Sıçan Testisinde CCL4-toksisitesine karşı L-Karnitin’in iNOS ve Apopitosis Üzerine Etkileri
Yıl 2025,
Cilt: 6 Sayı: 2, 149 - 159, 29.07.2025
Derya Karabulut
,
Ayça Kara
,
Ali Tuğrul Akin
,
Tuğçe Merve Özyazgan
,
Murat Ünsal
,
Emin Kaymak
Öz
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.
Proje Numarası
This work was supported by Erciyes University the Scientific Research Projects Unit, TSA-2018-8227 project code.
Kaynakça
-
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.
Effects of L-Carnitine on iNOS expression and Apoptosis in CCL4-induced Testicular damage in Rats
Yıl 2025,
Cilt: 6 Sayı: 2, 149 - 159, 29.07.2025
Derya Karabulut
,
Ayça Kara
,
Ali Tuğrul Akin
,
Tuğçe Merve Özyazgan
,
Murat Ünsal
,
Emin Kaymak
Öz
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.
Etik Beyan
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).
Proje Numarası
This work was supported by Erciyes University the Scientific Research Projects Unit, TSA-2018-8227 project code.
Kaynakça
-
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.