Antioxidant Effects of Aerobic Training and Crocin Consumption on Doxorubicin-Induced Testicular Toxicity in Rats
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Abstract
Objective: Doxorubicin (DOX) treatment has been reported to increase the risk of serious toxicity in testis, therefore the aim of the present study was to investigate the antioxidant effects of training and Crocin on doxorubicin-induced testicular toxicity in rats.
Materials and methods: In this experimental study, 42 Wistar rats were randomized into seven groups of six rats, including 1) Control, 2) DOX, 3) DOX + 10 mg/kg/d (day) Crocin, 4) DOX + 50 mg/kg/d Crocin, 5) DOX + high intensity interval training (HIIT), 6) DOX + HIIT with 10 mg/kg/d Crocin and 7) DOX + HIIT with 50 mg/kg/d Crocin. During eight weeks, rats in groups 3, 4, 6, and 7 administered Crocin daily at specific doses by gavage, and groups 5 to 7 performed HIIT(2-8rep2min at 80-110% Vmax) 5 day/w. Also, groups 2 to 7 administered 2 mg/kg/w DOX intraperitoneal. The testes were removed and glutathione peroxidase (GPX), total antioxidant capacity (TAC) and protein carbonyl (PC) were analyzed using ELISA methods, one-way analysis of variance along with Bonferroni’s post hoc test were used for analysis in SPSS (P≤0.05).
Results: The results of the present study showed that doxorubicin induced oxidative stress in testicular tissue by decreasing the level of GPX and TAC and increasing PC level (P≤0.05); TAC and GPX improved in all groups except groups 2 and 5, respectively, and their increase in the group 7 was significantly higher compared to other groups (P≤0.05). Increased PC levels were significantly reduced in the groups 5, 6 and 7.
Conclusion: The increase in antioxidant levels in the concurrent Crocin and training group seems to be dose-dependent, but the oxidative stress in both Crocin and training groups of 10 and 50 mg/kg/d is associated with a decrease, but its modulation in the Crocin consumption group alone depends on the dose.
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3. Olusoji M, Oyeyemi OM, Asenuga ER, Omobowale TO, Ajayi OL, Oyagbemi AA. Protective effect of Gallic acid on doxorubicin‐induced testicular and epididymal toxicity. Andrologia 2017; 49.
4. Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol 2014; 67: 176-86.
5. Matos B, Howl J, Ferreira R, Fardilha M. Exploring the effect of exercise training on testicular function. Eur
J Appl Physiol 2019; 119: 1-8.
6. Georgy GS, Maher OW. Ellagic acid and rosmarinic acid attenuate doxorubicin‐induced testicular injury in rats. J Biochem Mol Toxicol 2017; 31.
7. Mohamed RH, Karam RA, Hagrass HA, Amer MG, Abd El-Haleem MR. Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats. Gene 2015; 561: 107-14.
8. Ahmadian M, Dabidi Roshan V, Leicht AS. Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by doxorubicin in rats. Free Radic Res 2018; 52: 775-82.
9. Magalhães J, Ascensão A, Padrão AI, Aleixo IM, Santos-Alves E, Rocha-Rodrigues S, et al. Can exercise training counteract doxorubicin-induced oxidative damage of testis proteome? Toxicol Lett 2017; 280: 57-69.
10. Hajizadeh Maleki B, Tartibian B. High-intensity interval training modulates male factor infertility through anti-inflammatory and antioxidative mechanisms in infertile men: A randomized controlled trial. Cytokine 2020; 125: 154861.
11. Bartosz G. Total antioxidant capacity. Adv Clin Chem 2003; 37: 219-92.
12. Fedorova M, Bollineni RC, Hoffmann R. Protein carbonylation as a major hallmark of oxidative damage: update of analytical strategies. Mass Spectrom Rev 2014; 33: 79-97.
13. Alihemmati A, Ebadi F, Moghadaszadeh M, Asadi M, Zare P, Badalzadeh R. Effects of high-intensity interval training on the expression of microRNA-499 and
pro-and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats. J Electrocardiol 2019; 55: 9-15.
14. Songstad NT, Kaspersen KH, Hafstad AD, Basnet P, Ytrehus K, Acharya G. Effects of high intensity interval training on pregnant rats, and the placenta, heart and liver of their fetuses. PloS one 2015; 10: e0143095.
15. Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018; 101: 174-80.
16. Adelakun SA, Ogunlade B, Omotoso OD, Oyewo OO. Role of aqueous crude leaf extract of Senecio biafrae combined with zinc on testicular function of adult male Sprague Dawley rats. J Family Reprod Health 2018; 12: 8-17.
17. Jalili C, Roshankhah S, Salahshoor MR, Mohammadi MM. Resveratrol Attenuates Malathion Induced Damage in Some Reproductive Parameters by Decreasing Oxidative Stress and Lipid Peroxidation in Male Rats. J Family Reprod Health 2019; 13: 70-9.
18. Peyravi A, Yazdanpanahi N, Nayeri H, Hosseini SA. The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats. J Food Biochem 2020; 44: e13125.
19. Sefidgar SM, Ahmadi-hamedani M, Jebelli Javan A, Narenji Sani R, Javaheri Vayghan A. Effect of crocin on biochemical parameters, oxidative/antioxidative profiles, sperm characteristics and testicular histopathology in streptozotocin-induced diabetic rats. Avicenna J Phytomed 2019; 9: 347-61.
20. Roshankhah S, Abdolmaleki A, Jalili C, Salahshoor MR. Crocin Reduces Oxidative Stress Produced by Busulfan Administration on Fertility of Male Rats.
J Adv Med Biomed Res 2019; 27: 25-33.
21. Radak Z, Ishihara K, Tekus E, Varga C, Posa A, Balogh L, et al. Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve. Redox Biol 2017; 12: 285-90.
22. Marques-Aleixo I, Santos-Alves E, Mariani D, Rizo-Roca D, Padrão AI, Rocha-Rodrigues S, et al. Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress. Mitochondrion 2015; 20: 22-33.
23. Oharomari LK, Garcia NF, Freitas EC, Jordão Júnior AA, Ovídio PP, Maia AR, et al. Exercise training and taurine supplementation reduce oxidative stress and prevent endothelium dysfunction in rats fed a highly palatable diet. Life Sci 2015; 139: 91-6.
24. Rezaei R, nourshahi M, Bigdeli MR, Khodagholi F, Haghparast A. Effect of eight weeks continues and HIIT exercises on VEGF-A and VEGFR-2 levels in stratum, hippocampus and cortex of wistar rat brain. Physiology of sport and physical activity 2015; 8: 1213-21.
25. Türedi S, Yuluğ E, Alver A, Kutlu Ö, Kahraman C. Effects of resveratrol on doxorubicin induced testicular damage in rats. Exp Toxicol Pathol 2015; 67: 229-35.
26. Rahaiee S, Moini S, Hashemi M, Shojaosadati SA. Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. J Food Sci Technol 2015; 52: 1881-8.
27. Bakhtiary Z, Shahrooz R, Ahmadi A, Soltanalinejad F.
Protective effect of Crocin on DNA damage of sperm and in vitro fertilization (IVF) in adult male mice treated with cyclophosphamide. J Mazandaran Univ Med Sci 2014; 24: 49-59.
28. Sadat Kamali F, Shahrooz R, Najafi G, Razi M. Ameliorative effects of crocin on paraquat-induced oxidative stress in testis of adult mice: An experimental study. Int J Reprod Biomed 2019; 17: 807-18.
29. Zeinali M, Zirak MR, Rezaee SA, Karimi G, Hosseinzadeh H. Immunoregulatory and anti-inflammatory properties of Crocus sativus (Saffron) and its main active constituents: A review. Iran J Basic Med Sci 2019; 22: 334-44.
30. Kalantari A, Saremi A, Shavandi N, Foroutan Nia Nia A. Impact of four week swimming exercise with alpha-tocopherol supplementation on fertility potential in healthy rats. Urol J 2017; 14: 5023-6.
31. Darash K, Ghanbarzadeh M, Nikbakht M. Effect of Simultaneous Eight-Week Exercise and Crocin Usage on the Oxidation and Anti-oxidation Indices of Male Rats’ Testicles Subjected to Apoptosis. Thrita 2019; 8: e90438.
32. Nikbin S, Derakhshideh A, Karimi Jafari S, Mirzahamedani A, Moslehi A, Ourzamani S, et al. Investigating the protective effect of aerobic exercise on oxidative stress and histological damages of testicular tissue associated with chlorpyrifos in male rats. Andrologia 2020; 52: e13468.
33. Husain K, Somani SM. Interaction of exercise training and chronic ethanol ingestion on testicular antioxidant system in rat. J Appl Toxicol 1998; 18: 421-9.
34. Kawamura T, Muraoka I. Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Antioxidants (Basel) 2018; 7: 119.
35. Paes L, Lima D, Matsuura C, de Souza MDG, Cyrino F, Barbosa C, et al. Effects of moderate and high intensity isocaloric aerobic training upon microvascular reactivity and myocardial oxidative stress in rats. PloS one 2020; 15: e0218228.
36. Hajizadeh Maleki B, Tartibian B, Chehrazi M. The effects of three different exercise modalities on markers of male reproduction in healthy subjects: a randomized controlled trial. Reproduction 2017; 153: 157-74.
37. Marques-Aleixo I, Santos-Alves E, Oliveira PJ, Moreira PI, Magalhães J, Ascensão A. The beneficial role of exercise in mitigating doxorubicin-induced Mitochondrionopathy. Biochim Biophys Acta Rev Cancer 2018; 1869: 189-99.
2. Sakai K, Ideta-Otsuka M, Saito H, Hiradate Y, Hara K, Igarashi K, et al. Effects of doxorubicin on sperm DNA methylation in mouse models of testicular toxicity. Biochem Biophys Res Commun 2018; 498: 674-9.
3. Olusoji M, Oyeyemi OM, Asenuga ER, Omobowale TO, Ajayi OL, Oyagbemi AA. Protective effect of Gallic acid on doxorubicin‐induced testicular and epididymal toxicity. Andrologia 2017; 49.
4. Rizk SM, Zaki HF, Mina MA. Propolis attenuates doxorubicin-induced testicular toxicity in rats. Food Chem Toxicol 2014; 67: 176-86.
5. Matos B, Howl J, Ferreira R, Fardilha M. Exploring the effect of exercise training on testicular function. Eur
J Appl Physiol 2019; 119: 1-8.
6. Georgy GS, Maher OW. Ellagic acid and rosmarinic acid attenuate doxorubicin‐induced testicular injury in rats. J Biochem Mol Toxicol 2017; 31.
7. Mohamed RH, Karam RA, Hagrass HA, Amer MG, Abd El-Haleem MR. Anti-apoptotic effect of spermatogonial stem cells on doxorubicin-induced testicular toxicity in rats. Gene 2015; 561: 107-14.
8. Ahmadian M, Dabidi Roshan V, Leicht AS. Age-related effect of aerobic exercise training on antioxidant and oxidative markers in the liver challenged by doxorubicin in rats. Free Radic Res 2018; 52: 775-82.
9. Magalhães J, Ascensão A, Padrão AI, Aleixo IM, Santos-Alves E, Rocha-Rodrigues S, et al. Can exercise training counteract doxorubicin-induced oxidative damage of testis proteome? Toxicol Lett 2017; 280: 57-69.
10. Hajizadeh Maleki B, Tartibian B. High-intensity interval training modulates male factor infertility through anti-inflammatory and antioxidative mechanisms in infertile men: A randomized controlled trial. Cytokine 2020; 125: 154861.
11. Bartosz G. Total antioxidant capacity. Adv Clin Chem 2003; 37: 219-92.
12. Fedorova M, Bollineni RC, Hoffmann R. Protein carbonylation as a major hallmark of oxidative damage: update of analytical strategies. Mass Spectrom Rev 2014; 33: 79-97.
13. Alihemmati A, Ebadi F, Moghadaszadeh M, Asadi M, Zare P, Badalzadeh R. Effects of high-intensity interval training on the expression of microRNA-499 and
pro-and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats. J Electrocardiol 2019; 55: 9-15.
14. Songstad NT, Kaspersen KH, Hafstad AD, Basnet P, Ytrehus K, Acharya G. Effects of high intensity interval training on pregnant rats, and the placenta, heart and liver of their fetuses. PloS one 2015; 10: e0143095.
15. Potnuri AG, Allakonda L, Lahkar M. Crocin attenuates cyclophosphamide induced testicular toxicity by preserving glutathione redox system. Biomed Pharmacother 2018; 101: 174-80.
16. Adelakun SA, Ogunlade B, Omotoso OD, Oyewo OO. Role of aqueous crude leaf extract of Senecio biafrae combined with zinc on testicular function of adult male Sprague Dawley rats. J Family Reprod Health 2018; 12: 8-17.
17. Jalili C, Roshankhah S, Salahshoor MR, Mohammadi MM. Resveratrol Attenuates Malathion Induced Damage in Some Reproductive Parameters by Decreasing Oxidative Stress and Lipid Peroxidation in Male Rats. J Family Reprod Health 2019; 13: 70-9.
18. Peyravi A, Yazdanpanahi N, Nayeri H, Hosseini SA. The effect of endurance training with crocin consumption on the levels of MFN2 and DRP1 gene expression and glucose and insulin indices in the muscle tissue of diabetic rats. J Food Biochem 2020; 44: e13125.
19. Sefidgar SM, Ahmadi-hamedani M, Jebelli Javan A, Narenji Sani R, Javaheri Vayghan A. Effect of crocin on biochemical parameters, oxidative/antioxidative profiles, sperm characteristics and testicular histopathology in streptozotocin-induced diabetic rats. Avicenna J Phytomed 2019; 9: 347-61.
20. Roshankhah S, Abdolmaleki A, Jalili C, Salahshoor MR. Crocin Reduces Oxidative Stress Produced by Busulfan Administration on Fertility of Male Rats.
J Adv Med Biomed Res 2019; 27: 25-33.
21. Radak Z, Ishihara K, Tekus E, Varga C, Posa A, Balogh L, et al. Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve. Redox Biol 2017; 12: 285-90.
22. Marques-Aleixo I, Santos-Alves E, Mariani D, Rizo-Roca D, Padrão AI, Rocha-Rodrigues S, et al. Physical exercise prior and during treatment reduces sub-chronic doxorubicin-induced mitochondrial toxicity and oxidative stress. Mitochondrion 2015; 20: 22-33.
23. Oharomari LK, Garcia NF, Freitas EC, Jordão Júnior AA, Ovídio PP, Maia AR, et al. Exercise training and taurine supplementation reduce oxidative stress and prevent endothelium dysfunction in rats fed a highly palatable diet. Life Sci 2015; 139: 91-6.
24. Rezaei R, nourshahi M, Bigdeli MR, Khodagholi F, Haghparast A. Effect of eight weeks continues and HIIT exercises on VEGF-A and VEGFR-2 levels in stratum, hippocampus and cortex of wistar rat brain. Physiology of sport and physical activity 2015; 8: 1213-21.
25. Türedi S, Yuluğ E, Alver A, Kutlu Ö, Kahraman C. Effects of resveratrol on doxorubicin induced testicular damage in rats. Exp Toxicol Pathol 2015; 67: 229-35.
26. Rahaiee S, Moini S, Hashemi M, Shojaosadati SA. Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. J Food Sci Technol 2015; 52: 1881-8.
27. Bakhtiary Z, Shahrooz R, Ahmadi A, Soltanalinejad F.
Protective effect of Crocin on DNA damage of sperm and in vitro fertilization (IVF) in adult male mice treated with cyclophosphamide. J Mazandaran Univ Med Sci 2014; 24: 49-59.
28. Sadat Kamali F, Shahrooz R, Najafi G, Razi M. Ameliorative effects of crocin on paraquat-induced oxidative stress in testis of adult mice: An experimental study. Int J Reprod Biomed 2019; 17: 807-18.
29. Zeinali M, Zirak MR, Rezaee SA, Karimi G, Hosseinzadeh H. Immunoregulatory and anti-inflammatory properties of Crocus sativus (Saffron) and its main active constituents: A review. Iran J Basic Med Sci 2019; 22: 334-44.
30. Kalantari A, Saremi A, Shavandi N, Foroutan Nia Nia A. Impact of four week swimming exercise with alpha-tocopherol supplementation on fertility potential in healthy rats. Urol J 2017; 14: 5023-6.
31. Darash K, Ghanbarzadeh M, Nikbakht M. Effect of Simultaneous Eight-Week Exercise and Crocin Usage on the Oxidation and Anti-oxidation Indices of Male Rats’ Testicles Subjected to Apoptosis. Thrita 2019; 8: e90438.
32. Nikbin S, Derakhshideh A, Karimi Jafari S, Mirzahamedani A, Moslehi A, Ourzamani S, et al. Investigating the protective effect of aerobic exercise on oxidative stress and histological damages of testicular tissue associated with chlorpyrifos in male rats. Andrologia 2020; 52: e13468.
33. Husain K, Somani SM. Interaction of exercise training and chronic ethanol ingestion on testicular antioxidant system in rat. J Appl Toxicol 1998; 18: 421-9.
34. Kawamura T, Muraoka I. Exercise-induced oxidative stress and the effects of antioxidant intake from a physiological viewpoint. Antioxidants (Basel) 2018; 7: 119.
35. Paes L, Lima D, Matsuura C, de Souza MDG, Cyrino F, Barbosa C, et al. Effects of moderate and high intensity isocaloric aerobic training upon microvascular reactivity and myocardial oxidative stress in rats. PloS one 2020; 15: e0218228.
36. Hajizadeh Maleki B, Tartibian B, Chehrazi M. The effects of three different exercise modalities on markers of male reproduction in healthy subjects: a randomized controlled trial. Reproduction 2017; 153: 157-74.
37. Marques-Aleixo I, Santos-Alves E, Oliveira PJ, Moreira PI, Magalhães J, Ascensão A. The beneficial role of exercise in mitigating doxorubicin-induced Mitochondrionopathy. Biochim Biophys Acta Rev Cancer 2018; 1869: 189-99.
| Files | ||
| Issue | Vol 15, No 1 (March 2021) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v15i1.6075 | |
| Keywords | ||
| Crocin Doxorubicin Exercise Testis | ||
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How to Cite
1.
Davoodi M, Zilaei Bouri S, Dehghan Ghahfarokhi S. Antioxidant Effects of Aerobic Training and Crocin Consumption on Doxorubicin-Induced Testicular Toxicity in Rats. J Family Reprod Health. 2021;15(1):28-37.
