Redox modulatory effects of testosterone administration in liver tissue of aging rats

Year 2020, Volume: 45 Issue: 4, 1750 - 1757, 27.12.2020

Karolin Yanar

Abstract

Purpose: The aim of this sudy was to evaluate if testosterone administration possesses any ameliorative effects on age-related redox imbalance in liver tissue of male rats.
Materials and Methods: Our study consists of three groups of male rats (n=24). Group 1: Young controls and Group 2: Aged rats that were administrated peanut oil intramuscularly andGroup 3: Aged rats that were administered a single dose of testosterone enanthate (25 mg/kg body weight) in peanut oil intramuscularly as a vehicle. To determine oxidative damage and also antioxidative capacity, we analyzed the levels of protein carbonyl groups, advanced oxidation end products, dityrosine, kynurenine, lipid hydroperoxides, advanced glycation end products, total thiol fractions, and Cu, Zn-superoxide dismutase activities.
Results: The current study results indicate that redox balance is severely impaired in aged liver tissue via higher levels of oxidative protein damage, increased rate of lipid peroxidation, and also reduced antioxidant defense capacity. the present study showed that, testosterone administrationpartially ameliorated impaired redox balance.
Conclusion: Testosterone administration partially improved impaired redox status by alleviating macromolecular oxidative damage and increase antioxidant defense capacity but these ameliorative effects not sufficient as young controls.

Keywords

aging, liver, oxidative stress, redox balance, testosterone

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Bİrimi-5000 TL (ACİP projesi)

Project Number

1719

Thanks

Prof.Dr.Seval Aydın

Yaşlanan karaciğer sıçan dokusunda testosteron uygulamasının redoks modulator etkisi

Abstract

Amaç: Bu çalışmanın amacı, testosteron uygulamasının erkek sıçanların karaciğer dokusunda yaşlanmaya bağlı bozulan redoks homeostasisi üzerine iyileştirici bir etkisinin olup olmadığını değerlendirmektir.
Gereç ve Yöntem: Çalışmamız üç gruptan oluşmaktadır (n=24). Grup 1: Kontrol grubu erkek sıçanlara ve Grup 2: Yaşlı erkek sıçanlara yerfıstığı yağı taşıyıcısı içinde intramusküler olarak verilmiştir. Grup 3’ü oluşturan yaşlı erkek sıçanlara ise tek doz testosteron enanthate (25 mg/kg -) yerfıstığı yağı taşıyıcısı içinde intramuskuler olarak uygulanmıştır. Karaciğer dokusunda makromoleküler hasarı ve antioksidan kapasiteyi belirlemek üzere protein karbonil grupları, ileri oksidasyon protein ürünleri, ditriozin, kinürenin, lipit hidroperoksit, ileri glikasyon son ürünleri, total tiyol fraksiyonları ve Cu, Zn-süperoksit dismutaz aktiviteleri analiz edilmiştir.
Bulgular: Çalışma bulgularımız, yaşlı sıçanların karaciğer dokularında redoks dengesinde ileri düzeyde bir bozulmanın olduğunu artan protein, lipit peroksidasyonu biyobelirteçleri ile ve kısmen azalan antioksidan savunma kapasiteleriyle göstermektedir. Bu çalışmada, testosteron uygulamasının bozulmus redoks dengesinde kısmen iyileştirici yönde etki ettiği saptanmıştır.
Sonuç: Testosteron uygulamasının makromoleküler oksidatif hasarı hafifletmek ve antioksidan kapasiteyi kısmen arttırarak bozulmuş redoks homeostasisini kısmen iyileştirdiği ancak bu etkinin genç kontrollerinki kadar etkili olmadığı sonucuna varılmıştır.

Keywords

yaşlanma, karaciğer, oksidatif stres, redoks dengesi, testosteron

Project Number

1719

References

• 1. Sitar ME, Yanar K, Aydin S, Cakatay U. Current aspects of ageing theories and classification according to mechanisms. Türk Geriatri Dergisi 2013;16(3):339-46.
• 2. Mercado-Sáenz S, Ruiz-Gómez MJ, Morales-Moreno F, Martínez-Morillo M. Cellular aging: theories and technological influence. Braz Arch Biol Technol 2010;53(6):1319-32.
• 3. Sgarbieri VC, Pacheco MTB. Healthy human aging: intrinsic and environmental factors. Braz J Food Technol 2017;20: e2017007.
• 4. Kalaycı I, Özkul M. Geleneksel kalabilsem modern olabilsem: modernleşme sürecinde yaşlilik deneyimleri. Süleyman Demirel Üniversitesi Vizyoner Dergisi 2017;8 (18) 90-110. (Turkish)
• 5. Richardson AG, Schadt EE. The role of macromolecular damage in aging and age-related disease. J Gerontol A Biol Sci Med Sci 2014;69(Suppl_1):S28-S32.
• 6. Stadtman ER. Protein oxidation and aging. Free Radic Res 2006;40(12):1250-8.
• 7. Yanar K, Çakatay U, Aydın S. How various concentrations of nutrients affect basal redox homeostasis of fruit flies according to gender and aging. J Food Biochem 2019;43(12):e13103.
• 8. Erdoğan ME, Aydın S, Yanar K, Mengi M, Kansu AD, Cebe T, et al. The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer’s disease model. Metab Brain Dis 2017;32(4):1017-31.
• 9. Halliwell B, Gutteridge JM (editors). Free radicals in biology and medicine: Oxford University Press, USA; 2015.
• 10. Alexandersen P, Christiansen C. The aging male: testosterone deficiency and testosterone replacement. An up-date. Atherosclerosis 2004;173(2):157-69.
• 11. Zirkin BR, Chen H. Regulation of Leydig cell steroidogenic function during aging. Biol Reprod 2000;63(4):977-81.
• 12. Huang HF, Linsenmeyer TA, Li MT, Giglio W, Anesetti R, von Hagen J, Ottenweller JE, Serenas C, Pogach L Acute effects of spinal cord injury on the pituitary-testicular hormone axis and Sertoli cell functions: a time course study. J Androl 1995; 16(2):148-57.
• 13. Sinclair M, Grossmann M, Gow PJ, Angus PW. Testosterone in men with advanced liver disease: abnormalities and implications. J Gastroenterol Hepatol 2015;30(2):244-51.
• 14. Joksimović J, Selaković D, Jakovljević V, et al. Alterations of the oxidative status in rat hippocampus and prodepressant effect of chronic testosterone enanthate administration. Mol Cell Biochem 2017;433(1-2):41-50.
• 15. Hwang TI, Liao T-L, Lin J-F, Lin Y-C, Lee S-Y, Lai Y-C, et al. Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells. Asian J Androl 2011;13(3):432.
• 16. Skogastierna C, Hotzen M, Rane A, Ekström L. A supraphysiological dose of testosterone induces nitric oxide production and oxidative stress. Eur J Prev Cardio 2014;21(8):1049-54.
• 17. Choobineh H, Gilani MAS, Pasalar P, Jahanzad I, Ghorbani R, Hassanzadeh G. The effects of testosterone on oxidative stress markers in mice with spinal cord injuries. Int J Fertil Steril 2016;10(1):87
• 18. Túnez I, Feijóo M, Collado JA, Medina FJ, Peña J, Muñoz MdC, et al. Effect of testosterone on oxidative stress and cell damage induced by 3-nitropropionic acid in striatum of ovariectomized rats. Life Sci 2007;80(13):1221-7.
• 19. Geer EB, Shen W. Gender differences in insulin resistance,body composition, and energy balance. Gend Med 2009; 6 Suppl (1): 60-75.
• 20. Xia F, Xu X, Zhai H, Meng Y, Zhang H, Du S, Xu H, Wu H, Lu Y. Castration-induced testosterone deficiency increases fasting glucose associated with hepatic and extra-hepatic insulin resistance in adult male rats. Reprod Biol Endocrinol. 2013;11:106
• 21. Buchanan KL, Evans MR, Goldsmith AR, Bryant DM, Rowe LV. Testosterone influences basal metabolic rate in male house sparrows: a new cost of dominance signalling? Proc Biological Sci 2001;268(1474):1337-44.
• 22. Chainy GB, Samantaray S,SamantaL.Testosterone-induced changes in testicular antioxidant system. Andrologia 1997;29(6):343-9.
• 23. Guzmán DC, Mejía GB, Vázquez IE, García EH, del Angel DS, Olguín HJ. Effect of testosterone and steroids homologues on indolamines and lipid peroxidation in rat brain. J Steroid Biocem Mol Biol 2005;94(4):369-73.
• 24. Tam NN, Gao Y, Leung Y-K, Ho S-M. Androgenic regulation of oxidative stress in the rat prostate: involvement of NAD(P)H oxidases and antioxidant defense machinery during prostatic involution and regrowth. Am J Pathol 2003;163(6):2513-22
• 25. Peltola V, Huhtaniemi I, Metsa-Ketela T, Ahotupa M. Induction of lipid peroxidation during steroidogenesis in the rat testis. Endocrinology 1996;137(1):105–12.
• 26. Simon D, Charles MA, Nahoul K, et al. Association between plasma total testosterone and cardiovascular risk factors in healthy adult men: The Telecom Study. J Clin Endocrinol Metab 1997;82:682–5.
• 27. Gårevik N, Skogastierna C, Rane A, Ekströ L. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase. Substance Abuse Treatment, Prevention, and Policy 2012, 7:12.
• 28. Sengupta P. The Laboratory Rat: Relating Its Age With Human's. Int J Prev Med 2013; 4(6): 624–630.
• 29. Yanar K, Atukeren P, Cebe T, Kunbaz A, Ozan T, Kansu AD, et al. Ameliorative effects of testosterone administration on renal redox homeostasis in naturally aged rats. Rejuvenation Res 2015;18(4):299-312.
• 30. Reznick A, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 1994; 233:357-63.
• 31. Hanasand M, Omdal R, Norheim KB, Gøransson LG, Brede C, Jonsson G. Improved detection of advanced oxidation protein products in plasma. Clin Chim Acta 2012;413(9-10):901-6.
• 32. Sadowska-Bartosz I, Galiniak S, Bartosz G, Rachel M. Oxidative modification of proteins in pediatric cystic fibrosis with bacterial infections. Oxid Med Cell Longev 2014;2014:389629.
• 33. Wolff SP. Ferrous ion oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol 1994;233: 182-9.
• 34. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem 1968;25:192-205.
• 35. Sun Y, Oberley LW, Li Y. A simple method for clinicalassay of superoxide dismutase. Clin Chem 1988; 34:497–500.
• 36. Zengin E, Atukeren P, Kokoglu E, Gumustas MK, Zengin U. Alterations in lipid peroxidation and antioxidant status in different types of intracranial tumors within their relative peritumoral tissues. Clin Neurol Neurosurg. 2009;111(4):345-51
• 37. Aydın S, Atukeren P, Çakatay U, Uzun H, Altuğ T. Gender-dependent oxidative variations in liver of aged rats. Biogerontology 2010;11(3) 335-46.