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Karbon Tetraklorürün Neden Olduğu Akciğer Hasarında L-Karnitinin Antiapoptotik ve Histopatolojik Değişiklikler Üzerindeki Rolü

Year 2020, Volume: 17 Issue: 2, 189 - 194, 20.08.2020
https://doi.org/10.35440/hutfd.717101

Abstract

Amaç: Karbon Tetraklorür (CCl4) maruziyetinin akciğer üzerindeki toksik etkileri, bu toksik etkilere karşı L-karnitin'in koruyucu ve iyileştirici rolü ve kaspaz-3 aktivesinin değişiminin araştırılması amaçlanmıştır.
Materyal ve Metod: Çalışmada 25 adet sıçan her grupta 5 adet olacak şekilde 5 gruba ayrıldı. Deneyde yer alan gruplar şu şekilde oluşturuldu. Grup I: Kontrol grubu, 6 hafta boyunca haftada iki kez 0.2 ml zeytinyağı intraperitonal (ip) , Grup II: L-karnitin grubu, 6 hafta boyunca haftada iki kez 200 mg/kg L-karnitin (ip), Grup III: CCl4 grubu: 6 hafta boyunca haftada iki kez 0.2 ml /100 g CCl4 (ip), Grup IV: CCl4 + L-karnitin grubu, 6 hafta boyunca haftada iki kez CCl4 0.2 ml/100 g uygulamasından yarım saat sonra 200 mg/kg L-karnitin (ip), Grup V: L-karnitin + CCl4 grubu, 6 hafta boyunca haftada iki kez her 0.2 ml/100g CCl4 uygulamasından 24 saat önce 200 mg/kg L-karnitin (ip) verildi. Hem CCl4 hem de L-karnitin uygulamasına 6 hafta boyunca haftada iki kez devam edildi. Akciğer histopataolojisi değerlendirildi ve kaspaz-3enzim aktivitesi immunohistokimyasal yöntemle belirlendi. Kaspaz-3 immunpozitif hücre sayımı yapıldı.
Bulgular: CCl4 uygulanan grubunun akciğer dokusu histolojisinde belirgin fark gözlenmiştir. Alveolar intersitisiyel alanlarda artış, bronşiol epitelinde vakuolizasyon ve dejenerasyon gibi histopatolojik değişikliklere rastlanılmıştır. İstatistiksel analiz sonuçlarına göre Grup III ve V, kontrol grubuna göre anlamlı olarak yüksek bulunmuştur. L-karnitin CCl4 den önce verildiğinde kaspaz-3 hücre sayısı kontrol grubundan yüksekken, L-karnitin sonra verildiğinde kaspaz-3 hücre sayısının kontrol grubuna benzer şekilde olduğu görülmüştür
Sonuç: Sonuç olarak, alveolar hasar oluşumunda L-karnitin takviyesinin antiapoptotik etkisinin olduğu ve tedavi edici olarak kullanılmasının daha büyük önem taşıyacağını düşünmekteyiz.
Anahtar Kelimeler: Karbon Tetraklorür, Kaspaz-3, L-karnitin, Apoptoz.

Supporting Institution

Erciyes Üniversitesi BAP

Project Number

TSA-2018-8227

References

  • 1. Naz K, Khan MR, Shah NA, Sattar S, Noureen F, Awan ML. Pistacia chinensis: A potent ameliorator of CCl4 induced lung and thyroid toxicity in rat model. BioMed research international. 2014;2014:192906.
  • 2. Rahmouni F, Badraoui R, Amri N, Elleuch A, El-Feki A, Rebai T, et al. Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C. Toxicology mechanisms and methods. 2019;29(5):313-21.
  • 3. Manjrekar AP, Jisha V, Bag PP, Adhikary B, Pai M, Hegde A, et al. Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl 4 induced hepatotoxic rats. Indian J Exp Biol. 2008;46(7):514-20.
  • 4. Ganie SA, Haq E, Hamid A, Qurishi Y, Mahmood Z, Zargar BA, et al. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum. BMC complementary and alternative medicine. 2011;11(1):17.
  • 5. Khan RA. Protective effect of Launaea procumbens (L.) on lungs against CCl 4-induced pulmonary damages in rat. BMC complementary and alternative medicine. 2012;12(1):133.
  • 6. Ahmad B, Khan MR, Shah NA. Amelioration of carbon tetrachloride-induced pulmonary toxicity with Oxalis corniculata. Toxicology and industrial health. 2015;31(12):1243-51.
  • 7. Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, İlter K, Ersoy MA, et al. Deneysel karbon tetraklorür zehirlenmesinde akciğer doku hasarı ve melatonin hormonunun koruyucu rolü: Işık mikroskobik ve biyokimyasal bir çalışma. Düzce Tıp Fakültesi Dergisi. 2012;14(3):37-42.
  • 8. Kurt A, Tumkaya L, Yuce S, Turut H, Cure MC, Sehitoglu I, et al. The protective effect of infliximab against carbon tetrachloride-induced acute lung injury. Iranian journal of basic medical sciences. 2016;19(6):685.
  • 9. Ganie SA, Haq E, Masood A, Zargar MA. Amelioration of carbon tetrachloride induced oxidative stress in kidney and lung tissues by ethanolic rhizome extract of Podophyllum hexandrum in Wistar rats. Journal of Medicinal Plants Research. 2010;4(16):1673-7.
  • 10. Firat T, Ulas N, Terzi EH, Töre F, Kükner A. Deneysel Karaciger Hasarinin Akciger Dokusuna Etkisi ve Mast Hücrelerinin Rolü/The Effect of Experimental Liver Injury on Lung and Role of Mast Cells. Türkiye Klinikleri Tip Bilimleri Dergisi. 2013;33(4):1182.
  • 11. Mizuguchi S, Takemura S, Minamiyama Y, Kodai S, Tsukioka T, Inoue K, et al. S‐allyl cysteine attenuated CCl4‐induced oxidative stress and pulmonary fibrosis in rats. Biofactors. 2006;26(1):81-92.
  • 12. Yalcin A, Yumrutas O, Kuloglu T, Elibol E, Parlar A, Yilmaz İ, et al. Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury. Cellular and molecular biology Cellular and Molecular Biology. 2017.
  • 13. Obermayer-Straub P, Manns MP. Immunological mechanisms in liver injury. Drug-induced liver disease. 2002:125.
  • 14. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73(8):2013-26.
  • 15. Kawasaki M, Kuwano K, Hagimoto N, Matsuba T, Kunitake R, Tanaka T, et al. Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. The American journal of pathology. 2000;157(2):597-603.
  • 16. Xie J, Liu J, Chen T-M, Lan Q, Zhang Q-Y, Liu B, et al. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World Journal of Gastroenterology: WJG. 2015;21(18):5473.
  • 17. Kaya O, Koca YS, Barut I, Baspinar S, Sabuncuoglu MZ. L-carnitine reduces acute lung injury in experimental biliary obstruction. Saudi medical journal. 2015;36(9):1046.
  • 18. Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of L-carnitine. Biomed Pharmacother. 2014;68(5):631-9.
  • 19. Sener G, Paskaloglu K, Satiroglu H, Alican I, Kaçmaz A, Sakarcan A. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. Journal of cardiovascular pharmacology. 2004;43(5):698-705.
  • 20. Kelek SE, Afsar E, Akcay G, Danisman B, Aslan M. Effect of chronic L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in peripheral organs of adult Wistar rats. Food Chem Toxicol. 2019;134:110851.
  • 21. Yildirim AB, Ozdamar S, Yalcin B, Karabulut D. Changes in MAP-2 and GFAP immunoreactivity in pup hippocampus during prepubertal and pubertal periods caused by maternal subclinical hypothyroidism. Eur j anat. 2019:27-40.
  • 22. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Critical reviews in toxicology. 2003;33(2):105-36.
  • 23. Thrall KD, Vucelick ME, Gies RA, Benson J. Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. Journal of Toxicology and Environmental Health Part A. 2000;60(8):531-48.
  • 24. Kukner A, Tore F, Firat T, Terzi EH, Oner H, Balaban YH, et al. The preventive effect of low molecular weight heparin on CCL4-induced necrosis and apoptosis in rat liver. Annals of hepatology. 2010;9(4):445-54.
  • 25. Bahashwan S, Hassan MH, Aly H, Ghobara MM, El-Beshbishy HA, Busati I. Crocin mitigates carbon tetrachloride-induced liver toxicity in rats. Journal of Taibah university medical sciences. 2015;10(2):140-9.
  • 26. Sayan M, Karabulut D, Özdamar S. Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage. Journal of Biochemical and Molecular Toxicology. 2020:e22450.
  • 27. Ögetürk M, Çolakoğlu N, Kuş MA, Kuş İ, Sarsilmaz M. Karbon tetraklorür ile oluşturulan deneysel akciğer hasarında kafeik asit fenetil esterin koruyucu etkinliği. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2009;23(2):57-61.
  • 28. Miyamoto K. Experimental study on changes of the pulmonary vessels in the cirrhotic rats. Nihon Geka Gakkai zasshi. 1995;96(1):44-53.
  • 29. Surai PF. Antioxidant action of carnitine: molecular mechanisms and practical applications. EC Veterinary Science. 2015;2(1):66-84.
  • 30. Modanloo M, Shokrzadeh M. Analyzing Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis: Potential Role of L-carnitine. Iranian journal of kidney diseases. 2019;13(2):74.
  • 31. Thangasamy T, Jeyakumar P, Sittadjody S, Joyee AG, Chinnakannu P. L-carnitine mediates protection against DNA damage in lymphocytes of aged rats. Biogerontology. 2009;10(2):163-72.
  • 32. Demirdag K, Bahcecioglu IH, Ozercan IH, Ozden M, Yilmaz S, Kalkan A. Role of L‐carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. Journal of gastroenterology and hepatology. 2004;19(3):333-8.

The Role of L-Carnitine in Antiapoptotic and Histopathological Changes in Lung Injury İnduced by Carbon Tetrachloride

Year 2020, Volume: 17 Issue: 2, 189 - 194, 20.08.2020
https://doi.org/10.35440/hutfd.717101

Abstract

Background: The aim of this study to investigate the toxic effects of Carbon tetrachloride (CCl4) exposure on the lung, the protective and therapeutic role of L-carnitine against these toxic effects and the change of caspase-3 activity.
Materials and Methods: In the study, 25 rats were divided into 5 groups, with 5 in each group. Groups were created as follows. Group I: Control Group: 0.2 ml of olive oil twice a week for 6 weeks Intraperitoneal (ip); Group II: L-carnitine group, 200 mg/kg L-carnitine twice a week for 6 weeks (ip); Group III: CCl4 group: 0.2 ml/100 g CC14 twice a week for 6 weeks (ip); Group IV: CCI4 + L-carnitine group, 200 mg/kg L-carnitine half an hour after applying 0.2 ml/100 g CCl4 twice a week for 6 weeks (ip); Group V: L-carnitine + CCl4 group, 200 mg/kg L-carnitine 24 hours before 0.2 ml/100 g CCl4 application twice a week for 6 weeks (ip). Both CCl4 and L-carnitine administration was continued twice a week for 6 weeks. Lung histopathology was evaluated, and caspase-3 enzyme activity was determined by immunohistochemical method. Caspase-3 immunopositive cells were counted and statistical analysis was performed.
Results: An obvious difference was observed in the lung tissue histology of the CCl4 administered group. Histopathological changes such as increase in alveolar interstitial areas, vacuolization and degeneration in bronchiolar epithelium were encountered. According to the results of statistical analysis, Group III and Group V values were significantly higher than the control group. When L-carnitine was given before CCl4, the number of caspase-3 cells was higher than the control group. And when L-carnitine was given later than CCl4, the number of caspase-3 cells was similar with the control group.
Conclusion: As a result, we think that L-carnitine supplement has an anti-apoptotic effect and it can use as a therapeutic agent in alveolar damage formation.

Project Number

TSA-2018-8227

References

  • 1. Naz K, Khan MR, Shah NA, Sattar S, Noureen F, Awan ML. Pistacia chinensis: A potent ameliorator of CCl4 induced lung and thyroid toxicity in rat model. BioMed research international. 2014;2014:192906.
  • 2. Rahmouni F, Badraoui R, Amri N, Elleuch A, El-Feki A, Rebai T, et al. Hepatotoxicity and nephrotoxicity in rats induced by carbon tetrachloride and the protective effects of Teucrium polium and vitamin C. Toxicology mechanisms and methods. 2019;29(5):313-21.
  • 3. Manjrekar AP, Jisha V, Bag PP, Adhikary B, Pai M, Hegde A, et al. Effect of Phyllanthus niruri Linn. treatment on liver, kidney and testes in CCl 4 induced hepatotoxic rats. Indian J Exp Biol. 2008;46(7):514-20.
  • 4. Ganie SA, Haq E, Hamid A, Qurishi Y, Mahmood Z, Zargar BA, et al. Carbon tetrachloride induced kidney and lung tissue damages and antioxidant activities of the aqueous rhizome extract of Podophyllum hexandrum. BMC complementary and alternative medicine. 2011;11(1):17.
  • 5. Khan RA. Protective effect of Launaea procumbens (L.) on lungs against CCl 4-induced pulmonary damages in rat. BMC complementary and alternative medicine. 2012;12(1):133.
  • 6. Ahmad B, Khan MR, Shah NA. Amelioration of carbon tetrachloride-induced pulmonary toxicity with Oxalis corniculata. Toxicology and industrial health. 2015;31(12):1243-51.
  • 7. Gülcen B, Kuş MA, Çolakoğlu S, Ögetürk M, İlter K, Ersoy MA, et al. Deneysel karbon tetraklorür zehirlenmesinde akciğer doku hasarı ve melatonin hormonunun koruyucu rolü: Işık mikroskobik ve biyokimyasal bir çalışma. Düzce Tıp Fakültesi Dergisi. 2012;14(3):37-42.
  • 8. Kurt A, Tumkaya L, Yuce S, Turut H, Cure MC, Sehitoglu I, et al. The protective effect of infliximab against carbon tetrachloride-induced acute lung injury. Iranian journal of basic medical sciences. 2016;19(6):685.
  • 9. Ganie SA, Haq E, Masood A, Zargar MA. Amelioration of carbon tetrachloride induced oxidative stress in kidney and lung tissues by ethanolic rhizome extract of Podophyllum hexandrum in Wistar rats. Journal of Medicinal Plants Research. 2010;4(16):1673-7.
  • 10. Firat T, Ulas N, Terzi EH, Töre F, Kükner A. Deneysel Karaciger Hasarinin Akciger Dokusuna Etkisi ve Mast Hücrelerinin Rolü/The Effect of Experimental Liver Injury on Lung and Role of Mast Cells. Türkiye Klinikleri Tip Bilimleri Dergisi. 2013;33(4):1182.
  • 11. Mizuguchi S, Takemura S, Minamiyama Y, Kodai S, Tsukioka T, Inoue K, et al. S‐allyl cysteine attenuated CCl4‐induced oxidative stress and pulmonary fibrosis in rats. Biofactors. 2006;26(1):81-92.
  • 12. Yalcin A, Yumrutas O, Kuloglu T, Elibol E, Parlar A, Yilmaz İ, et al. Hepatoprotective properties for Salvia cryptantha extract on carbon tetrachloride-induced liver injury. Cellular and molecular biology Cellular and Molecular Biology. 2017.
  • 13. Obermayer-Straub P, Manns MP. Immunological mechanisms in liver injury. Drug-induced liver disease. 2002:125.
  • 14. Kerr JF, Winterford CM, Harmon BV. Apoptosis. Its significance in cancer and cancer therapy. Cancer. 1994;73(8):2013-26.
  • 15. Kawasaki M, Kuwano K, Hagimoto N, Matsuba T, Kunitake R, Tanaka T, et al. Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. The American journal of pathology. 2000;157(2):597-603.
  • 16. Xie J, Liu J, Chen T-M, Lan Q, Zhang Q-Y, Liu B, et al. Dihydromyricetin alleviates carbon tetrachloride-induced acute liver injury via JNK-dependent mechanism in mice. World Journal of Gastroenterology: WJG. 2015;21(18):5473.
  • 17. Kaya O, Koca YS, Barut I, Baspinar S, Sabuncuoglu MZ. L-carnitine reduces acute lung injury in experimental biliary obstruction. Saudi medical journal. 2015;36(9):1046.
  • 18. Tousson E, Hafez E, Zaki S, Gad A. P53, Bcl-2 and CD68 expression in response to amethopterin-induced lung injury and ameliorating role of L-carnitine. Biomed Pharmacother. 2014;68(5):631-9.
  • 19. Sener G, Paskaloglu K, Satiroglu H, Alican I, Kaçmaz A, Sakarcan A. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. Journal of cardiovascular pharmacology. 2004;43(5):698-705.
  • 20. Kelek SE, Afsar E, Akcay G, Danisman B, Aslan M. Effect of chronic L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in peripheral organs of adult Wistar rats. Food Chem Toxicol. 2019;134:110851.
  • 21. Yildirim AB, Ozdamar S, Yalcin B, Karabulut D. Changes in MAP-2 and GFAP immunoreactivity in pup hippocampus during prepubertal and pubertal periods caused by maternal subclinical hypothyroidism. Eur j anat. 2019:27-40.
  • 22. Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Critical reviews in toxicology. 2003;33(2):105-36.
  • 23. Thrall KD, Vucelick ME, Gies RA, Benson J. Comparative metabolism of carbon tetrachloride in rats, mice, and hamsters using gas uptake and PBPK modeling. Journal of Toxicology and Environmental Health Part A. 2000;60(8):531-48.
  • 24. Kukner A, Tore F, Firat T, Terzi EH, Oner H, Balaban YH, et al. The preventive effect of low molecular weight heparin on CCL4-induced necrosis and apoptosis in rat liver. Annals of hepatology. 2010;9(4):445-54.
  • 25. Bahashwan S, Hassan MH, Aly H, Ghobara MM, El-Beshbishy HA, Busati I. Crocin mitigates carbon tetrachloride-induced liver toxicity in rats. Journal of Taibah university medical sciences. 2015;10(2):140-9.
  • 26. Sayan M, Karabulut D, Özdamar S. Assessment of the protective and therapeutic effect of melatonin against thioacetamide‐induced acute liver damage. Journal of Biochemical and Molecular Toxicology. 2020:e22450.
  • 27. Ögetürk M, Çolakoğlu N, Kuş MA, Kuş İ, Sarsilmaz M. Karbon tetraklorür ile oluşturulan deneysel akciğer hasarında kafeik asit fenetil esterin koruyucu etkinliği. Fırat Üniversitesi Sağlık Bilimleri Tıp Dergisi. 2009;23(2):57-61.
  • 28. Miyamoto K. Experimental study on changes of the pulmonary vessels in the cirrhotic rats. Nihon Geka Gakkai zasshi. 1995;96(1):44-53.
  • 29. Surai PF. Antioxidant action of carnitine: molecular mechanisms and practical applications. EC Veterinary Science. 2015;2(1):66-84.
  • 30. Modanloo M, Shokrzadeh M. Analyzing Mitochondrial Dysfunction, Oxidative Stress, and Apoptosis: Potential Role of L-carnitine. Iranian journal of kidney diseases. 2019;13(2):74.
  • 31. Thangasamy T, Jeyakumar P, Sittadjody S, Joyee AG, Chinnakannu P. L-carnitine mediates protection against DNA damage in lymphocytes of aged rats. Biogerontology. 2009;10(2):163-72.
  • 32. Demirdag K, Bahcecioglu IH, Ozercan IH, Ozden M, Yilmaz S, Kalkan A. Role of L‐carnitine in the prevention of acute liver damage induced by carbon tetrachloride in rats. Journal of gastroenterology and hepatology. 2004;19(3):333-8.
There are 32 citations in total.

Details

Primary Language Turkish
Subjects Clinical Sciences
Journal Section Research Article
Authors

Ayşegül Burçin Yıldırım 0000-0001-7240-9997

Derya Karabulut This is me 0000-0003-2067-6174

Project Number TSA-2018-8227
Publication Date August 20, 2020
Submission Date April 9, 2020
Acceptance Date May 22, 2020
Published in Issue Year 2020 Volume: 17 Issue: 2

Cite

Vancouver Yıldırım AB, Karabulut D. Karbon Tetraklorürün Neden Olduğu Akciğer Hasarında L-Karnitinin Antiapoptotik ve Histopatolojik Değişiklikler Üzerindeki Rolü. Harran Üniversitesi Tıp Fakültesi Dergisi. 2020;17(2):189-94.

Harran Üniversitesi Tıp Fakültesi Dergisi  / Journal of Harran University Medical Faculty