkerman KEO, Wikström MKF (1976) Safranine as a probe of the mitochondrial membrane potential. FEBS Lett 68:191–197.  https://doi.org/10.1016/0014-5793(76)80434-6 CrossRefPubMedGoogle Scholar
  36. 36.
    Da-Silva WS, Gómez-Puyou A, De Gómez-Puyou MT, Moreno-Sanchez R, De Felice FG, De Meis L, Oliveira MF, Galina A (2004) Mitochondrial bound hexokinase activity as a preventive antioxidant defense. Steady-state ADP formation as a regulatory mechanism of membrane potential and reactive oxygen species generation in mitochondria. J Biol Chem 279:39846–39855.  https://doi.org/10.1074/jbc.M403835200 CrossRefPubMedGoogle Scholar
  37. 37.
    Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefGoogle Scholar
  38. 38.
    Ji LL (2015) Redox signaling in skeletal muscle: role of aging and exercise. Adv Physiol Educ 39:352–359.  https://doi.org/10.1152/advan.00106.2014 CrossRefPubMedGoogle Scholar
  39. 39.
    Safwat MH, El-Sawalhi MM, Mausouf MN, Shaheen AA (2014) Ozone ameliorates age-related oxidative stress changes in rat liver and kidney: effects of pre- and post-ageing administration. Biochem 79:450–458.  https://doi.org/10.1134/S0006297914050095 CrossRefGoogle Scholar
  40. 40.
    Kan H, Hu W, Wang Y, Wu W, Yin Y, Liang Y, Wang C, Huang D, Li W (2015) NADPH oxidase-derived production of reactive oxygen species is involved in learning and memory impairments in 16-month-old female rats. Mol Med Rep 12:4546–4553.  https://doi.org/10.3892/mmr.2015.3894 CrossRefPubMedGoogle Scholar
  41. 41.
    Lima FD, Stamm DN, Della-Pace ID, Dobrachinski F, de Carvalho NR, Royes LFF, Soares FA, Rocha JB, González-Gallego J, Bresciani G (2013) Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts. PLoS One.  https://doi.org/10.1371/journal.pone.0055668 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Santos-Alves E, Marques-Aleixo I, Coxito P, Balça MM, Rizo-Roca D, Rocha-Rodrigues S, Martins S, Torrella JR, Oliveira PJ, Moreno AJ, Magalhães J, Ascensão A (2014) Exercise mitigates diclofenac-induced liver mitochondrial dysfunction. Eur J Clin Invest 44:668–677.  https://doi.org/10.1111/eci.12285 CrossRefPubMedGoogle Scholar
  43. 43.
    Barcelos RP, Souza MA, Amaral GP, Stefanello ST, Bresciani G, Fighera MR, Soares FAA, Barbosa NV (2014) Caffeine supplementation modulates oxidative stress markers in the liver of trained rats. Life Sci 96:40–45.  https://doi.org/10.1016/j.lfs.2013.12.002 CrossRefPubMedGoogle Scholar
  44. 44.
    Radák Z, Chung HY, Naito H, Takahashi R, Jung KJ, Kim HJ, Goto S (2004) Age-associated increase in oxidative stress and nuclear factor kappaB activation are attenuated in rat liver by regular exercise. FASEB J 18:749–750.  https://doi.org/10.1096/fj.03-0509fje CrossRefPubMedGoogle Scholar
  45. 45.
    Radak Z, Taylor AW, Ohno H, Goto S (2001) Adaptation to exercise-induced oxidative stress: from muscle to brain. Exerc Immunol Rev 7:90–107PubMedGoogle Scholar
  46. 46.
    Merry TL, Ristow M (2016) Do antioxidant supplements interfere with skeletal muscle adaptation to exercise training? J Physiol.  https://doi.org/10.1113/JP270654 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Barcelos RP, Bresciani G, Rodriguez-Miguelez P, Cuevas MJ, Soares FAA, Barbosa NV, González-Gallego J (2016) Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver. Life Sci.  https://doi.org/10.1016/j.lfs.2016.02.006 CrossRefPubMedGoogle Scholar
  48. 48.
    Puntel RL, Roos DH, Folmer V, Nogueira CW, Galina A, Aschner M, Rocha JBT (2010) Mitochondrial dysfunction induced by different organochalchogens is mediated by thiol oxidation and is not dependent of the classical mitochondrial permeability transition pore opening. Toxicol Sci 117:133–143.  https://doi.org/10.1093/toxsci/kfq185 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Bhatti JS, Bhatti GK, Reddy PH (2017) Mitochondrial dysfunction and oxidative stress in metabolic disorders—a step towards mitochondria based therapeutic strategies. Biochim Biophys Acta Mol Basis Dis 1863:1066–1077CrossRefGoogle Scholar
  50. 50.
    Puntel RL, Roos DH, Seeger RL, Rocha JBT (2013) Mitochondrial electron transfer chain complexes inhibition by different organochalcogens. Toxicol Vitr 27:59–70.  https://doi.org/10.1016/j.tiv.2012.10.011 CrossRefGoogle Scholar
  51. 51.
    Nogueira CW, Zeni G, Rocha JBT (2004) Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev.  https://doi.org/10.1021/cr0406559 CrossRefPubMedGoogle Scholar
  52. 52.
    de Jong N, Gibson RS, Thomson CD, Ferguson EL, McKenzie JE, Green TJ, Horwath CC (2001) Selenium and zinc status are suboptimal in a sample of older New Zealand women in a community-based study. J Nutr 131:2677–2684CrossRefGoogle Scholar
  53. 53.
    Shen CL, Song W, Pence BC (2001) Interactions of selenium compounds with other antioxidants in DNA damage and apoptosis in human normal keratinocytes. Cancer Epidemiol Biomarkers Prev 10:385–390PubMedGoogle Scholar
  54. 54.
    Morin D, Zini R, Ligeret H, Neckameyer W, Labidalle S, Tillement JP (2003) Dual effect of ebselen on mitochondrial permeability transition. Biochem Pharmacol 65:1643–1651.  https://doi.org/10.1016/S0006-2952(03)00114-X CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  • Pamela C. Da Rosa
    • 1
  • Diane D. Hartmann
    • 1
  • Sílvio T. Stefanello
    • 1
  • Thayanara C. da Silva
    • 1
  • Martin T. B. Leite
    • 1
  • Micaela B. Souza
    • 1
  • José L. Cechella
    • 1
  • Marlon R. Leite
    • 1
  • Nelson R. De Carvalho
    • 3
  • Félix A. A. Soares
    • 1
  • Gustavo O. Puntel
    • 1
  • Rômulo P. Barcelos
    • 1
    • 2
    Email author
  1. 1.Programa de Pós-graduação em Ciências Biológicas: Bioquímica Toxicológica (PPGBTox), Centro de Ciências Naturais e Exatas (CCNE)Universidade Federal de Santa Maria (UFSM)Santa MariaBrazil
  2. 2.Programa de Pós-graduação em Bioexperimentação (PPGBioexp), Instituto de Ciências Biológicas (ICB)Universidade de Passo Fundo (UPF)Passo FundoBrazil
  3. 3.Instituto Federal Farroupilha (IFF)Santo ÂngeloBrazil

Personalised recommendations