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Pretreatment Effects of Regular Aerobic Training on the IGF System and Hepatotoxicity Induced by Doxorubicin in Rats

  • Published : 2013.12.31

Abstract

Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats. Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2) $control+DOX_{10}mg{\cdot}kg^{-1}$ (3) $control+DOX_{20}mg{\cdot}kg^{-1}$ (4) training+placebo (5) $training+DOX_{10}mg{\cdot}kg^{-1}$ (6) $training+DOX_{20}mg{\cdot}kg^{-1}$. Hepatotoxicity was induced by DOX with dosages of 10 and 20 $mg{\cdot}kg^{-1}$. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, $DOX_{10}mg{\cdot}kg^{-1}$ and $DOX_{20}mg{\cdot}kg^{-1}$, respectively. Results: Administration of $DOX_{20}mg{\cdot}kg^{-1}$ caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with $10mg{\cdot}kg^{-1}$ and or/ $20mg{\cdot}kg^{-1}$ an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to $C+DOX_{10}$ and $C+DOX_{20}$. Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

References

  1. Aleem E, Elshayeb A, Elhabachi N, et al (2012). Serum IGFBP-3 is a more effective predictor than IGF-1 and IGF-2 for the development of hepatocellular carcinoma in patients with chronic HCV infection. Oncol Lett, 3, 704-12. https://doi.org/10.3892/ol.2011.546
  2. Arikawa AY, Kurzer MS, Thomas W, et al (2010). No effect of exercise on insulin-like growth factor (IGF)-1, insulin and glucose in young women participating in a 16-week randomized controlled trial. Cancer Epidemiol Biomarkers Prev, 19, 2987-90. https://doi.org/10.1158/1055-9965.EPI-10-0828
  3. Ascensao A, Magalhães 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
  4. Ascensao A, Magalhaes J, Soares J, et al (2006). Endurance exercise training attenuates morphological signs of cardiac muscle damage induced by doxorubicin in male mice. Basic Appl Myol, 16, 27-35.
  5. Ascensão A, Oliveira PJ, Magalhaes J (2012). Exercise as a beneficial adjunct therapy during Doxorubicin treatment—Role of mitochondria in cardioprotection. Int J Cardiol, 156, 4-10. https://doi.org/10.1016/j.ijcard.2011.05.060
  6. Cao H, Wang G, Meng L, et al (2012). Association between circulating levels of IGF-1 and IGFBP-3 and lung cancer risk: a meta-analysis. PLoS One, 7, 49884. https://doi.org/10.1371/journal.pone.0049884
  7. Chicco AJ, Schneider CM, Hayward R (2005). Voluntary exercise protects against acute doxorubicin cardiotoxicity in the isolated perfused rat heart. Am J Physiol Regul Integr Comp Physiol, 289, 424-43. https://doi.org/10.1152/ajpregu.00636.2004
  8. Chicco AJ, Hydock DS, Schneider CM, et al (2006), Hayward R. Low-intensity exercise training during doxorubicin treatment protects againstcardiotoxicity, J Appl Physiol, 100, 519-27. https://doi.org/10.1152/japplphysiol.00148.2005
  9. Chicco AJ, Schneider CM, Hayward R(2006). Exercise training attenuates acute doxorubicin-induced cardiac dysfunction. J Cardiovasc Pharmacol, 47, 182-9. https://doi.org/10.1097/01.fjc.0000199682.43448.2d
  10. Dabidi Roshan V, Assali M, HajizadehMoghaddamAk, et al (2011). Exercise training and antioxidants: Effects on rat heart tissue exposed to lead acetate. Int J Toxicol, 30, 190-6. https://doi.org/10.1177/1091581810392809
  11. Dragojevic-Simic VM, Dobric SL, Bokonjic DR, et al (2004). Amifostine protection against doxorubicin cardiotoxicity in rats. Anticancer Drugs, 15, 169-78.
  12. Dziegiel P, Surowiak P, Zabel M (2002). Correlation of histopathological and biochemical appraisal of anthracyclininduced myocardium damage. Folia Histochem Cytobiol, 40, 127-8.
  13. Friedenreich CM, Neilson HK, Woolcott CG, et al (2011). Changes in insulin resistance indicators, IGFs, and adipokines in a year-long trial of aerobic exercise in postmenopausal women. Endocr Relat Cancer, 18, 357-69. https://doi.org/10.1530/ERC-10-0303
  14. Guo YS, Jin GF, Houston CW, et al (1998). Insulin-like growth factor-I promotes multidrug resistance in MCLM colon cancer cells. J Cell Physiol, 175, 141-8. https://doi.org/10.1002/(SICI)1097-4652(199805)175:2<141::AID-JCP3>3.0.CO;2-O
  15. HHydock DS, Lien CY, Schneider CM, et al (2008). Exercise preconditioning protects against doxorubicin induced cardiac dysfunction. Med Sci Sports Exerc, 40, 808-17. https://doi.org/10.1249/MSS.0b013e318163744a
  16. Ibrahim SS, Barakat MA,Helmy HS (2010). Modulating Effect of Carvedilol on Doxorubicin-Induced Cardiomyopathy and Hepatic Damage. J Am Sci, 6, 20-32.
  17. Kalyanaraman B, Joseph J, Kalivendi S, et al (2002). Doxorubicininduced apoptosis: implications in cardiotoxicity. Mol Cell Biochem, 234, 119-24.
  18. Kavazis AN, Smuder AJ, Min K, et al (2010). Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72. Am J Physiol Heart Circ Physiol, 5, 1515-24.
  19. Kelishomi RB, Ejtemaeemehr S, Tavangar SM et al(2008). Morphine is protective against doxorubicin-induced cardiotoxicity in rat. J Appl Toxicol, 243, 96-100. https://doi.org/10.1016/j.tox.2007.09.026
  20. King PD, Perry MC (2001). Hepatotoxicity of chemotherapy. Oncologist, 6, 162-76. https://doi.org/10.1634/theoncologist.6-2-162
  21. Ludke AR, Al-Shudiefat AA, Dhingra S, et al (2009). A concise description of cardioprotective strategies in doxorubicininduced cardiotoxicity. Can J PhysiolPharmacol, 87, 756-63. https://doi.org/10.1139/Y09-059
  22. Sprod LK, Janelsins MC, Palesh OG, et al (2012). Health-related quality of life and biomarkers in breast cancer survivors participating in tai chi chuan. J Cancer Surviv, 6, 146-54. https://doi.org/10.1007/s11764-011-0205-7
  23. Wang G, Zhang J, Liu L et al(2012). Quercetin potentiates doxorubicin mediated antitumor effects against liver cancer throughp53/Bcl-xl. PLoS One, 7, 51764. https://doi.org/10.1371/journal.pone.0051764
  24. Wonders KY, Hydock DS, Greufe S, et al (2009). Endurance exercise training preserves cardiac function in rats receiving doxorubicin and the HER-2 inhibitor GW2974. Cancer Chemother Pharmacol, 64, 1105-13. https://doi.org/10.1007/s00280-009-0967-z
  25. 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
  26. Xu M, Sheng L, Zhu X, et al (2010). Protective effect of tetrandrine on doxorubicin-induced cardiotoxicity in rats. Tumori, 96, 460-4. https://doi.org/10.1177/030089161009600314
  27. Yen HC, Oberley TD, Vichitbandha S, et al (1996). Clair DK. The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. J Clin Invest, 98, 1253-60. https://doi.org/10.1172/JCI118909
  28. Zumkeller W (2001). IGFs and IGFBPs: surrogate markers for diagnosis and surveillance of tumour growth? Mol Pathol, 54, 285-8. https://doi.org/10.1136/mp.54.5.285

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