Beneficial Effects of Exercise and Estrogen in Maintaining Oxidant/Antioxidant Balance in the Liver and Kidney Tissues of Rats with Ovariectomy

Abstract

Objective: The aim of this study was to investigate the effects of estrogen or exercise or estrogen-exercise combination on oxidant damage and histopathological and functional changes observed in kidney and liver of rats with surgical menopause.

Materials and Methods: Bilateral ovariectomy was performed on female Sprague Dawley rats (n=32) under anesthesia and all rats were randomly divided into two groups. Half of the rats were given normal drinking water, and the other half had estrogen (1mg/kg/day) added to their drinking water. Two weeks later, the groups were divided into sedentary and exercise (5 days/week, 30 minutes, 8 weeks) groups. At the end of the experimental protocol, serum, liver and kidney samples were taken for biochemical and histopathological examinations. Femur was also examined histopathologically.

Results: In ovariectomized rats, estrogen showed a protective effect by suppressing neutrophil infiltration and production of reactive oxygen species in kidney tissue, causing a slight increase in bone mass, with a decrease in hepatic antioxidant glutathione level. On the other hand, estrogen application prevented the oxidant stress in the liver due to the exercise performed in menopause. While kidney functions were not significantly affected by exercise or the addition of estrogen therapy to exercise, more favorable changes were observed in bone structure compared to estrogen alone.

Conclusion: In addition to the positive effects of estrogen replacement on bone tissue, estrogen reduces oxidant stress in the liver and kidney and shows a protective effect by suppressing the oxidant stress that develops especially in the liver due to exercise.

Keywords

• Exercise
• menopause
• oxidant damage
• estrogen.

Cerrahi Menopoz Oluşturulmuş Sıçanların Karaciğer ve Böbrek Dokularında Oksidan/Antioksidan Dengenin Korunmasında Egzersizin ve Östrojenin Yararlı Etkileri

Öz

Amaç: Bu çalışmanın amacı cerrahi olarak menopoz oluşturulan sıçanların böbrek ve karaciğerlerinde gözlenen histopatolojik ve fonksiyonel değişiklikleri ve östrojen veya egzersizin ya da östrojen-egzersiz kombinasyonunun oksidan hasar üzerine etkilerini araştırmaktır.

Materyal ve Metot: Anestezi altında Sprague Dawley dişi sıçanlara (n=32) bilateral overiektomi uygulandı ve tüm sıçanlar rastgele olarak iki gruba ayrıldı. Sıçanların yarısına normal içme suyu, diğer yarısının içme sularına östrojen (1mg/kg/gün) eklendi. İki hafta sonra gruplar kendi içlerinde sedanter ve egzersiz (5 gün/hafta, 30 dakika, 8 hafta) gruplarına ayrıldı. Deney protokolünün sonunda serum, karaciğer ve böbrek örnekleri biyokimyasal ve histopatolojik incelemeler için alındı. Femurda da histopatolojik değerlendirme yapıldı.

Bulgular: Cerrahi olarak menopoz oluşturulan sıçanlarda östrojenin böbrek dokusunda nötrofil infiltrasyonunu ve reaktif oksijen türlerinin üretimini baskılayarak koruyucu etki gösterdiği, kemik kütlesinde hafif düzeyde artışa neden olduğu, ancak karaciğerin antioksidan glutatyon düzeyinde azalmaya yol açtığı belirlenmiştir. Buna karşın, östrojen uygulaması menopozda yapılan egzersiz nedeniyle karaciğerde oluşan oksidan stresi engellemiştir. Egzersizle veya egzersize östrojen tedavisinin eklenmesiyle böbrek fonksiyonları önemli ölçüde etkilenmezken, kemik yapısında tek başına östrojene kıyasla daha olumlu değişiklikler gözlenmiştir.

Sonuç: Östrojen replasmanı kemik dokusundaki olumlu etkilerinin yanı sıra karaciğer ve böbrekte oksidan stresi azaltmakta ve özellikle karaciğerde egzersize bağlı gelişen oksidan stresi baskılayarak koruyucu etki göstermektedir.

Anahtar Kelimeler

• Egzersiz
• menapoz
• oksidan hasar
• östrojen

Kaynakça

1. Kuller LH, Meilahn EN, Cauley JA, Gutai JP, Matthews KA. Epidemiologic studies of menopause: changes in risk factors and disease. Exp Gerontol. 1994;29(3-4):495-509.
2. Santo Signorelli S, Neri S, Sciacchitano S, et al. Behaviour of some indicators of oxidative stress in postmenopausal and fertile women. Maturitas. 2006;53(1):77-82.
3. Sánchez-Rodríguez MA, Zacarías-Flores M, Arronte-Rosales A, Correa-Muñoz E, Mendoza-Núñez VM. Menopause as risk factor for oxidative stress. Menopause. 2012;19(3):361-367.
4. Şen E, Saruhan A. Menopoz ve hormon replasman tedavisi ile ilgili kanıta dayalı çalışmalar. Sosyal Politika Çalışmaları Dergisi. 2010;20(20):45-52.
5. Miller VT, LaRosa J, Barnabei V, et al. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women: the postmenopausal estrogen/progestin interventions (PEPI) trial. Jama. 1995;273(3):199-208.
6. Pradhan AD, Manson JE, Rossouw JE, et al. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study. Jama. 2002;288(8):980-987.
7. Siddiqui N, Rahman S, Mia A, Shamsuzzaman A. Evaluation of hormone replacement therapy. Mymensingh Med J. 2005;14(2):212-218.
8. Orri JC, Hughes EM, Mistry DG, Scala AH. Is Vigorous Exercise Training Superior to Moderate for CVD Risk after Menopause? Sports Med Int Open. 2017;1(5):E166-E171.

9. Radák Z, Young Chung H, Naito H, et al. Age‐associated increases in oxidative stress and nuclear transcription factor κB activation are attenuated in rat liver by regular exercise. FASEB J. 2004;18(6):749-750.
10. Souza CS, de Sousa Oliveira BS, Viana GN, et al. Preventive effect of exercise training on diabetic kidney disease in ovariectomized rats with type 1 diabetes. Exp Biol Med. 2019;244(9):758-769.
11. Nakajima D, Kim C-S, Oh T-W, et al. Suppressive effects of genistein dosage and resistance exercise on bone loss in ovariectomized rats. J Physiol Anthropol Appl Human Sci. 2001;20(5):285-291.
12. Babayev H, Arabaci-Tamer S, Yildirim A, et al. Sleeve gastrectomy–induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: role of the estrogen receptors. Surg Obes Relat Dis. 2021;17(1):193-207.
13. Arabacı Tamer S, Koyuncuoğlu T, Karagöz Köroğlu A, Akakın D, Yüksel M, Yeğen BÇ. Nesfatin-1 ameliorates oxidative brain damage and memory impairment in rats induced with a single acute epileptic seizure. Life Sci. 2022;294:120376.
14. Fischer V, Haffner-Luntzer M. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Semin Cell Dev Biol. 2022;123:14-21.
15. Gürler EB, Çilingir‐Kaya ÖT, Peker Eyüboglu I, et al. Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats. Cell Biochem Funct. 2019;37(2):102-112.
16. Zhao R, Zhou Y, Li J, Lin J, Cui W, Peng Y, Bu W. Irisin Regulating Skeletal Response to Endurance Exercise in Ovariectomized Mice by Promoting Akt/β-Catenin Pathway. Front Physiol. 2021;12:639066.
17. Going S, Lohman T, Houtkooper L, et al. Effects of exercise on bone mineral density in calcium-replete postmenopausal women with and without hormone replacement therapy. Osteoporos Int. 2003;14(8):637-643.
18. Chong CLG, Hussan F, Othman F. Hepatoprotective Effects of Morinda citrifolia Leaf Extract on Ovariectomized Rats Fed with Thermoxidized Palm Oil Diet: Evidence at Histological and Ultrastructural Level. Oxid Med Cell Longev. 2019;2019:9714302.
19. Koyuncuoğlu T, Arabacı Tamer S, Erzik C, et al. Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure. Exp Physiol. 2019;104(12):1911-1928.
20. Tamer SA, Yıldırım A, Arabacı Ş, et al. Treatment with estrogen receptor agonist ERβ improves torsion-induced oxidative testis injury in rats. Life Sci. 2019;222:203-211.
21. Ribon-Demars A, Pialoux V, Boreau A, Marcouiller F, Larivière R, Bairam A, Joseph V. Protective roles of estradiol against vascular oxidative stress in ovariectomized female rats exposed to normoxia or intermittent hypoxia. Acta Physiol (Oxf). 2019;225(2):e13159.
22. El-Gendy AA, Elsaed WM, Abdallah HI. Potential role of estradiol in ovariectomy-induced derangement of renal endocrine functions. Ren fail. 2019;41(1):507-520.
23. Nahavandi S, Ahmadi S, Sobhani SA, Abbasi T, Dehghani A. A high dose of estrogen can improve renal ischemia-reperfusion-induced pulmonary injury in ovariectomized female rats. Can J Physiol Pharmacol. 2021;99(12):1241-1252.
24. Aapkes SE, Bernts LHP, Barten TRM, van den Berg M, Gansevoort RT, Drenth JPH. Estrogens in polycystic liver disease: A target for future therapies? Liver Int. 2021 Sep;41(9):2009-2019.
25. El Hajj A, Wardy N, Haidar S, Bourgi D, Haddad ME, Chammas DE, El Osta N, Rabbaa Khabbaz L, Papazian T. Menopausal symptoms, physical activity level and quality of life of women living in the Mediterranean region. PLoS One. 2020;15(3):e0230515.
26. Sun Y, Liang C, Zheng L, Liu L, Li Z, Yang G, Li Y. Anti-fatigue effect of hypericin in a chronic forced exercise mouse model. J Ethnopharmacol. 2022;284:114767.