Clinical and Experimental Reproductive Medicine

  • 제47권3호
  • /
  • Pages.155-160
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  • 2020
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  • 2233-8233(pISSN)
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  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
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Effect of L-carnitine on the expression of the apoptotic genes Bcl-2 and Bax

  • Vardiyan, Reyhane (Department of Biology and Anatomy, Shahid Sadoughi University of Medical Sciences) ;
  • Ezati, Daniyal (Department of Biology and Anatomy, Shahid Sadoughi University of Medical Sciences) ;
  • Anvari, Morteza (Research and Clinical Center for Infertility, Shahid Sadoughi University of Medical Sciences) ;
  • Ghasemi, Nasrin (Department of Biology and Anatomy, Shahid Sadoughi University of Medical Sciences) ;
  • Talebi, Alireza (Department of Biology and Anatomy, Shahid Sadoughi University of Medical Sciences)
  • 투고 : 2019.11.24
  • 심사 : 2020.04.03
  • 발행 : 2020.09.30
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초록

Objective: The genes Bcl-2 and Bax play important roles in apoptosis. Many studies have shown that formalin has a strong deleterious effect on male fertility and can induce apoptosis. L-carnitine has been reported to potentially reverse the negative effects of formalin, leading to improved spermatogenesis. In this study, we examined the levels of expression of Bcl-2 and Bax in mice treated with formalin and L-carnitine. Methods: Thirty adult BALB/c mice were categorized into three groups. The mice in the control group (n = 10) were not injected with any substance. The mice in the second group (n = 10) received 10 mg/kg of formalin daily via an intraperitoneal injection, while those in the final group (n = 10) were intraperitoneally injected daily with a dose of 10 mg/kg of formalin and 100 mg/kg of L-carnitine. All mice were kept in isolated cages for 31 days. Results: The expression of Bax was significantly higher in the formalin-treated mice than in the mice of the control group, while the expression of Bcl-2 was significantly lower in the formalin-treated mice than in the control mice. Additionally, relative to control mice, Bcl-2 expression increased and Bax expression decreased in the mice administered both formalin and L-carnitine. Conclusion: In this study, L-carnitine was shown to augment Bcl-2 expression and to reduce Bax expression, indicating that this compound may inhibit apoptosis. Due to its positive effects, L-carnitine can be used as a prophylactic treatment for people who routinely come into direct contact with formalin as an occupational hazard.

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참고문헌

  1. Babakhanzadeh E, Khodadadian A, Rostami S, Alipourfard I, Aghaei M, Nazari M, et al. Testicular expression of TDRD1, TDRD5, TDRD9 and TDRD12 in azoospermia. BMC Med Genet 2020;21:33. https://doi.org/10.1186/s12881-020-0970-0
  2. Babakhanzadeh E, Nazari M, Ghasemifar S, Khodadadian A. Some of the factors involved in male infertility: a prospective review. Int J Gen Med 2020;13:29-41. https://doi.org/10.2147/ijgm.s241099
  3. Henriques MC, Loureiro S, Fardilha M, Herdeiro MT. Exposure to mercury and human reproductive health: a systematic review. Reprod Toxicol 2019;85:93-103. https://doi.org/10.1016/j.reprotox.2019.02.012
  4. Schatten H, Rawe VY, Sun QY. Cytoskeletal architecture of human oocytes with a focus on centrosomes and their significant role in fertilization. In Vitro Fertilization. Berlin: Springer; 2019.
  5. Gnanadeepam JC, Rajavel AT, Eswaran SE, Thiagarajan PR. Histological changes in testis of wistar albino rats following formaldehyde exposure by inhalation. J Clin Diagno Res 2018;12.
  6. Tajaddini S, Ebrahimi S, Behnam B, Bakhtiyari M, Joghataei MT, Abbasi M, et al. Antioxidant effect of manganese on the testis structure and sperm parameters of formalin-treated mice. Andrologia 2014;46:246-53. https://doi.org/10.1111/and.12069
  7. El-Hak HN. The protective effects of panax ginseng extract on fertility of albino rats treated with formaldehyde vapours. Egyptian J Zoology 2017:221-38.
  8. Klocke S, Bundgen N, Koster F, Eichenlaub-Ritter U, Griesinger G. Slow-freezing versus vitrification for human ovarian tissue cryopreservation. Arch Gynecol Obstet 2015;291:419-26. https://doi.org/10.1007/s00404-014-3390-6
  9. Naghdi M, Maghbool M, Seifalah-Zade M, Mahaldashtian M, Makoolati Z, Kouhpayeh SA, et al. Effects of common fig (Ficus carica) leaf extracts on sperm parameters and testis of mice intoxicated with formaldehyde. Evid Based Complement Alternat Med 2016; 2016:2539127.
  10. Vosoughi S, Khavanin A, Salehnia M, Asilian Mahabadi H, Shahverdi A, Esmaeili V. Adverse effects of formaldehyde vapor on mouse sperm parameters and testicular tissue. Int J Fertil Steril 2013;6:250-67.
  11. Agarwal A, Saleh RA. Role of oxidants in male infertility: rationale, significance, and treatment. Urol Clin North Am 2002;29:817-27. https://doi.org/10.1016/S0094-0143(02)00081-2
  12. Agarwal A, Sharma RK, Nallella KP, Thomas AJ Jr, Alvarez JG, Sikka SC. Reactive oxygen species as an independent marker of male factor infertility. Fertil Steril 2006;86:878-85. https://doi.org/10.1016/j.fertnstert.2006.02.111
  13. Makker K, Agarwal A, Sharma R. Oxidative stress & male infertility. Indian J Med Res 2009;129:357-67.
  14. Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pac J Clin Nutr 2007;16 Suppl 1:383-90.
  15. Cavallini G, Ferraretti AP, Gianaroli L, Biagiotti G, Vitali G. Cinnoxicam and L-carnitine/acetyl-L-carnitine treatment for idiopathic and varicocele-associated oligoasthenospermia. J Androl 2004;25:761-70. https://doi.org/10.1002/j.1939-4640.2004.tb02853.x
  16. Yu J, Ye J, Liu X, Han Y, Wang C. Protective effect of L-carnitine against H(2)O(2)-induced neurotoxicity in neuroblastoma (SHSY5Y) cells. Neurol Res 2011;33:708-16. https://doi.org/10.1179/1743132810Y.0000000028
  17. Chang B, Nishikawa M, Nishiguchi S, Inoue M. L-carnitine inhibitshepatocarcinogenesis via protection of mitochondria. Int J Cancer 2005;113:719-29. https://doi.org/10.1002/ijc.20636
  18. Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L. L-carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept 2010;161:58-66. https://doi.org/10.1016/j.regpep.2009.12.024
  19. Wachter S, Vogt M, Kreis R, Boesch C, Bigler P, Hoppeler H, et al. Long-term administration of L-carnitine to humans: effect on skeletal muscle carnitine content and physical performance. Clin Chim Acta 2002;318:51-61. https://doi.org/10.1016/S0009-8981(01)00804-X
  20. Baghaei A, Solgi R, Jafari A, Abdolghaffari AH, Golaghaei A, Asghari MH, et al. Molecular and biochemical evidence on the protection of cardiomyocytes from phosphine-induced oxidative stress, mitochondrial dysfunction and apoptosis by acetyl-L-carnitine. Environ Toxicol Pharmacol 2016;42:30-7. https://doi.org/10.1016/j.etap.2015.12.019
  21. Dokmeci D, Inan M, Basaran UN, Yalcin O, Aydogdu N, Turan FN, et al. Protective effect of L-carnitine on testicular ischaemia-reperfusion injury in rats: cell biochemistry and function: cellular biochemistry and its modulation by active agents or disease. Cell Biochem Funct 2007;25:611-8. https://doi.org/10.1002/cbf.1355
  22. Singh R, Letai A, Sarosiek K. Regulation of apoptosis in health and disease: the balancing act of BCL-2 family proteins. Nature Reviews Mol Cell Bio 2019;20:175-93. https://doi.org/10.1038/s41580-018-0089-8
  23. Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, et al. Flavonoids in cancer and apoptosis. Cancers (Basel) 2018;11:28. https://doi.org/10.3390/cancers11010028
  24. Esmailpoor A, Ghasemian A, Dehnavi E, Peidayesh H, Teimouri M. Physalis alkekengi hydroalcoholic extract enhances the apoptosis in mouse model of breast cancer cells. Gene Rep 2019;15:100366. https://doi.org/10.1016/j.genrep.2019.100366
  25. Yamaguchi R, Lartigue L, Perkins G. Targeting Mcl-1 and other Bcl-2 family member proteins in cancer therapy. Pharmacol Ther 2019;195:13-20. https://doi.org/10.1016/j.pharmthera.2018.10.009
  26. Warren CF, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis 2019;10:177. https://doi.org/10.1038/s41419-019-1407-6
  27. Knight T, Luedtke D, Edwards H, Taub JW, Ge Y. A delicate balance: the BCL-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics. Biochem Pharmacol 2019;162:250-61. https://doi.org/10.1016/j.bcp.2019.01.015
  28. Silva AG, Lopes CF, Carvalho Junior CG, Thome RG, Dos Santos HB, Reis R, et al. WIN55,212-2 induces caspase-independent apoptosis on human glioblastoma cells by regulating HSP70, p53 and Cathepsin D. Toxicol In Vitro 2019;57:233-43. https://doi.org/10.1016/j.tiv.2019.02.009
  29. Moretti S, Famularo G, Marcellini S, Boschini A, Santini G, Trinchieri V, et al. L-carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine. Antioxid Redox Signal 2002;4:391-403. https://doi.org/10.1089/15230860260196191
  30. Hosseinzadeh Colagar A, Karimi F, Jorsaraei SG. Correlation of sperm parameters with semen lipid peroxidation and total antioxidants levels in astheno- and oligoasheno- teratospermic men. Iran Red Crescent Med J 2013;15:780-5. https://doi.org/10.5812/ircmj.6409
  31. Morovvati H, Khaksar Z, Sheibani MT, Anbara H, Kafiabad MA, Moradi HR. Effect of aspartame on histological and histometrical structure of prostate gland in adult mice. Qom Univ Med Sci J 2019;12:14-27. https://doi.org/10.29252/qums.12.12.14
  32. Costa M, Canale D, Filicori M, D'lddio S, Lenzi A. L-carnitine in idiopathic asthenozoospermia: a multicenter study. Italian Study Group on Carnitine and Male Infertility. Andrologia 1994;26:155-9. https://doi.org/10.1111/j.1439-0272.1994.tb00780.x
  33. Vitali G, Parente R, Melotti C. Carnitine supplementation in human idiopathic asthenospermia: clinical results. Drugs Exp Clin Res 1995;21:157-9.
  34. Hinton BT, Snoswell AM, Setchell BP. The concentration of carnitine in the luminal fluid of the testis and epididymis of the rat and some other mammals. J Reprod Fertil 1979;56:105-11. https://doi.org/10.1530/jrf.0.0560105
  35. Sigman M, Glass S, Campagnone J, Pryor JL. Carnitine for the treatment of idiopathic asthenospermia: a randomized, doubleblind, placebo-controlled trial. Fertil Steril 2006;85:1409-14. https://doi.org/10.1016/j.fertnstert.2005.10.055
  36. Micic S, Lalic N, Djordjevic D, Bojanic N, Bogavac-Stanojevic N, Busetto GM, et al. Double-blind, randomised, placebo-controlled trial on the effect of L-carnitine and L-acetylcarnitine on sperm parameters in men with idiopathic oligoasthenozoospermia. Andrologia 2019;51:e13267. https://doi.org/10.1111/and.13267
  37. Ranger AM, Malynn BA, Korsmeyer SJ. Mouse models of cell death. Nat Genet 2001;28:113-8. https://doi.org/10.1038/88815
  38. Bhatia M. Understanding toxicology: mechanisms and applications. Berlin: Springer; 2017.
  39. Hegazy AA, Elsayed N, Ahmad M, Omar N. Effect of Formaldehyde on Rat Testis Structure. Acad Anat Int 2017;3:15-23.
  40. Yang SB, LI CY, Zhang YB. Effects of formaldehyde and benzene on the apoptosis, expression of Bcl-2 and Bax in testicle of mouse. Pract Prev Med 2008;4.
  41. Kang MH, Reynolds CP. Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy. Clin Cancer Res 2009;15:1126-32. https://doi.org/10.1158/1078-0432.CCR-08-0144
  42. Rucker EB 3rd, Dierisseau P, Wagner KU, Garrett L, Wynshaw-Boris A, Flaws JA, et al. Bcl-x and Bax regulate mouse primordial germ cell survival and apoptosis during embryogenesis. Mol Endocrinol 2000;14:1038-52. https://doi.org/10.1210/mend.14.7.0465
  43. Cankorkmaz L, Koyluoglu G, Ozer H, Yildiz E, Sumer Z, Ozdemir O. The role of apoptosis and protective effect of carnitine in contralateral testicular injury in experimental unilateral testicular torsion. Ulus Travma Acil Cerrahi Derg 2009;15:529-34.
  44. Altun Z, Olgun Y, Ercetin P, Aktas S, Kirkim G, Serbetcioglu B, et al. Protective effect of acetyl-l-carnitine against cisplatin ototoxicity: role of apoptosis-related genes and pro-inflammatory cytokines. Cell Prolif 2014;47:72-80. https://doi.org/10.1111/cpr.12080

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