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DOI QR Code

Pretreatment Hepatoprotective Effect of Regular Aerobic Training Against Hepatic Toxicity Induced by Doxorubicin In Rats

  • Published : 2013.05.30

Abstract

Background: Doxorubicin is an anthracycline antibiotic commonly used to treat a variety of cancers as a most effective antitumor. However, its clinical use is associated with the toxic effects in numerous healthy tissues. Here we investigated the pretreatment effect of regular aerobic exercise on oxidative stress in rats acutely exposed to DOX-induced hepatotoxicity. Materials and Methods: Forty-eight Wistar male rats were randomly divided into 2 groups: control and training. The training protocol included treadmill running between 25 to 54 min/day and 15 to 20m/min, 5 days/week for 6 weeks. At the end of the exercise training protocol, rats from the control and trained groups were again randomly separated into 3 subgroups: DOX10mg/kg, DOX20mg/kg and saline. All treatments were carried 24 h after the last exercise bout and animals were sacrificed 24 h after DOX and saline injections. Results: Administration of DOX (10 and 20 $mg.kg^{-1}$) resulted in imbalance in biomarkers related to oxidants and antioxidants in liver tissue, as compared to control groups. Six weeks of pretreatment training led to a significant increase in nitric oxide (NO), superoxide dismutase (SOD) and glutathione peroxidase (GPX) as compared to the control+DOX 10 mg/kg group. Training before DOX 20 mg/kg administration also led to a significant increase in NO and SOD, and a significant decrease in malondialdehyde (MDA). In addition, there was a significant difference between DOX 10 mg/kg and DOX 20 mg/kg treatments in MDA levels, only. Conclusions: The results of the present study indicate that pretreatment with aerobic exercise induces positive adaptations and has a potential protective effect against doxorubicin (DOX)-induced hepatotoxicity with doses of 10 and 20 mg.kg.

Keywords

References

  1. Ascensao A, Magalhaes J, Soares J, et al (2005). Endurance training attenuates doxorubicin induced cardiac oxidative damage in mice. Int J Cardiol, 100, 451-60. https://doi.org/10.1016/j.ijcard.2004.11.004
  2. Ashrafi J, Dabidi Roshan V (2012). Is Short-term Exercise a Therapeutic Tool for Improvement of Cardioprotection Against DOX-induced Cardiotoxicity? An Experimental Controlled Protocol in Rats. Asian Pac J Cancer Prev, 13, 4025-30. https://doi.org/10.7314/APJCP.2012.13.8.4025
  3. Ashrafi J, Dabidi Roshan V, Mahjoub S (2012). Cardioprotective effects of aerobic regular exercise against doxorubicininduced oxidative stress in rat. AJPP, 6, 2380-8.
  4. Carvalho C, Santos RX, Cardoso S, et al (2009). Doxorubicin: The Good, the Bad and the Ugly Effect. Current Medicinal Chemistry, 16, 3267-85. https://doi.org/10.2174/092986709788803312
  5. Choi J, Park KH, Kim SZ, et al (2013). The ameliorative effects of L-2-oxothiazolidine-4-carboxylate on acetaminopheninduced hepatotoxicity in mice. Molecules, 18, 3467-78. https://doi.org/10.3390/molecules18033467
  6. Dabidi RV, Ranjbar S, Hosseinzadeh M, et al (2012). Left ventricular oxidant and antioxidant markers induced by lifestyle modification in rats exposed to lead acetate. Eur J Sport Sci, 12, 485-490. https://doi.org/10.1080/17461391.2011.573579
  7. Henninger C, Huelsenbeck J, Huelsenbeck S, et al (2012). The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity. Toxicology and Applied Pharmacology, 261, 66-73. https://doi.org/10.1016/j.taap.2012.03.012
  8. Hoene M, Weigert C (2010). The stress response of the liver to physical exercise. Exerc Immunol Rev, 16, 163-83.
  9. Husain K (2002). Exercise conditioning attenuates the hypertensive effects of nitric oxide synthase inhibitor in rat. Molecular and Cellular Biochemistry, 231, 129-37. https://doi.org/10.1023/A:1014416915643
  10. Injac R, Perse M, Obermajer N, et al (2008). Potential hepatoprotective effects of fullerenol C60(OH)24 indoxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials, 29, 3451-60. https://doi.org/10.1016/j.biomaterials.2008.04.048
  11. Kalender Y, Yel M, Kalender S (2005). Doxorubicin hepatotoxicity and hepatic free radical metabolism in rats. The effects of vitamin E and catechin. Toxicology, 209, 39-45. https://doi.org/10.1016/j.tox.2004.12.003
  12. Kavazis A, Smuder A, Kisuk Min, et al (2010). Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol, 299, 1515-24. https://doi.org/10.1152/ajpheart.00585.2010
  13. Korivi M, Hou CW, Huang CY, et al (2012). Ginsenosiderg1 protects the liver against exhaustive exercise-induced oxidative stress in rats. Evid Based Complement Alternat Med, 2012, 932165.
  14. Lima FD, Stamm DN, Della-Pace ID, et al. (2013). Swimming training induces liver mitochondrial adaptations to oxidative stress in rats submitted to repeated exhaustive swimming bouts. PLoS One, 8, 55668. https://doi.org/10.1371/journal.pone.0055668
  15. Ludke AR, Al-Shudiefat AA, Dhingra S, Jassal DS, Singal PK (2009). A concise description of cardioprotective strategies in doxorubicin-induced cardiotoxicity. Can J Physiol Pharmacol, 87, 756-63. https://doi.org/10.1139/Y09-059
  16. Mahmud Z, Bachar S, Qais N (2012). Antioxidant and hepatoprotective activities of ethanolic extracts of leaves of premna esculenta roxb. against carbon tetrachloride-induced liver damage in rats. J Young Pharm, 4, 228-34. https://doi.org/10.4103/0975-1483.104366
  17. Mrzljak A, Kosuta I, Skrtic A, et al. (2013). Drug-induced liver injury associated with noni (Morinda citrifolia) juice and phenobarbital. Case Rep Gastroenterol, 7, 19-24. https://doi.org/10.1159/000343651
  18. Ogawa K, Seta R, Shimizu T, et al (2011). Plasma adenosine triphosphate and heat shock protein 72 concentrations after aerobic and eccentric exercise. Tokyo Metropolitan Institute of Gerontology EIR, 17, 136-49.
  19. Ohkawa H, Ohishi N, Yagi K (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95, 351-8. https://doi.org/10.1016/0003-2697(79)90738-3
  20. Powers SK, Duarte J, Kavazis AN, Talbert EE (2010). Reactive oxygen species are signalling molecules for muscle adaptation. Exp Physiol, 95, 1-9. https://doi.org/10.1113/expphysiol.2009.050526
  21. Radak Z, Chung HY, Naito H, et al (2004). Age-associated increase in oxidative stress and nuclear factor kappaB activation are attenuated in rat liver by regular exercise. FASEB J, 18, 749-50.
  22. Raskovic A, Stilinovic N, Kolarovic J, et al (2011). The protective effects of silymarin against doxorubicin-induced cardiotoxicity and hepatotoxicity in rats. Molecules, 16, 8601-13. https://doi.org/10.3390/molecules16108601
  23. Shirinbayan V, Dabidi Roshan V (2012). Pretreatment effect of running exercise on HSP70 and DOX-induced cardiotoxicity. Asian Pac J Cancer Prev, 13, 5849-55. https://doi.org/10.7314/APJCP.2012.13.11.5849
  24. Siegel R MPH, Naishadham D MA, Jemal A (2012). Cancer statistics. CA, A Cancer J Clinicians, 62, 10-29. https://doi.org/10.3322/caac.20138
  25. Viswanatha SA, Gulliaya S, Thippeswamy A, et al (2012). Cardioprotective effect of curcumin against doxorubicininduced myocardial toxicity in albino rats. Indian J Pharmacol, 44, 73-7. https://doi.org/10.4103/0253-7613.91871
  26. Wonders KY, Hydock DS, Schneider CM, et al (2008). Acute exercise protects against doxorubicin cardiotoxicity. Integr Cancer Ther, 7, 147-54. https://doi.org/10.1177/1534735408322848

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