Rat Testis Torsiyon-Detorsiyon Hasarı Modelinde Silymarinin Antioksidan ve Anti-İnflamatuar Özelliklerinin Değerlendirilmesi

Abstract

Amaç: Testis torsiyonu, zamanında müdahale edilmediğinde infertilite ile sonuçlanabilecek ürolojik bir acil durumdur. Bu çalışma, bitki kaynaklı bir flavonoid olan ve antioksidan ile anti-inflamatuar etkileri bilinen silymarinin (SIL), testiküler torsiyon-detorsiyon (T/D) ilişkili iskemi-reperfüzyon (İ/R) hasar rat modelindeki koruyucu rolünü araştırmıştır. Gereç ve Yöntemler: Yirmi dört erkek Wistar albino sıçanı rastgele üç gruba ayrıldı: sham, T/D ve 100 mg/kg SIL. T/D ve SIL gruplarına 2 saat torsiyon, ardından 2 saat detorsiyon uygulandı. Testis doku örneklerinde oksidatif stres belirteçleri (malondialdehit (MDA), total oksidan düzeyi (TOS), miyeloperoksidaz (MPO) ve oksidatif stres indeksi (OSI)), antioksidan aktivite (total antioksidan düzeyi (TAS) ve süperoksit dismutaz (SOD)) ve proinflamatuar sitokinler (interlökin 1-beta (IL-1β) ve tümör nekroz faktör-alfa (TNF-α)) analiz edildi. Bulgular: SIL tedavisi, T/D grubuna kıyasla MDA, TOS, MPO, TNF-α, OSI ve IL-1β düzeylerini anlamlı şekilde azaltırken, SOD ve TAS düzeylerini anlamlı olarak artırdı (p<0.05). Bu da oksidatif ve inflamatuar hasarın azaltıldığını göstermektedir. Sonuç: Elde edilen sonuçlar, SIL’in T/D kaynaklı testiküler hasarda antioksidan ve anti-inflamatuar mekanizmalar yoluyla koruyucu etkiler sağladığını ve doğal bir tedavi adayı olabileceğini göstermektedir.

Keywords

• Testis torsiyonu-detorsiyonu
• Silymarin
• İskemi-reperfüzyon hasarı
• Rat modeli

Evaluation of Silymarin’s Antioxidant and Anti-Inflammatory Properties in Testicular Torsion-Detorsion Injury Rat Model

Abstract

Objective: Testicular torsion represents a urological emergency that, if unaddressed, can culminate in infertility. This study investigated the protective role of silymarin (SIL), a plant-derived flavonoid known for its antioxidant and anti-inflammatory effects, in a rat model of testicular torsion-detorsion (T/D)-associated ischemia-reperfusion (I/R) injury. Materials and Methods: Twenty-four male Wistar albino rats were randomized into three groups: sham, T/D, and 100 mg/kg SIL. The T/D and SIL groups underwent 2 hours of torsion followed by 2 hours of detorsion. Testicular tissue samples were analyzed for markers of oxidative stress (malondialdehyde (MDA), total oxidant status (TOS), myeloperoxidase (MPO), and oxidative stress index (OSI)), antioxidant activity (total antioxidant status (TAS) and (superoxide dismutase (SOD)), and proinflammatory cytokines (interleukin 1-beta (IL-1β and tumor necrosis factor- alpha (TNF-α)). Results: SIL treatment significantly diminished MDA, TOS, MPO, TNF-α, OSI, and IL-1β, and increased SOD and TAS in comparison to the T/D group (p<0.05), implying a mitigation of oxidative and inflammatory damage. Conclusion: The findings indicate that SIL confers protective benefits in T/D-induced testicular injury through its antioxidant and anti-inflammatory mechanisms, making it a promising natural candidate.

Keywords

• Testicular torsion-detorsion
• Silymarin
• Ischemia-reperfusion injury
• Rat model

References

1. Jacobsen FM, Rudlang TM, Fode M, Østergren PB, Sønksen J, Ohl DA. The impact of testicular torsion on testicular function. The world journal of men's health. 2020;38(3):298.
2. Nguyen HT, Rossini G. Hernia, hydrocele, testicular torsion, and varicocele. The Kelalis--King--Belman Textbook of Clinical Pediatric Urology: CRC Press; 2018. p. 1313–33.
3. Fehér ÁM, Bajory Z. A review of main controversial aspects of acute testicular torsion. Journal of Acute Disease. 2016;5(1):1–8.
4. Gazia MA. Histological Study on the Possible Ameliorating Effect of Platelet Rich Plasma on Ischemia/Reperfusion Injury in Testicular Torsion Model in Adult Albino Rat. Egyptian Journal of Histology. 2020;43(2):614–29.
5. Feng S, Yang H, Lou Y, Ru W, Wang A, Liu W. Clinical Characteristics of Testicular Torsion and Identification of Predictors of Testicular Salvage in Children: A Retrospective Study in a Single Institution. Urol Int. 2020;104(11-12):878–83.
6. Sögütçü Nn, Yokus B. Effects of gallic acid on ischemia-reperfusion induced testicular injury in a rat testicular torsion model. Analytical and Quantitative Cytopathology and Histopathology. 2021;43(1):1–7.
7. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of ischemia/reperfusion injury. Int Rev Cell Mol Biol. 2012;298:229–317.
8. Sarikaya K, Kölükçü E, Unsal V, Özdemir S. Protective Effects of Syringic Acid on Ischemia-Reperfusion Injury in Testicular Torsion: An Experimental Study in a Rat Model. Cureus. 2023;15(7).

9. Tvrdá E, Ďuračka M, Ivanišová E. Natural Biomolecules, Plant Extracts and Molecular Hydrogen-New Antioxidant Alternatives in the Management of Male Infertility. Molecular Hydrogen in Health and Disease: Springer; 2024. p. 359–84.
10. Li X, Zhang B, Yang H, Zhang L, Lou H, Zheng S. The emergence of natural products as potential therapeutics for male infertility. Andrology. 2024.
11. Fallah M, Davoodvandi A, Nikmanzar S, Aghili S, Mirazimi SMA, Aschner M. Silymarin (milk thistle extract) as a therapeutic agent in gastrointestinal cancer. Biomedicine & Pharmacotherapy. 2021;142:112024.
12. Soleimani V, Delghandi PS, Moallem SA, Karimi G. Safety and toxicity of silymarin, the major constituent of milk thistle extract: An updated review. Phytotherapy research. 2019;33(6):1627–38.
13. Ivanov V, Dyankova S, Pavlova M. Comparative study of the antioxidant properties of Silymarin and Milk Thistle Extracts. Trakia Journal of Sciences. 2021;19(1):1–6.
14. Viktorova J, Stranska-Zachariasova M, Fenclova M, Vitek L, Hajslova J, Kren V. Complex evaluation of antioxidant capacity of milk thistle dietary supplements. Antioxidants. 2019;8(8):317.
15. Rasul A, Akhtar N, Khan BA, Mahmood T, Zaman S, Atif A. Assessment of anti erythmic and skin whitening effects of milk thistle extract. African Journal of Pharmacy and Pharmacology. 2011;5(20):2306–9.
16. Ekinci Akdemir FN, Güler MC, Eraslan E, Tanyeli A, Yildirim S. Caftaric acid attenuates kidney and remote organ damage induced by renal ischemia-reperfusion injury. Sci Rep. 2024;14(1):31385.
17. Ekinci Akdemir FN, Tanyeli A, Güler MC, Eraslan E, Özbek Şebin S, Bircan B. Potential Beneficial Effects of Apelin-13 on Testicular Ischemia/Reperfusion Injury. New Trends in Medicine Sciences. 2024;5(2):98–103.
18. Tanyeli A, Öztürk D, Güzel D, Güler MC, Eraslan E, Baylan H. The Effects of Myricetin Against Testicular and Lung Injury Induced by Testicular Ischemia Reperfusion Model. Sakarya Tıp Dergisi. 2021;11(1):109–14.
19. Tanyeli A, Eraslan E, Güler MC, Ekinci Akdemir FN, Güzel Akdoğan D, Topdağı Ö. Investigation of the Effects of Maresin-1 on Testicular Ischemia Reperfusion Induced Oxidative Stress. Southern Clinics of Istanbul Eurasia. 2020;31(3):187–91.
20. Ersen E, Fazile Nur EA, Mustafa CANG, Derya GÜ ZELE, Elif P, Ömer T. Cryptotanshinone mitigates ischemia reperfusion-induced testicular damage: A experimental study. Annals of Medical Research. 2019;26(11):2549–52.
21. Hirayama K, Oshima H, Yamashita A, Sakatani K, Yoshino A, Katayama Y. Neuroprotective effects of silymarin on ischemia-induced delayed neuronal cell death in rat hippocampus. Brain Research. 2016;1646:297–303.
22. Yardım A, Kucukler S, Özdemir S, Çomaklı S, Caglayan C, Kandemir FM. Silymarin alleviates docetaxel-induced central and peripheral neurotoxicity by reducing oxidative stress, inflammation and apoptosis in rats. Gene. 2021;769:145239.
23. Akdemir FNE, Güler MC, Eraslan E, Tanyeli A, Yildirim S. Assessment of sinapic acid’s protective effects against ethanol-induced gastric ulcers in rats. Naunyn-Schmiedeberg's Archives of Pharmacology. 2024.
24. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry. 1979;95(2):351–8.
25. Demirdaş E, Arslan G, Kartal H, Erol G, Özdem T, Yavuz BB. Melatonin as a shield against skeletal muscle damage: A study on ischemia-reperfusion injury. Ulus Travma Acil Cerrahi Derg. 2025;31(2):103–11.
26. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update. Molecules. 2023;28(16):5979.
27. Lin W, Chen H, Chen X, Guo C. The Roles of Neutrophil-Derived Myeloperoxidase (MPO) in Diseases: The New Progress. Antioxidants. 2024;13(1):132.
28. Ahmad Jamil H, Abdul Karim N. Unraveling Mitochondrial Reactive Oxygen Species Involvement in Psoriasis: The Promise of Antioxidant Therapies. Antioxidants [Internet]. 2024; 13(10).
29. Strycharz-Dudziak M, Kiełczykowska M, Drop B, Świątek Ł, Kliszczewska E, Musik I. Total Antioxidant Status (TAS), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) in Oropharyngeal Cancer Associated with EBV Infection. Oxid Med Cell Longev. 2019;2019:5832410.
30. Zhou L, Feng JT, Zhang L, Kuang Y. Clinical significance of serum total oxidant/antioxidant status for the disease activity in active rheumatoid arthritis. Int J Clin Exp Pathol. 2017;10(8):8895–900.
31. Wang Y, Che M, Xin J, Zheng Z, Li J, Zhang S. The role of IL-1β and TNF-α in intervertebral disc degeneration. Biomedicine & Pharmacotherapy. 2020;131:110660.
32. Zhao Y, Zhou Y, Gong T, Liu Z, Yang W, Xiong Y. The clinical anti-inflammatory effects and underlying mechanisms of silymarin. iScience. 2024;27(11):111109.
33. Taleb A, Ahmad KA, Ihsan AU, Qu J, Lin N, Hezam K. Antioxidant effects and mechanism of silymarin in oxidative stress induced cardiovascular diseases. Biomedicine & Pharmacotherapy. 2018;102:689–98.
34. Surai PF, Surai A, Earle-Payne K. Silymarin and Inflammation: Food for Thoughts. Antioxidants. 2024;13(1):98.
35. Jin Y, Zhao X, Zhang H, Li Q, Lu G, Zhao X. Modulatory effect of silymarin on pulmonary vascular dysfunction through HIF-1α-iNOS following rat lung ischemia-reperfusion injury. Experimental and therapeutic medicine. 2016;12(2):1135–40.
36. Moghaddam AH, Sangdehi SRM, Ranjbar M, Hasantabar V. Preventive effect of silymarin-loaded chitosan nanoparticles against global cerebral ischemia/reperfusion injury in rats. European Journal of Pharmacology. 2020;877:173066.
37. Akbari-Kordkheyli V, Abbaszadeh-Goudarzi K, Nejati-Laskokalayeh M, Zarpou S, Khonakdar-Tarsi A. The protective effects of silymarin on ischemia-reperfusion injuries: A mechanistic review. Iranian Journal of Basic Medical Sciences. 2019;22(9):968.
38. Hao S, Lv Y, Wang Y, Liu K, Yu X, Tan M. Potential benefits of orally deliverable silymarin-loaded spirulina platensis in mitigating alcoholic liver disease. Food Research International. 2025;212:116508.
39. Akhigbe RE, Adekunle AO, Ajao MD, Sunmola TA, Aboyeji DO, Adegbola CA. Silymarin attenuates post-weaning bisphenol A-induced renal injury by suppressing ferroptosis and amyloidosis through Kim-1/Nrf2/HO-1 signaling modulation in male Wistar rats. Biochemical and Biophysical Research Communications. 2025;758:151668.
40. Lei X-y, Wang X, Cao X, Li Y-h. Silymarin mediates the gut-liver axis pathway to alleviate Carassius auratus hepatic lipid metabolism disorders caused by carbonate exposure. Comparative Biochemistry and Physiology Part D: Genomics and Proteomics. 2025;55:101457.
41. Kazak F, Akcakavak G, Alakus I, Alakus H, Kirgiz O, Karatas O. Proanthocyanidin alleviates testicular torsion/detorsion-induced ischemia/reperfusion injury in rats. Tissue and Cell. 2024;89:102459.
42. Khezri MR, Ghasemnejad-Berenji H, Ghasemnejad-Berenji M. Protective effects of empagliflozin on testicular injury induced by torsion/detorsion in adult male rats. Journal of Pediatric Urology. 2023;19(5):545.e1–.e7.
43. Yilmaz N, Hudaykulıyeva J, Gul S. Phoenixin-14 may ameliorate testicular damage caused by torsion-detorsion by reducing oxidative stress and inflammation in prepubertal rats. Tissue and Cell. 2024;88:102405.
44. Jafari A, Ghasemnejad-Berenji H, Nemati M, Pashapour S, Sadeghpour S, Ghasemnejad-Berenji M. Beneficial effects of memantine on ischemia/reperfusion injury following torsion/detorsion induced testicular damage in rats: Improvement in histological and biochemical parameters. Journal of Pediatric Urology. 2021;17(4):441.e1–.e7.