ERKEK SIÇANLARDA AROKLOR 1254‘ÜN NEDEN OLDUĞU REPRODUKTİF HASARA KARŞI TETRANDRİNİN KORUYUCU ETKİLERİNİN ARAŞTIRILMASI

Yıl 2023, Cilt: 6 Sayı: 1, 80 - 87, 28.02.2023

Feride Özdemir , Aslı Çetin , Osman Çiftçi , Muhterem Aydın , Neşe Başak Türkmen

https://doi.org/10.26650/JARHS2023-1181839

Öz

Amaç: Aroklor (AR) 1254; Kanserojenik, endokrin bozucu, nörotoksik, immünsüpresif, teratojenik etkileri olan polilklorlu bifenil bileşiğidir. Stephania tetrandra S. Moore’un kökünden izole edilen bir bisbenzillizokinolin alkaloid olan Tetrandrin (TET) ise immünomodülatör, anti kanser, anti-inflamatuar etkilere sahiptir. Bu çalışma, AR1254’ün neden olduğu testis hasarına (histolojik, spermatolojik ve oksidatif hasar) karşı TET tedavisinin koruyucu, iyileştirici etkilerini göstermek amacıyla planlandı. Materyal ve Metot: Çalışmamızda 28 adet Sprauge-Dawley cinsi sıçanlar kullanıldı ve rastgele seçilerek 4 gruba ayrıldı. (n=7) Gruplar sırasıyla: Kontrol grubu; (1 ml mısır yağı gastrik gavaj ile), AR1254; (2 mg/kg/gün intraperitonal yolla), TET grubu 30 mg/kg/gün gastrik gavaj ile), AR1254+TET grubu; Aroclor1254 ve TET grubuna uygulan dozlar aynı şekilde uygulanarak oluşturuldu. Deney süresi sonunda sıçanlardan alınan testis dokuları histopatolojik ve biyokimyasal yöntemlerle analiz edildi. Bulgular: AR1254 uygulaması sonucunda sıçan testis dokusunda interstisyel alanda; vakuolizasyon, ödem, vasküler konjesyon, spermatogenik hücrelerde; azalma, bölünmenin herhangi bir evresinde duraksama ve lümene dökülme, epididimal sperm konsantrasyonunda, sperm hareketliliğinde azalma ve anormal sperm oranlarında ise artış gözlendi. AR1254 uygulaması oksidatif stres parametrelerinde artışa ve buna karşılık antioksidan seviyelerinde ise azalışa sebep oldu. Uygulanan TET tedavisi, AR1254’ün neden olduğu histolojik, oksidatif ve sperm hasarını önemli ölçüde iyileştirdi. Sonuç: Bu çalışmada, erkek sıçanlarda AR1254 ile oluşturulan testis dokusu hasarına karşı TET’in koruyucu ve iyileştirici etkileri gösterildi.

Anahtar Kelimeler

Aroklor1254, testis, tetrandrin, sıçan, kaspaz-3

Destekleyen Kurum

İnönü Üniversitesi Bilimsel Araştırma Proje Birimi

Proje Numarası

2013/11

Teşekkür

İnönü Üniversitesi Bilimsel Araştırma Proje Birimi 'ne katkılarından dolayı teşekkür ederiz

THE PROTECTIVE EFFECTS OF TETRANDRINE AGAINST TO HISTOLOGICAL, SPERMATOLOGICAL AND OXIDATIVE DAMAGE INDUCED BY AROCLOR 1254 ON THE MALE RATS REPRODUCTIVE SYSTEM

Öz

Objectives: Aroclor (AR) 1254; has many adverse effects on male reproduction such as carcinogenic, teratogenic, immune and endocrine disruption problems. Tetrandrine (TET), a bisbenzillisoquinoline alkaloid isolated from the root of Stephania tetrandra S. Moore, has protective effects such as immunomodulatory, anti-cancer, and anti-inflammatory. The objective of this study was to investigate the possible curative effects of TET therapy against testicular damage (histological, spermatological and oxidative damage) induced by AR1254. Materials and Methods: Twenty-eight male rats were randomly divided into four equal-sized groups: a control group; (1 ml of corn oil by gastric oral gavage), AR1254 group; (2 mg/kg) AR1254 administered intraperitoneally), TET group; (TET by gastric oral gavage 30 mg/kg) and AR 1254 + TET group;(Aroclor 1254 and TET administered together at the same doses as the previous groups. Results: The AR1254 treatment caused morphological and spermatological damage on testis tissue; oedema vacuolization and congestion, in interstitial area, reduction in spermatogenic cells, arrested spermatocytes at different stages of spermatogenesis, shedding of spermatogenic serial cells into tubular lumens, a decline in epididymal sperm concentrations, sperm motility and a rise in abnormal sperm ratios. The AR1254 administration induced an increase in the oxidative parameters and a decrease in enzymatic and nonenzymatic antioxidant levels. The TET treatment significantly ameliorated histological, oxidative, and sperm damage caused by AR1254. Conclusion: This study demonstrated the protective effects of TET against AR1254-induced male rat reproductive damage.

Anahtar Kelimeler

Aroclor1254, testis, tetrandrine, rat, caspase-3

Proje Numarası

2013/11

Kaynakça

• 1. Lilienthal H, Fastabend A, Hany J, Kaya H, Roth-Härer A, Dunemann L, et al. Reduced levels of 1, 25-dihydroxyvitamin D3 in rat dams and offspring after exposure to a reconstituted PCB mixture. Toxicol Sci 2000;57(2):292-301. google scholar
• 2. Carpenter DO. Polychlorinated biphenyls and human health. Int J Occup Med Environ Health 1998;11(4):291-303. google scholar
• 3. Kamrin M, Ringer R. PCB residues in mammals: A review. Toxicol Enviro Chem 1994;41(1-2):63-84. google scholar
• 4. Carpenter DO. Environmental contaminants and human health: the health effects of persistent toxic substances. Fırat Med J 2005;10(1):1-4. google scholar
• 5. Kimbrough RD, Krouskas CA. Human Exposure to Polychlorinated Biphenyls and Health Effects. Toxicol Rev 2003;22(4):217-33. google scholar
• 6. Mazen NF, Zidan RA. Histological study on the effect of aroclor 1254 on the epididymis of adult rats and the role of L-NAME administration. Ultrastruct Pathol 2017;41(2):154-67. google scholar
• 7. Krishnamoorthy G, Murugesan P, Muthuvel R, Gunadharini D, Vijayababu M, Arunkumar A, et al. Effect of Aroclor 1254 on Sertoli cellular antioxidant system, androgen binding protein and lactate in adult rat in vitro. Toxicology 2005;212(2-3):195-205. google scholar
• 8. Murugesan P, Kanagaraj P, Yuvaraj S, Balasubramanian K, Aruldhas MM, Arunakaran J. The inhibitory effects of polychlorinated biphenyl Aroclor 1254 on Leydig cell LH receptors, steroidogenic enzymes and antioxidant enzymes in adult rats. Reprod Toxicol 2005;20(1):117-26. google scholar
• 9. Aly HA, Domènech O, Abdel-Naim AB. Aroclor 1254 impairs spermatogenesis and induces oxidative stress in rat testicularmitochondria. Food Chem Toxicol 2009;47(8):1733-8. google scholar
• 10. Ahmad SU, Tariq S, Jalali S, Ahmad MM. Environmental pollutant Aroclor 1242 (PCB) disrupts reproduction in adult male rhesus monkeys (Macaca mulatta). Environ Res 2003;93(3):272-8. google scholar
• 11. Krishnamoorthy G, Venkataraman P, Arunkumar A, Vignesh R, Aruldhas M, Arunakaran J. Ameliorative effect of vitamins (a-tocopherol and ascorbic acid) on PCB (Aroclor 1254) induced oxidative stress in rat epididymal sperm. Reprod Toxicol 2007;23(2):239-45. google scholar
• 12. Alston DA, Tandler B, Gentles B, Smith EE. Testicular histopathology in deer mice (Peromyscus maniculatus) following exposure to polychlorinated biphenyl. Chemosphere 2003;52(1):283-5. google scholar
• 13. Atejjahin A, Türk G, Yilmaz S, Sönmez M, Sakin F, Qeribasi AO. Modulatory effects of lycopene and ellagic acid on reproductive dysfunction induced by polychlorinated biphenyl (Aroclor 1254) in male rats. Basic Clin Pharmacol Toxicol 2010;106(6):479-89. google scholar
• 14. Ruan L, Huang HS, Jin WX, Chen H-M, Li XJ, Gong Q-J. Tetrandrine attenuated cerebral ischemia/reperfusion injury and induced differential proteomic changes in a MCAO mice model using 2-D DIGE. Neurochem Res 2013;38(9):1871-9. google scholar
• 15. Zhang J, Yu B, Zhang XQ, Sheng ZF, Li SJ, Wang ZJ, et al. Tetrandrine, an antihypertensive alkaloid, improves the sleep state of spontaneously hypertensive rats (SHRs). J Ethnopharmacol 2014;151(1):729-32. google scholar
• 16. Yin M-F, Lian LH, Piao D-M, Nan J-X. Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model. World J Gastroenterol 2007;13(8):1214-20. google scholar
• 17. Chen Y, Tsai YH, Tseng SH. The potential of tetrandrine as a protective agent for ischemic stroke. Molecules 2011;16(9):8020-32. google scholar
• 18. Murugesan P, Muthusamy T, Balasubramanian K, Arunakaran J. Studies on the protective role of vitamin C and E against polychlorinated biphenyl (Aroclor 1254)—induced oxidative damage in Leydig cells. Free Radic Res 2005;39(11):1259-72. google scholar
• 19. Zhong Z, Qian Z, Zhang X, Chen F, Ni S, Kang Z, et al. Tetrandrine prevents bone loss in ovariectomized mice by inhibiting RANKL-induced osteoclastogenesis. Front Pharmacol 2020;10:1530. google scholar
• 20. Lv Yl, Wu Zz, Chen Lx, Wu Bx, Chen Ll, Qin Gc, et al. Neuroprotective effects of tetrandrine against vascular dementia. Neural Regen Rese 2016;11(3):454-59. google scholar
• 21. Türk G, Sönmez M, Aydin M, Yüce A, Gür S, Yüksel M, et al. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clin Nutr 2008;27(2):289-96. google scholar
• 22. Ciftci O, Ozdemir I, Aydin M, Beytur A. Beneficial effects of chrysin on the reproductive system of adult male rats. Andrologia 2012;44(3):181-6. google scholar
• 23. Yagi K. Simple assay for the level of total lipid peroxides in serum or plasma. Free radical and antioxidant protocols: Methods Mol Biol. Springer; 1998.DOi: p. 101-6. 10.1385/0-89603-472-0:10 google scholar
• 24. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959;82(1):70-7. google scholar
• 25. Aebi H. Catalase in vitro. Methods in enzymology 1984;105:121-6. google scholar
• 26. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem 1988;34(3):497-500. google scholar
• 27. Beutler E. Red cell metabolism: a manual of biochemical methods. 1984. google scholar
• 28. Çakıroğulları GÇ, Seçer S. Poliklorlu Bifeniller ve Sucul Yaşam. Ankara Üniversitesi Çevrebilimleri Dergisi 2011;3(1):73-88. google scholar
• 29. Ahlborg UG, Hanberg A, Kenne K. Risk assessment of polychlorinated biphenyls (PCBs): Document for Risk Assessment, Institute of Environmental Medicine, Stockholm, Sweden; 1992. ISBN: 9291200751, ISSN: 0903-7004. google scholar
• 30. Hsu PC, Li MH, Guo YL. Postnatal exposure of 2, 2‘, 3, 3‘, 4, 6‘-hexachlorobiphenyl and 2, 2‘, 3, 4‘, 5‘, 6-hexachlorobiphenyl on sperm function and hormone levels in adult rats. Toxicology 2003;187(2-3):117-26. google scholar
• 31. Hsu PC, Pan MH, Li LA, Chen CJ, Tsai SS, Guo YL. Exposure in utero to 2, 2‘, 3, 3‘, 4, 6‘-hexachlorobiphenyl (PCB 132) impairs sperm function and alters testicular apoptosis-related gene expression in rat offspring. Toxicol Appl Pharmacol 2007;221(1):68-75. google scholar
• 32. Aydin S, Erkekoglu P, Başaran N, Kocer-Gumusel B. Impact of selenium status on Aroclor 1254-induced DNA damage in sperm and different tissues of rats. Toxicol Mech Methods 2018;28(4):252-61. google scholar
• 33. Lopes Moreno JM. Effect of Pcbs (Aroclor 1254) on spermatogenesis In Testis of Mouse 2009. pp.1-61. Available from: http:// www.portaldoconhecimento.gov.cv/bitstream/10961/67/1/ EFFECT%20of%20PCBs%20%28AROCLOR%201254%29%20on%20 Spermatogenesis%20in%20testis%20of%20mouse.pdf google scholar
• 34. Jia X, Xu Y, Wu W, Fan Y, Wang G, Zhang T, et al. Aroclor1254 disrupts the blood-testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway. Cell Death Dis 2017;8(5):e2823-e. doi: 10.1038/cddis.2017.224 google scholar
• 35. Sangalang G, Freeman H, Crowell R. Testicular abnormalities in cod (Gadus morhua) fed Aroclor 1254. Arch Environ Contam Toxicol 1981;10(5):617-26. google scholar
• 36. Oskam IC, Lyche JL, Krogen^s A, Thomassen R, Skaare JU, Wiger R, et al. Effects of long-term maternal exposure to low doses of PCB126 and PCB153 on the reproductive system and related hormones of young male goats. Reproduction 2005;130(5):731-42. google scholar
• 37. Luan F, He X, Zeng N. Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems. J Pharm Pharmacol 2020;72(11):1491-512. google scholar
• 38. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35(4):495-516. google scholar
• 39. Yang GS, Wang W, Wang YM, Chen ZD, Wang S, Fang JJ. Effect of cocaine on germ cell apoptosis in rats at different ages. Asian J Androl 2006;8(5):569-75. google scholar
• 40. Mathur PP, Huang L, Kashou A, Vaithinathan S, Agarwal A. Environmental toxicants and testicular apoptosis. Open Reprod Sci J 2011;3(1):114-24. google scholar
• 41. Liu C, Gong K, Mao X, Li W. Tetrandrine induces apoptosis by activating reactive oxygen species and repressing Akt activity in human hepatocellular carcinoma. Int J Cancer 2011;129(6):1519-31. google scholar
• 42. Gong K, Chen C, Zhan Y, Chen Y, Huang Z, Li W. Autophagy-related gene 7 (ATG7) and reactive oxygen species/extracellular signal-regulated kinase regulate tetrandrine-induced autophagy in human hepatocellular carcinoma. J Biol Chem 2012;287(42):35576-88. google scholar
• 43. Aitken RJ, Roman SD. Antioxidant systems and oxidative stress in the testes. Adv Exp Med Biol 2008;636:154-71. google scholar
• 44. Kaya K, Ciftci O, Aydın M, Cetin A, Basak N. Favourable effect of ß-glucan treatment against cisplatin-induced reproductive system damage in male rats. Andrologia 2019;51(9):e13342. doi: 10.1111/ and.13342 google scholar
• 45. Banudevi S, Sharmila M, Murugesan P, Srinivasan N, Balasubramanian K, Aruldhas M, et al. Effects of Vitamin C and E on PCB (Aroclor 1254) induced oxidative stress, androgen binding protein and lactate in rat Sertoli cells. Reprod Toxicol 2004;19(2):201-8. google scholar
• 46. Zhang YMC. Protective effect of quercetin on Aroclor 1254-induced oxidative damage in cultured chicken spermatogonial cells. Toxicol Sci 2005;88(2):545-50. google scholar
• 47. Venkataraman P, Sridhar M, Dhanammal S, Vijayababu M, Srinivasan N, Arunakaran J. Antioxidant role of zinc in PCB (Aroclor 1254) exposed ventral prostate of albino rats. J Nutr Biochem. 2004;15(10):608-13. google scholar
• 48. Koh SB, Ban JY, Lee BY, Seong YH. Protective effects of fangchinoline and tetrandrine on hydrogen peroxide-induced oxidative neuronal cell damage in cultured rat cerebellar granule cells. Planta Medica 2003;69(6):506-12. google scholar
• 49. Li YY, Li XL, Yang CX, Zhong H, Yao H, Zhu L. Effects of tetrandrine and QYT on ICAM-1 and SOD gene expression in pancreas and liver of rats with acute pancreatitis. World J Gastroenterol 2003;9(1):155-59. google scholar
• 50. Hui SC, Chan TY, Chen YY. Tetrandrine inhibits lipid peroxidation but lacks reactivity towards superoxide anion and hydrogen peroxide. Pharmacol Toxicol 1996;78(3):200-1. google scholar