TY - JOUR T1 - INVESTIGATION OF THE EFFECT OF Pistacia Terebinthus L. EXTRACT ON ISCHEMIA/REPERFUSION INJURY INDUCED BY EXPERIMENTAL TORSION/DETORSION IN THE TESTIS TT - Pistacia Terebinthus L. Ekstresinin Testiste Deneysel Torsiyon/Detorsiyonun Neden Olduğu İskemi/Reperfüzyon Hasarı Üzerindeki Etkisinin Araştırılması AU - Erdemci, Fikri AU - Deveci, Engin AU - Aşır, Fırat PY - 2026 DA - May Y2 - 2026 DO - 10.30934/kusbed.1894271 JF - Kocaeli Üniversitesi Sağlık Bilimleri Dergisi JO - KOU Sag Bil Derg PB - Kocaeli University WT - DergiPark SN - 2149-8571 SP - 119 EP - 126 VL - 12 IS - 2 LA - en AB - Objective: Testicular torsion (TT), one of the urological emergencies requiring urgent intervention, can lead to testicular atrophy, impaired testicular function, and infertility in some patients if not treated promptly. Oxidative stress resulting from the excessive accumulation and increase of reactive oxygen species (ROS) due to ischemia-reperfusion (I/R) injury is the primary cause of pathological changes occurring during I/R. Pistacia terebinthus is extremely rich in phenolic compounds, tocopherols, and flavonoids. Due to these properties, it exhibits antioxidant activity along with anti-inflammatory, antimicrobial, and cytotoxic properties. This study aimed to investigate the potential protective and therapeutic effects of PT extract on testicular tissue in an experimentally generated testicular T/D model. For this purpose, histochemical and immunohistochemical techniques were used.Methods: A total of 48 male Sprague-Dawley rats were randomly divided into six experimental groups: Sham, Pistacia terebinthus (PT), Torsion/Detorsion (T/D), PT+T/D, T/D+PT, and PT+T/D+PT. The torsion-detorsion procedure involved rotating the animals' right and left testes 720° for three hours, followed by detorsion procedures. The PT extract was administered orally to the animals at a dose of 2 ml/kg according to the protocol. The testes were collected after completion of the experiment to perform histopathological and immunohistochemical evaluations.Results: Similarly in the Sham and PT groups, seminiferous tubules were normal, and 5-6 rows of germinal epithelium were observed in the basal lamina. The appearance of capillaries and Leydig cells in the interstitial area was normal. In animals in the T/D group, damage to the seminiferous tubules, deterioration of spermatogenic cells, bleeding in the interstitial area, edema, and blockage of the vessels were observed. Partial improvement, dilatation, and vascular occlusion were observed in the seminiferous tubules of animals in the P+T/D group. In the T/D+PT and PT+T/D+PT groups, features similar to the sham group were observed in the basal lamina, and vascular occlusion was observed. A total of 80 seminiferous tubules, randomly selected from sections taken from each group, were evaluated according to the Johnsen biopsy grading system. The evaluation revealed similar results between the sham and PT groups, while significant differences were observed among the other groups.Conclusion: PT extract has been shown to have a regenerative effect on damage caused by torsion-detorsion in the testis. Furthermore, PT extract was found to support cell survival by suppressing Apaf-1 expression, while also ensuring the continuation of spermatogenesis by increasing Sox-9 expression in the treatment groups. These results highlight the importance of further research into the protective and therapeutic potential of PT extract in cases of T/D damage. KW - Ischemia-reperfusion KW - Antioxidant KW - Pistacia terebinthus KW - Testis KW - Torsion-detorsion N2 - Amaç: Acil müdahale gerektiren ürolojik acil durumlardan biri olan testis torsiyonu (TT), zamanında tedavi edilmezse bazı hastalarda testis atrofisine, testis fonksiyon bozukluğuna ve kısırlığa yol açabilir. İskemi-reperfüzyon (I/R) hasarı nedeniyle reaktif oksijen türlerinin (ROS) aşırı birikimi ve artışından kaynaklanan oksidatif stres, I/R sırasında meydana gelen patolojik değişikliklerin birincil nedenidir. Pistacia terebinthus, fenolik bileşikler, tokoferoller ve flavonoidler açısından son derece zengindir. Bu özellikleri nedeniyle, antiinflamatuar, antimikrobiyal ve sitotoksik özelliklerin yanı sıra antioksidan aktivite de sergiler. Bu çalışma, deneysel olarak oluşturulan testis T/D modelinde PT ekstresinin testis dokusu üzerindeki potansiyel koruyucu ve terapötik etkilerini araştırmayı amaçlamıştır. Bu amaçla, histokimyasal ve immünohistokimyasal teknikler kullanılmıştır.Yöntem: Toplam 48 erkek Sprague-Dawley sıçanı rastgele altı deney grubuna ayrıldı: Sham, Pistacia terebinthus (PT), Torsiyon/Detorsiyon (T/D), PT+T/D, T/D+PT ve PT+T/D+PT. Torsiyon-detorsiyon prosedürü, hayvanların sağ ve sol testislerinin üç saat boyunca 720° döndürülmesini ve ardından detorsiyon prosedürlerinin uygulanmasını içeriyordu. PT ekstresi, protokole göre hayvanlara 2 ml/kg dozunda oral olarak uygulandı. Deneyin tamamlanmasının ardından testisler, histopatolojik ve immünohistokimyasal değerlendirmeler yapmak üzere alındı.Bulgular: Sham ve PT gruplarında benzer şekilde, seminifer tübüller normaldi ve bazal laminada 5-6 sıra germinal epitel gözlendi. İnterstisyel alanda kılcal damarların ve Leydig hücrelerinin görünümü normaldi. T/D grubundaki hayvanlarda seminifer tübüllerde hasar, spermatogenik hücrelerde bozulma, interstisyel alanda kanama, ödem ve damar tıkanıklığı gözlendi. P+T/D grubundaki hayvanların seminifer tübüllerinde kısmi iyileşme, dilatasyon ve vasküler oklüzyon gözlendi. T/D+PT ve PT+T/D+PT gruplarında, bazal laminada sham grubuna benzer özellikler gözlendi ve vasküler oklüzyon gözlendi.Sonuç: PT ekstraktının testiste torsiyon-detorsiyonun neden olduğu hasar üzerinde rejeneratif bir etkiye sahip olduğu gösterilmiştir. Ayrıca, PT ekstraktının Apaf-1 ekspresyonunu baskılayarak hücre sağkalımını desteklediği ve aynı zamanda tedavi gruplarında Sox-9 ekspresyonunu artırarak spermatogenezin devamını sağladığı bulunmuştur. Bu sonuçlar, T/D hasarı vakalarında PT ekstraktının koruyucu ve terapötik potansiyeli hakkında daha fazla araştırma yapılmasının önemini vurgulamaktadır. CR - Huang WY, Chen YF, Chang HC, Yang TK, Hsieh JT, Huang KH. The incidence rate and characteristics in patients with testicular torsion: a nationwide, population‐based study. Acta Paediatrica. 2013;102(8):e363-e7. doi:10.1111/apa.12275 CR - Prater JM, Overdorf BS. Testicular torsion: a surgical emergency. Am Fam Physician. 1991;44(3):834-840. CR - Heyns C, Visser A. Testicular torsion. Andrology for the Clinician: Springer; 2006:134-161. CR - Wei S-M, Yan Z-Z, Zhou J. Protective effect of rutin on testicular ischemia-reperfusion injury. Journal of pediatric surgery.2011;46(7):1419-1424. doi:10.1016/j.jpedsurg.2010.09.044 CR - Turner T, Tung KS, Tomomasa H, Wilson LW. Acute testicular ischemia results in germ cell-specific apoptosis in the rat. Biol Reprod. 1997;57(6):1267-1274. doi:10.1016/S0022-5347(01)62473-X CR - Lysiak JJ, Nguyen QAT, Kirby JL, Turner TT. Ischemia-reperfusion of the murine testis stimulates the expression of proinflammatory cytokines and activation of c-jun N- terminal kinase in a pathway to E-selectin expression. Biol Reprod. 2003;69(1):202-210. doi:10.1095/biolreprod.102.013318 CR - Elshaari F, Elfagih R, Sheriff D, Barassi I. Oxidative and antioxidative defense system in testicular torsion/detorsion. Indian J Urol. 2011;27(4):479-484. doi:10.4103/0970-1591.91436 CR - Turner TT, Lysiak JJ. Oxidative stress: a common factor in testicular dysfunction. J Androl. 2008;29(5):488-498. doi:10.2164/jandrol.108.005132 CR - Shinde A, Ganu J, Naik P. Effect of free radicals & antioxidants on oxidative stress: a review. J Dent Allied Sci. 2012;1(2):63. doi:10.4103/2277-4696.159144 CR - Khezri MR, Ghasemnejad-Berenji H, Ghasemnejad-Berenji M. Protective effects of empagliflozin on testicular injury induced by torsion/detorsion in adult male rats. J Pediatr Urol. 2023;19(5):545. doi:10.1016/j.jpurol.2023.06.016 CR - Tastekin D, Tambas M, Kilic K, Erturk K, Arslan D. The efficacy of Pistacia Terebinthus soap in the treatment of cetuximab-induced skin toxicity. Invest New Drugs. 2014; 32(1):1295-1300. doi:10.1007/s10637-014-0128-z CR - Özyurt M, Kopar H, Özyurt S, Demirhan İ, Kurutas EB. Investigation of Antioxidant Activity In Menengiç, Işgın and Çiriş Otu. KSU J Agric Nat. 2021;24(4):733-737. doi:10.18016/ksutarimdoga.vi.819974 CR - Hacıbekiroğlu II, Yılmaz PK, Ha¸ imi N, Kılınç E, Tolan V, Kolak U. In vitro biological activities and fatty acid profiles of Pistacia terebinthus fruits and Pistacia khinjuk seeds. Nat Prod Res. 2015;29(5):444-446. doi:10.1080/14786419.2014.947492 CR - Uyar A, Abdulrahman NT. A histopathological, immunohistochemical and biochemical investigation of the antidiabetic effects of the Pistacia terebinthus in diabetic rats. Biotech Histochem. 2020;95(2):92-104. doi:10.1080/10520295.2019.1612092 CR - Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1(1):2-25. doi:10.1159/000178170 CR - Ellati RT, Kavoussi PK, Turner TT, Lysiak JJ. Twist and shout: a clinical and experimental review of testicular torsion. Korean J Urol. 2009;50(12):1159-1167. doi:10.4111/kju.2009.50.12.1159 CR - Visser AJ, Heyns CF. Testicular function after torsion of the spermatic cord. BJU Int. 2003;92(3). doi:10.1046/j.1464-410X.2003.04307.x CR - Akgür FM, Kilinç K, Aktuǧ T, Olguner M. The effect of allopurinol pretreatment before detorting testicular torsion. J Urol. 1994;151(6):1715-1717. doi:10.1016/S0022-5347(17)35351-X CR - Southorn PA., Powis G. Free radicals in medicine. I. Chemical nature and biologic reactions. In Mayo Clinic Proceedings. 1988; Vol. 63, No. 4, pp. 381-389). Elsevier. doi:10.1016/S0025-6196(12)64861-7 CR - Saçık U, Çavdar Z, Ural C, Ersoy N, Özoğul C, Erbil G. Effect of ferulic acid on testicular damage causedby torsion-detorsion in rats. Biotech Histochem. 2023;98(2):77-85. doi:10.1080/10520295.2022.2110615 CR - Yesil S, Ozdemir C, Arslan M, Gundogdu AC, Kavutcu M, Atan A. Protective effect of cerium oxide on testicular function and oxidative stress after torsion/detorsion in adult male rats. Exp Ther Med. 2022;25(1):1. doi:10.3892/etm.2022.11700 CR - Oz S, Dönmez D, Üstüner M, Hız İ, Özden H, Kabay Ş. Protective Effects of Capsaicin on Experimental Testicular Torsion and Detorsion Injury. J Urol Surg. 2023;10(1). doi:10.4274/jus.galenos.2022.2022.0011 CR - Ramesh M, Mojaverrostami S, Khadivi F, Rastegar T, Abbasi Y, Bashiri Z. Protective effects of human amniotic membrane derived mesenchymal stem cells (hAMSCs) secreted factors on mouse spermatogenesis and sperm chromatin condensation following unilateral testicular torsion. Ann Anat. 2023;249:152084. doi:10.1016/j.aanat.2023.152084 CR - Sekmenli T, Gunduz M, Öztürk B, et al. The effects of melatonin and colchicine on ischemia–reperfusion injury in experimental rat testicular torsion model. J Pediatr Surg. 2017;52(4):582-586. doi:10.1016/j.jpedsurg.2016.11.035 CR - Samy A, El-Adl M, Rezk S. et al. The potential protective and therapeutic effects of platelet-rich plasma on ischemia/reperfusion injury following experimental torsion/detorsion of testis in the Albino rat model. Life Sci. 2020;256:117982. doi:10.1016/j.lfs.2020.117982 CR - Elshaari FA, Elfagih RI, Sheriff DS, Barassi IF. Testicular torsion-detorsion-histological and biochemical changes in rat testis. J Cytol Histol. 2012;3(01):1000316. doi:10.4172/2157-7099.1000136 CR - Foddai M, Kasabri V, Afifi FU, Azara E. Petretto GL, Pintore G. In vitro inhibitory effects of Sardinian Pistacia lentiscus L. and Pistacia terebinthus L. on metabolic enzymes: Pancreatic lipase, α‐amylase, and α‐glucosidase. Starch‐Stärke. 2015;67(1-2):204-212. doi:10.1002/star.201400068 CR - Gogus F, Ozel MZ, Kocak D, Hamilton JF, Lewis AC. Analysis of roasted and unroasted Pistacia terebinthus volatiles using direct thermal desorption-GCxGC–TOF/MS. Food Chem. 2011;129(3):1258-1264. doi:10.1016/j.foodchem.2011.05.003 CR - Gocer H. Antioxidant properties of terebinth (pistacia terebin thus l.) seeds. Int J Academ Res. 2013;5(5):120-124. doi:10.7813/2075-4124.2013/5-5/A.16 CR - Minas A, Mahmoudabadi S, Gamchi NS, Antoniassi MP, Alizadeh A, Bertolla, RP. Testicular torsion in vivo models: mechanisms and treatments. Andrology. 2023;11(7):1267-1285. doi:10.1111/andr.13418 CR - Shakeri R, Kheirollahi A, Davoodi J. Apaf-1: Regulation and function in cell death. Biochimie. 2017;135:111-125. doi:10.1016/j.biochi.2017.02.001 CR - Aşır F, Özgökce Ç. Momordica charantia reduced ovarian ischemia-reperfusion injury by suppressing APAF-1 expression. Eur Rev Med Pharmacol Sci. 2023;27(6):2182-2188. doi:10.26355/eurrev_202303_31751 CR - Baş H, Kara Ö, Kara M, Pandir D. Protective effect of vardenafil on ischemia–reperfusion injury in rat ovary. Turkish J Med Sci. 2013;43(5):684-689. doi:10.3906/sag-1207-108 CR - Bektas S, Karakaya K. Can M, et al. The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury. KJMS. 2016;32(7):339-347. doi:10.1016/j.kjms.2016.05.005 CR - Bozkurt M, Degirmentepe RB, Polat EC. et al. Protective effect of hydrogen sulfide on experimental testicular ischemia reperfusion in rats. J Pediatr Urol. 2020;16(1):40-e1. doi:10.1016/j.jpurol.2019.10.006 CR - Jo A, Denduluri S, Zhang B, et al. The versatile functions of Sox9 in development, stem cells, and human diseases. Genes & Diseases. 2014;1(2):149-161. doi:10.1016/j.gendis.2014.09.004 CR - Ramakrishnan AB, Burby PE, Adiga K, Cadigan KM. SOX9 and TCF transcription factors associate to mediate Wnt/β-catenin target gene activation in colorectal cancer. J Biol Chem. 2023;299(1):102735. doi:10.1016/j.jbc.2022.102735 CR - Ogawa Y, Terao M, Tsuji-Hosokawa A, Tsuchiya I, Hasegawa M, Takada S. SOX9 and SRY binding sites on mouse mXYSRa/Enh13 enhancer redundantly regulate Sox9 expression to varying degrees. Hum Mol Genet. 2023;32(1):55-64. doi:10.1093/hmg/ddac184 CR - McClelland K, Bowles J, Koopman P. Male sex determination: insights into molecular mechanisms. Asian J Androl. 2011;14(1):164. doi:10.1038/aja.2011.169 CR - Wright E, Hargrave MR, Christiansen J, et al. The Sry-related gene Sox9 is expressed during chondrogenesis in mouse embryos. Nature genetics. 1995;9(1):15-20. doi:10.1038/ng0195-15 CR - Da Silva SM, Hacker A, Harley, V, Goodfellow P, Swain A, Lovell-Badge R. Sox9 expression during gonadal development implies a conserved role for the gene in testis differentiation in mammals and birds. Nature genetics. 1996;14(1):62-68. doi:10.1038/ng0996-62 CR - Alzahrani FA. Melatonin improves therapeutic potential of mesenchymal stem cells-derived exosomes against renal ischemia-reperfusion injury in rats. Am J Trans Res. 2019;11(5):2887. doi:10.1111/iju.14345 CR - Chen JW, Huang MJ, Chen XN, et al. Transient upregulation of EGR1 signaling enhances kidney repair by activating SOX9+ renal tubular cells. Theranostics. 2022;12(12):5434. doi:10.7150/thno.73426 CR - Fan XD, Zheng HB, Fan XS, Lu S. Increase of SOX9 promotes hepatic ischemia/reperfusion (IR) injury by activating TGF-β1. Biochem Biophys Res Commun. 2018;503(1):215-221. doi:10.1016/j.bbrc.2018.06.005 CR - Lacraz GP, Junker JP, Gladka MM. et al. Tomo-Seq identifies SOX9 as a key regulator of cardiac fibrosis during ischemic injury. Circulation. 2017;136(15):1396-1409. doi:10.1161/CIRCULATIONAHA.117.027832 CR - Scharf GM, Kilian K, Cordero J. et al. Inactivation of Sox9 in fibroblasts reduces cardiac fibrosis and inflammation. JCI insight. 2019;4(15):e126721. doi:10.1172/jci.insight.126721 CR - El-Behery EI, El-Naseery NI, El-Ghazali HM., et al. The efficacy of chronic zinc oxide nanoparticles using on testicular damage in the streptozotocin-induced diabetic rat model. Acta Histochem. 2019;121(1):84-93. doi:10.1016/j.acthis.2018.10.010 CR - Chi A., Yang B, Cao X, et al. ICA II alleviates testicular torsion injury by dampening the oxidative and inflammatory stress. Front Endocrinol. 2022;13:871548. doi:10.3389/fendo.2022.871548 CR - Zhou L, Song K, Xu L. et al. Protective effects of uncultured adipose-derived stromal vascular fraction on testicular injury induced by torsion-detorsion in rats. Stem Cells Transl Med. 2019;8(4):383-391. doi:10.1002/sctm.18-00 UR - https://doi.org/10.30934/kusbed.1894271 L1 - https://dergipark.org.tr/en/download/article-file/5741817 ER -