Sıçan Testisinde CCL4-toksisitesine karşı L-Karnitin’in iNOS ve Apopitosis Üzerine Etkileri

Year 2025, Volume: 6 Issue: 2, 149 - 159, 29.07.2025

Derya Karabulut , Ayça Kara , Ali Tuğrul Akin , Tuğçe Merve Özyazgan , Murat Ünsal , Emin Kaymak

https://doi.org/10.46871/eams.1552827

Abstract

Amaç: Bu çalışmada CCL4-indüklenmiş testis hasarında L-karinitin’in koruyucu ve tedavi edici etkisinin araştırılması amaçlanmıştır.
Gereç ve Yöntem: Çalışmada 40 adet Sprague dawley cinsi erkek sıçan her grupta n=8 hayvan olacak şekilde 5 gruba ayrıldı. Grup 1: Kontrol; haftada 2 kez intraperitoneal (ip) 0,2 ml zeytinyağı uygulaması, Grup 2: L-karnitin; Haftada 2 kez 200 mg/kg L-karnitin (ip), Grup 3: CCL4; 6 hafta boyunca haftada 2 kez 0,2 ml CCL4 (ip), Grup 4: L-karnitin + CCL4 grubu, haftada 2 kez CCL4 uygulamasından 24 saat önce 200 mg/kg ip L-karnitin, Grup V: CCL4+ L-karnitin; haftada 2 kez CCL4 uygulamasından yarım saat sonra 200 mg/kg L-karnitin. Testis doku kesitlerinde histopatoloji, Johnsen’s testiküler biyopsi skoru (JTBS), seminifer tübül çap ölçümü, iNOS immünreaktivitesi ve apopitoz değerlendirildi.
Bulgular: Grup 1’e kıyasla Grup 3 doku kesitlerinin tamamında histolojik olarak bozulma, JTBS ve seminifer tübül çap ölçümünde azalma, artmış iNOS ekspresyonu ve apopitotik hücre gözlendi. L-karnitin uygulanan gruplarda bu parametrelerin tamamında düzeltici etki gösterdi.
Sonuç: L-karnitin CCL4 toksisitesine karşı dokuda hem koruyucu hem de iyileştirici etkiye sahiptir.

Keywords

Karbontetraklorid , L-karnitin , iNOS , testis.

Project Number

This work was supported by Erciyes University the Scientific Research Projects Unit, TSA-2018-8227 project code.

Effects of L-Carnitine on iNOS expression and Apoptosis in CCL4-induced Testicular damage in Rats

Abstract

Purpose: This study aimed to investigate the protective and therapeutic effects of L-carnitine in CCL4-induced testicular injury.
Methods: Forty male Sprague dawley rats were divided into 5 groups with (n = 8) animals in each group. Group I: Control group; 0.2 ml olive oil intraperitoneal (ip) twice weekly, Group II: L-carnitine group; 200 mg/kg L-carnitine (ip) twice a week, Group III: CCL4 group; 0.2 ml CCL4 (ip) twice a week for 6 weeks, Group IV: L-carnitine + CCL4 group, 200 mg/kg ip L-carnitine 24 hours before CCL4 twice a week, Group V: CCL4 + L-carnitine group; 200 mg/kg L-carnitine half an hour after CCL4 twice a week. The testicular tissue sections were evaluated histopathologically, Johnsen’s testicular biopsy score (JTBS), the mean seminiferous tubule diameter measurement, inducible nitric oxide synthase (iNOS) immunoreactivity and apoptosis (TUNEL).
Results: Compared to Group I, histological deterioration, decreased JTBS and MSTD, increased iNOS expression and apoptotic cells were observed in Group III tissue sections. All of these parameters showed corrective effects in L-carnitine applied groups.
Conclusion: L-carnitine has both protective and therapeutic effects against CCL4 toxicity.

Keywords

Carbontetrachloride , L-carnitine , iNOS , testis.

Ethical Statement

The research protocol with animal experimentation was approved by the Scientific Ethics Committee of Erciyes University (approval dated 04.04.2024, decision number 24/072).

Project Number

This work was supported by Erciyes University the Scientific Research Projects Unit, TSA-2018-8227 project code.

References

• 1.Rahmouni F, Daoud S, Rebai T. Teucrium polium attenuates carbon tetrachloride-induced toxicity in the male reproductive system of rats. Andrologia. 2019;51(2):e13182.
• 2. Khan RA. Protective effects of Launaea procumbens on rat testis damage by CCl4. Lipids in health and disease. 2012;11:103.
• 3. Kuloglu N, Sonmez MF. A biochemical and immunohistochemical study of the protective effects of carnosine for carbon tetrachloride induced liver injury in rats. Biotechnic & histochemistry : official publication of the Biological Stain Commission. 2015;90(8):608- 14.
• 4. Abdel Moneim AE. Prevention of carbon tetrachloride (CCl4)-induced toxicity in testes of rats treated with Physalis peruviana L. fruit. Toxicology and industrial health. 2016;32(6):1064-73.
• 5. Gao J, Qin XJ, Jiang H, Chen JF, Wang T, Zhang T, et al. Detecting serum and urine metabolic profile changes of CCl4-liver fibrosis in rats at 12 weeks based on gas chromatography-mass spectrometry. Experimental and therapeutic medicine. 2017;14(2):1496-504.
• 6. Ali SA, Faddah L, Abdel-Baky A, Bayoumi A. Protective effect of L-carnitine and coenzyme Q10 on CCl(4)-induced liver injury in rats. Scientia pharmaceutica. 2010;78(4):881-96.
• 7. Khalil I, Ghani M, Khan MR, Akbar F. Evaluation of biological activities and in vivo amelioration of CCl4 induced toxicity in lung and kidney with Abutilon pannosum (G.Forst.) Schltdl. in rat. Journal of ethnopharmacology. 2019:112395.
• 8. Sahreen S, Khan MR, Khan RA, Alkreathy HM. Cardioprotective role of leaves extracts of Carissa opaca against CCl4 induced toxicity in rats. BMC research notes. 2014;7:224.
• 9. El-Faras AA, Sadek IA, Ali YE, Khalil M, Mussa EB. Protective effects of Vitamin E onCCl4-induced testicular toxicity in male rats. Physiology international. 2016;103(2):157-68.
• 10. Berthelot P. Mechanisms and prediction of druginduced liver disease. Gut. 1973;14(4):332-9.
• 11. Sahreen S, Khan MR, Khan RA. Ameliorating effect of various fractions of Rumex hastatus roots against hepato- and testicular toxicity caused by CCl4. Oxidative medicine and cellular longevity. 2013;2013:325406.
• 12. Kılınç A, Oksit KKN. Biyolojik Fonksiyonları ve Toksik Etkileri. Ankara: Palme Yayıncılık. 2003:1-50.
• 13. Dixit VD, Parvizi N. Nitric oxide and the control of reproduction. Animal reproduction science. 2001;65(1-2):1-16.
• 14. Lowenstein CJ, Dinerman JL, Snyder SH. Nitric oxide: a physiologic messenger. Annals of internal medicine. 1994;120(3):227-37.
• 15. Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacological reviews. 1991;43(2):109-42.
• 16. Harmeyer J. The physiological role of Lcarnitine. Lohman Information. 2002;27:15-21.
• 17. Zhou X, Liu F, Zhai S. Effect of L-carnitine and/or L-acetyl-carnitine in nutrition treatment for male infertility: a systematic review. Asia Pacific journal of clinical nutrition. 2007;16:383.
• 18. Çekın AH, Gür G, Türkoğlu S, Aldemır D, Yilmaz U, Gürsoy M, et al. The protective effect of L-carnitine on hepatic ischemia-reperfusion injury in rats. Turk J Gastroenterol. 2013;24(1):51-6.
• 19. Li Y, Yang H. [Effect of interferon-α on rat liver fibrosis induced by CCl(4)]. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011;36(3):243-8.
• 20. Karabulut D, Akin AT, Unsal M, Lekesizcan A, Ozyazgan TM, Keti DB, et al. L-Carnitine ameliorates the liver by regulating alpha-SMA, iNOS, HSP90, HIF-1alpha, and RIP1 expressions of CCL4-toxic rats. Iran J Basic Med Sci. 2021;24(2):184-90.
• 21. 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.
• 22. Sonmez MF, Cilenk KT, Karabulut D, Unalmis S, Deligonul E, Ozturk I, et al. Protective effects of propolis on methotrexate-induced testis injury in rat. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2016;79:44- 51.
• 23. Szymonik-Lesiuk S, Czechowska G, Stryjecka- Zimmer M, Slomka M, Madro A, Celinski K, et al. Catalase, superoxide dismutase, and glutathione peroxidase activities in various rat tissues after carbon tetrachloride intoxication. Journal of hepato-biliary-pancreatic surgery. 2003;10(4):309-15.
• 24. Bayatli F, Akkus D, Kilic E, Saraymen R, Sonmez MF. The protective effects of grape seed extract on MDA, AOPP, apoptosis and eNOS expression in testicular torsion: an experimental study. World journal of urology. 2013;31(3):615-22.
• 25. Akram W, Syed M, Faruqi NA. Histopathological and Histomorphometric studies on the effects of Olanzapine on Testis: An experimental study in Albino Rats. Journal of the Anatomical Society of India. 2019;68(3):196.
• 26. Mardanshahi T, Rezaei N, Zare Z, Malekzadeh Shafaroudi M, Mohammadi H. Effects of LCarnitine on the sperm parameters disorders, apoptosis of spermatogenic cells and testis histopathology in diabetic Rats. International journal of reproductive biomedicine (Yazd, Iran). 2019;17(5).
• 27. Bogdan C. Nitric oxide and the immune response. Nature immunology. 2001;2(10):907- 16.
• 28. Nathan C, Xie Q. Regulation of biosynthesis of nitric oxide. Journal of Biological Chemistry. 1994;269(19):13725-8.
• 29. Khushboo M, Murthy MK, Devi MS, Sanjeev S, Ibrahim KS, Kumar NS, et al. Testicular toxicity and sperm quality following copper exposure in Wistar albino rats: ameliorative potentials of Lcarnitine. Environmental science and pollution research international. 2018;25(2):1837-62.
• 30. Kazemi-Darabadi S, Asadpour R, Shahbazfar AA, Alizadeh S. Effects of L-carnitine and betamethasone on ischemia-reperfusion injuries and sperm parameters following testicular torsion in a rat model. Veterinary research forum :an international quarterly journal 2019; 10(2):125-32.
• 31. Abdel Aziz RL, Abdel-Wahab A, Abo El-Ela FI, Hassan NEY, El-Nahass ES, Ibrahim MA, et al. Dose- dependent ameliorative effects of quercetin and l-Carnitine against atrazineinduced reproductive toxicity in adult male Albino rats. Biomedicine & Pharmacotherapy= 2018;102:855-64.