Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Sport Sciences for Health Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

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

References

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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 167:1–12

    Article  PubMed  PubMed Central  Google Scholar 

  4. Steinbacher P, Eckl P (2015) Impact of oxidative stress on exercising skeletal muscle. Biomolecules 5:356–377

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  7. Ji LL (1993) Antioxidant enzyme response to exercise and aging. Med Sci Sports Exerc 25:225–231

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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 8:18–30

    Article  CAS  PubMed  Google Scholar 

  11. Arnér ESJ (2009) Focus on mammalian thioredoxin reductases—Important selenoproteins with versatile functions. Biochim Biophys Acta Gen Subj 1790:495–526

    Article  Google Scholar 

  12. Nogueira CW, Rocha JBT (2011) Toxicology and pharmacology of selenium: emphasis on synthetic organoselenium compounds. Arch Toxicol 85:1313–1359

    Article  CAS  PubMed  Google Scholar 

  13. Brenneisen P, Steinbrenner H, Sies H (2005) Selenium, oxidative stress, and health aspects. Mol Aspects Med 26:256–267

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  15. Ryan-Harshman M, Aldoori W (2005) The relevance of selenium to immunity, cancer, and infectious/inflammatory diseases. Can J Diet Pract Res 66:98–102

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  19. Nogueira CW, Rocha JBT (2010) Diphenyl diselenide a janus-faced molecule. J Braz Chem, Soc

    Book  Google Scholar 

  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 40:1287–1304

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  23. Paulmier C (1986) Selenium reagents and intermediates in organic synthesis. Pergamon Press. https://doi.org/10.1002/ange.19881000236

    Article  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 65:1575–1582

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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):4623845

    Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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 72:248–254

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

  45. Radak Z, Taylor AW, Ohno H, Goto S (2001) Adaptation to exercise-induced oxidative stress: from muscle to brain. Exerc Immunol Rev 7:90–107

    CAS  PubMed  Google Scholar 

  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

    Article  PubMed  PubMed Central  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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 1863:1066–1077

    Article  CAS  PubMed  Google Scholar 

  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

    Article  CAS  Google Scholar 

  51. Nogueira CW, Zeni G, Rocha JBT (2004) Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev. https://doi.org/10.1021/cr0406559

    Article  PubMed  Google Scholar 

  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 131:2677–2684

    Article  PubMed  Google Scholar 

  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 10:385–390

    CAS  PubMed  Google Scholar 

  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

    Article  CAS  PubMed  Google Scholar 

Download references

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.

Author information

Author notes

  1. Pamela C. Da Rosa and Diane D. Hartmann contributed equally to this manuscript.

Authors and Affiliations

  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 Maria, Brazil

    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, Félix A. A. Soares, Gustavo O. Puntel & Rômulo P. Barcelos

  2. Programa de Pós-graduação em Bioexperimentação (PPGBioexp), Instituto de Ciências Biológicas (ICB), Universidade de Passo Fundo (UPF), BR 285, São José, Passo Fundo, 99052-900, Brazil

    Rômulo P. Barcelos

  3. Instituto Federal Farroupilha (IFF), Santo Ângelo, Brazil

    Nelson R. De Carvalho

Authors
  1. Pamela C. Da Rosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane D. Hartmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sílvio T. Stefanello
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thayanara C. da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martin T. B. Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Micaela B. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José L. Cechella
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Marlon R. Leite
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Nelson R. De Carvalho
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Félix A. A. Soares
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Gustavo O. Puntel
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Rômulo P. Barcelos
    View author publications

    You can also search for this author in PubMed Google Scholar

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.

Corresponding author

Correspondence to Rômulo P. Barcelos.

Ethics declarations

Conflicts of interest

The author declares that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Da Rosa, P.C., Hartmann, D.D., Stefanello, S.T. et al. Diphenyl diselenide blunts swimming training on mitochondrial liver redox adaptation mechanisms of aged animals. Sport Sci Health 16, 281–290 (2020). https://doi.org/10.1007/s11332-019-00603-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11332-019-00603-8

Keywords

Search

Navigation