Erkek Sıçanlarda Diklofenak Kaynaklı Testis Hasarı Üzerine Krisin’in İyileştirici Etkileri

Yıl 2022, Cilt: 11 Sayı: 4, 1484 - 1490, 22.12.2022

Cüneyt Çağlayan

Öz

Diklofenak, insanlarda ve hayvanlarda farklı patolojik durumlarla ilişkili akut ve kronik ağrıyı tedavi etmek için kullanılan bir anti-inflamatuar ilaçtır. Aşırı doz ve uzun süreli kullanımı hem insanlarda hem de sıçanlarda erkek üreme organı üzerinde olumsuz etkilere neden olmaktadır. Krisin; bal, propolis ve birçok bitki özünde yaygın olarak bulunan doğal bir fitokimyasaldır. Bu çalışma, erkek sıçanlarda diklofenak kaynaklı testis toksisitesine karşı krisinin koruyucu etkilerini araştırmak için yapıldı. Toplam 35 adet erkek sıçan sırasıyla i) kontrol, ii) krisin, iii) diklofenak, iv) diklofenak + krisin 25, v) diklofenak + krisin 50 grupları olmak üzere 5 gruba eşit olarak ayrıldı. Diklofenakın testis dokusunda kaspaz-3 ve Bcl-2 bağlı X proteini (Bax) gibi apoptotik parametrelerin mRNA transkript seviyelerini artırırken, B-hücreli lenfoma 2 (Bcl-2) mRNA transkript seviyesini azaltarak apoptoza neden olduğu tespit edildi. Ayrıca nükleer faktör eritroid 2 (Nrf-2) ve hem oksijenaz-1 (HO-1) gibi oksidatif stresle ilişkili markırların mRNA transkript seviyelerini azalttı. Yine matriks metalloproteinazların bir üyesi olan matriks metalloproteinaz-2 (MMP2) mRNA transkript seviyeleri diklofenak tarafından arttı. Buna karşın tedavi amacıyla verilen krisin’in yukarıda bahsi geçen parametrelerin seviyeleri üzerine olumlu etki göstererek oksidatif stres ve apoptozu azalttığı belirlendi. Sonuç olarak, bu çalışma krisin’in oksidatif stresi ve apoptozu azaltarak diklofenak kaynaklı testis toksisitesini hafifletebileceğini gösterdi.

Anahtar Kelimeler

Apoptoz, Diklofenak, Testis toksisitesi, Krisin Oksidatif stres

Destekleyen Kurum

Yok

Proje Numarası

-

Teşekkür

-

Healing Effects of Chrysin on Diclofenac-induced Testicular Damage in Male Rats

Öz

Diclofenac is an anti-inflammatory drug used to treat acute and chronic pain associated with different pathological conditions in humans and animals. Overdose and prolonged use cause adverse effects on the male reproductive organ in both humans and rats. Chrysin is a natural phytochemical commonly found in honey, propolis and many plant extracts. This study was conducted to investigate the protective effects of chrysin against diclofenac-induced testicular toxicity in male rats. A total of 35 male rats were divided equally into 5 groups as i) control, ii) chrysin, iii) diclofenac, iv) diclofenac + chrysin 25, v) diclofenac + chrysin 50 groups. It was determined that while diclofenac increased the mRNA transcript levels of apoptotic parameters such as caspase-3 and Bcl-2-associated X protein (Bax) in testis tissue, it caused apoptosis by decreasing the B-cell lymphoma 2 (Bcl-2) mRNA transcript level. It also reduced the mRNA transcript levels of markers associated with oxidative stress such as nuclear factor erythroid 2–related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1). Matrix metalloproteinase-2 (MMP2) mRNA transcript levels, also a member of matrix metalloproteinases, were increased by diclofenac. On the other hand, it was determined that chrysin given for treatment had a positive effect on the levels of the above-mentioned parameters and reduced oxidative stress and apoptosis. In conclusion, this study showed that chrysin can alleviate diclofenac-induced testicular toxicity by reducing oxidative stress and apoptosis.

Anahtar Kelimeler

Apoptosis, Chrysin, Diclofenac, Oxidative stress

Proje Numarası

-

Kaynakça

• 1. Soleimanpour, M, Imani, F, Safari, S, Sanaie, S, Soleimanpour, H, Ameli, H. and Alavian, S.M. (2016). "The Role of Non-steroidal Antiinflammatory Drugs (NSAIDS) in the Treatment of Patients with Hepatic Disease: A Review Article". Anesthesiology and Pain Medicine, 6 (4), e37822.
• 2. Walter, H.H. (2010). "Nonsteroidal Anti-Inflammatory Drugs and the Kidney". Pharmaceuticals, 3 (7), 2291-2321.
• 3. Adeyemi, W.J. and Olayaki, L.A. (2018). "Diclofenac–Induced Hepatotoxicity: Low Dose of Omega-3 Fatty Acids Have More Protective Effects". Toxicology Reports, 5, 90-95.
• 4. Simon, J.P. and Evan Prince, S. (2021). "Ameliorative Activity of Aqueous Leaf Extract From Madhuca Longifolia Against Diclofenac-Administered Toxicity on Rat Stomach and İntestine". Journal of Histotechnology, 44 (3), 114-126.
• 5. Owumi, S.E, Aliyu‐Banjo, N.O. and Odunola, O.A. (2020). "Selenium Attenuates Diclofenac‐Induced Testicular and Epididymal Toxicity in Rats". Andrologia, 52 (9), e13669.
• 6. Abiola, T.S, Adebayo, O.C. and Babalola, O.O. (2019). "Diclofenac-Induced Kidney Damage in Wistar Rats: Involvement of Antioxidant Mechanism". Journal of Biosciences and Medicines, 7 (12), 96832.
• 7. Benzer, F, Kandemir, F.M, Ozkaraca, M, Kucukler, S. and Caglayan, C. (2018). "Curcumin Ameliorates Doxorubicin‐Induced Cardiotoxicity By Abrogation of Inflammation, Apoptosis, Oxidative DNA Damage, and Protein Oxidation in Rats". Journal of Biochemical and Molecular Toxicology, 32 (2), e22030.
• 8. Kandemir, F.M, Kucukler, S, Eldutar, E, Caglayan, C. and Gülçin, İ. (2017). "Chrysin Protects Rat Kidney From Paracetamol-Induced Oxidative Stress, İnflammation, Apoptosis, and Autophagy: A Multi-Biomarker Approach". Scientia Pharmaceutica, 85 (1), 4.
• 9. Temel, Y, Kucukler, S, Yıldırım, S, Caglayan, C. and Kandemir, F.M. (2020). "Protective Effect of Chrysin on Cyclophosphamide-Induced Hepatotoxicity and Nephrotoxicity via The Inhibition of Oxidative Stress, Inflammation, and Apoptosis". Naunyn-Schmiedeberg's Archives of Pharmacology, 393 (3), 325-337.
• 10. Kucukler, S, Benzer, F, Yildirim, S, Gur, C, Kandemir, F.M, Bengu, A.S, Ayna, A, Caglayan, C. and Dortbudak, M.B. (2021). "Protective Effects of Chrysin Against Oxidative Stress and Inflammation Induced By Lead Acetate in Rat Kidneys: A Biochemical and Histopathological Approach". Biological Trace Element Research, 199 (4), 1501-1514.
• 11. Eldutar, E, Kandemir, F.M, Kucukler, S. and Caglayan, C. (2017). "Restorative Effects of Chrysin Pretreatment on Oxidant–Antioxidant Status, Inflammatory Cytokine Production, and Apoptotic and Autophagic Markers in Acute Paracetamol‐Induced Hepatotoxicity in Rats: An Experimental and Biochemical Study". Journal of Biochemical and Molecular Toxicology, 31 (11), e21960.
• 12. Prince, S.E. (2018). "Diclofenac-Induced Renal Toxicity in Female Wistar Albino Rats is Protected By The Pre-Treatment of Aqueous Leaves Extract of Madhuca Longifolia Through Suppression of Inflammation, Oxidative Stress and Cytokine Formation". Biomedicine and Pharmacotherapy, 98, 45-51.
• 13. Livak, K.J. and Schmittgen, T.D. (2001). "Analysis Of Relative Gene Expression Data Using Real-Time Quantitative PCR and The 2−ΔΔCT Method". Methods, 25, 402-408.
• 14. Elder, D.J, Halton, D.E, Hague, A. and Paraskeva, C, (1997). "Induction of Apoptotic Cell Death in Human Colorectal Carcinoma Cell Lines By A Cyclooxygenase-2 (COX-2)-Selective Nonsteroidal Anti-İnflammatory Drug: Independence From COX-2 Protein Expression". Clinical Cancer Research, 3 (10), 1679-1683.
• 15. Özdemir, S, Kucukler, S, Çomaklı, S. and Kandemir, F.M. (2020). "The Protective Effect of Morin Against Ifosfamide-Induced Acute Liver İnjury in Rats Associated with The Inhibition of DNA Damage and Apoptosis". Drug and Chemical Toxicology, 45 (3), 1308-1317.
• 16. Famurewa, A.C, Akunna, G.G, Nwafor, J, Chukwu, O.C, Egedigwe, C.A.E. and Oluniran, J.N. (2019). "Nephroprotective Activity of Virgin Coconut Oil on Diclofenac-Induced Oxidative Nephrotoxicity is Associated With Antioxidant and Antiinflammatory Effects in Rats". Avicenna Journal of Phytomedicine, 10 (3), 316-324.
• 17. Adeyemi, W.J. and Olayaki, L.A. (2018). "Diclofenac–Induced Hepatotoxicity: Low Dose of Omega-3 Fatty Acids Have More Protective Effects". Toxicology Reports, 5, 90-95.
• 18. Motawi, T.K, Ahmed, S.A, El-Boghdady, N.A, Metwally, N.S, and Nasr, N.N. (2019). "Protective Effects of Betanin Against Paracetamol and Diclofenac Induced Neurotoxicity and Endocrine Disruption in Rats". Biomarkers, 24 (7), 645-651.
• 19. Mogilner, J.G, Lurie, M, Coran, A.G, Nativ, O, Shiloni, E. and Sukhotnik, I. (2006). "Effect of Diclofenac on Germ Cell Apoptosis Following Testicular Ischemia-Reperfusion Injury in A Rat". Pediatric Surgery International, 22 (1), 99-105.
• 20. Çelik, H, Kucukler, S, Çomaklı, S, Caglayan, C, Özdemir, S, Yardım, A, Karaman, M. and Kandemir, F.M. (2020). "Neuroprotective Effect of Chrysin on Isoniazid-Induced Neurotoxicity via Suppression of Oxidative Stress, Inflammation and Apoptosis in Rats". Neurotoxicology, 81, 197-208.
• 21. Caglayan, C, Kandemir, F.M, Darendelioğlu, E, Küçükler, S. and Ayna, A. (2021). "Hesperidin Protects Liver and Kidney Against Sodium Fluoride-Induced Toxicity Through Anti-Apoptotic and Anti-Autophagic Mechanisms". Life Sciences, 281, 119730.
• 22. Kucukler, S, Caglayan, C, Darendelioğlu, E. and Kandemir, F.M. (2020). "Morin Attenuates Acrylamide-Induced Testicular Toxicity in Rats By Regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR Signaling Pathways". Life Sciences, 261, 118301.
• 23. Caglayan, C, Kandemir, F.M, Darendelioğlu, E, Yıldırım, S, Kucukler, S. and Dortbudak, M.B. (2019). "Rutin Ameliorates Mercuric Chloride-Induced Hepatotoxicity in Rats Via İnterfering With Oxidative Stress, İnflammation and Apoptosis". Journal of Trace Elements in Medicine and Biology, 56, 60-68.
• 24. Küçükler, S, Kandemir, F.M, Özdemir, S, Çomaklı, S. and Caglayan C. (2021). "Protective Effects of Rutin Against Deltamethrin-Induced Hepatotoxicity and Nephrotoxicity in Rats via Regulation of Oxidative Stress, Inflammation, and Apoptosis". Environmental Science and Pollution Research, 28, 62975-62990.
• 25. Kandemir, F.M, Yıldırım, S, Kucukler, S, Caglayan, C. Darendelioğlu, E. and Dortbudak, M.B. (2020). "Protective Effects of Morin Against Acrylamide-Induced Hepatotoxicity and Nephrotoxicity: A Multi-Biomarker Approach". Food and Chemical Toxicology, 138, 111190.
• 26. Porter, A.G. and Jänicke, R.U. (1999). "Emerging Roles of Caspase-3 in Apoptosis". Cell Death and Differentiation, 6 (2), 99-104.
• 27. Atagün, G, Zafer, E. ve Gürkanlı, İ. (2011). "Apoptoziste Mitokondrinin Rolü". Türk Bilimsel Derlemeler Dergisi, 4 (2), 49-53. 28. Kim, H.P, Wang, X, Lee, S.J, Huang, M.H, Wan, Y, Ryter, S.W. and Choi, A.M. (2008). "Autophagic Proteins Regulate Cigarette Smoke Induced Apoptosis: Protective Role of Heme Oxygenase-1". Autophagy, 4 (7), 887-895.
• 29. Çelik, H, Kandemir, F.M, Caglayan, C, Özdemir, S, Çomaklı, S, Kucukler, S. and Yardım, A. (2020). "Neuroprotective Effect of Rutin Against Colistin-Induced Oxidative Stress, Inflammation and Apoptosis in Rat Brain Associated With The CREB/BDNF Expressions". Molecular Biology Reports, 47 (3), 2023-2034.
• 30. Park, K.S, Kim, S.J, Kim, K.H. and Kim, J.C. (2011). "Clinical Characteristics of TIMP2, MMP2, and MMP9 Gene Polymorphisms in Colorectal Cancer". Journal of Gastroenterology and Hepatology, 26 (2), 391-397.
• 31. Yalcın, A. (2019). "The Effects of N-Acetylcysteine on MMP-2 and MMP-9 Immune Activities in Testicular Tissue of Streptezotocin Induced Diabetic Rats". Sakarya Tıp Dergisi, 9 (1), 59-67.
• 32. Yao, P.L, Lin, Y.C. and Richburg, J.H. (2009). "TNF Alpha-Mediated Disruption of Spermatogenesis in Response to Sertoli Cell Injury in Rodents is Partially Regulated By MMP2". Biology of Reproduction, 80 (3), 581-589.
• 33. Huyut, Z, Alp, H.H, Yaman, T, Keleş, Ö.F, Yener, Z, Türkan, F. and Ayengin, K. (2021). "Comparison of The Protective Effects of Curcumin and Caffeic Acid Phenethyl Ester Against Doxorubicin‐induced Testicular Toxicity. Andrologia, 53 (2), e13919.