Renal İskemi Reperfüzyonun İndüklediği Uzak Karaciğer Hasarında Koenzim Q10’un Koruyucu Etkisi

Abstract

Objectives: The aim of this study was to show the efficacy of coenzyme Q10, known as anti-oxidant with anti-inflammatory properties, in liver damage after renal ischemia-reperfusion (RIR). Materials and Methods: For this purpose, rats were divided into three groups to design an experimental RIR model. Group 1 rats were Sham group. Group 2 rats underwent RIR without any medication. Group 3 rats were given coenzyme Q10 before RIR. In order to evaluate the damage, serum urea, creatinine, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) andgamma glutamyl transferase (GGT) levels were investigated and additionally tissue (MPO), malondialdehyde (MDA), total sulfhydryl (SH), total nitrite and myeloperoxidase (MPO) levels were investigated. Histopathologic examination was performed for all groups and DNA fragmentation resulting from apoptotic fragmentation was evaluated with caspase-3 and TUNEL with immunohistochemical methods. Results: Urea and creatinine levels and also ALP, ALT, AST, GGT and LDH levels were significantly increased in group 2 compared to the Sham group. These increases were significantly lower in group 3. The tissue levels of MDA, nitrite, and MPO were significantly increased in group 2 compared to the Sham group, and SH levels were significantly decreased in group 2. In the group 3 rats, MDA, nitrite and MPO levels were decreased when compared to group 2. Additionally there was a significant increase in histopathologic scores in group 2 compared to the Sham group, whereas the decrease in histopathologic scores of group 3 was found to be significant when compared to group 2. Similarly, caspase-3 and TUNEL scores were significantly high in group 2 compared to Sham group and the scores were significantly low in group 3 compared to group 2. Conclusion: Coenzyme Q10 improved the histopathological findings, the serum tests and tissue oxidative stress levels in post-RIR liver tissues. Our results show that coenzyme Q10 can play an important role in protection of liver against RIR-induced damage.

Keywords

• Coenzyme Q10
• Renal Ischemia-reperfusion
• Distant Organ Injury
• Anti-oxidant
• Anti-inflammatory

Renal İskemi Reperfüzyonun İndüklediği Uzak Karaciğer Hasarında Koenzim Q10’un Koruyucu Etkisi

Abstract

Amaç: Bu çalışmanın amacı renal iskemi reperfüzyon (RIR) sonrası ortaya çıkan karaciğer hasarına karşı, anti-oksidan ve anti-enflamatuvar özellikleri bilinen koenzim Q10’un etkinliğini göstermektir. Gereç ve Yöntem: Deneysel RIR modeli oluşturulmak üzere sıçanlar üç gruba ayrıldı. Grup 1 sıçanlar Sham grubu olarak belirlendi. Grup 2 sıçanlara herhangi bir ilaç uygulanmadan RIR yapıldı. Grup 3 sıçanlara RIR öncesi koenzim Q10 verildi. Tüm gruplarda serumda üre, kreatinin, aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), alkalen fosfataz (ALP), laktat dehidrojenaz (LDH) ve gama-glutamil transferaz (GGT) değerlerine bakıldı. Oksidatif stres değerlendirmesi için karaciğer dokusunda malondialdehit (MDA), toplam sülfidril (SH), toplam nitrit (nitrit) ve miyeloperoksidaz (MPO) düzeyleri değerlendirildi. Tüm dokular patolojik olarak incelendi. İlave olarak kaspaz-3 ve TUNEL ile apopitotik parçalanma sonucu ortaya çıkan DNA fragmantasyonu histokimyasal olarak değerlendirildi. Bulgular: Üre ve kreatinin seviyelerinin yanı sıra ALP, ALT, AST, GGT ve LDH seviyeleri grup 2’de Sham grubuna göre anlamlı artış göstermiştir. Bu artış grup 3’te anlamlı olarak azalmaktadır. Doku testlerinden MDA, nitrit ve MPO düzeylerinde grup 2’de Sham grubuna göre anlamlı artış, SH düzeyi grup 2’de anlamlı azalış gözlenmektedir. Koenzim Q10 kullanan grupta ise grup 2 ile karşılaştırıldığında MDA, nitrit ve MPO düzeyleri azalmaktadır. Histopatolojik değerlendirmede grup 2 skorlarında, Sham grubu ile karşılaştırıldığında skorlamada anlamlı artış gözlendi. Ayrıca grup 3’te grup 2’ye göre histopatolojik skorlamadaki azalma anlamlı bulundu. Yine kaspaz-3 ve TUNEL boyanmalarında grup 2’de grup 1’e göre anlamlı artış gözlenirken, grup 3’te grup 2’ye göre anlamlı azalma izlenmektedir. Sonuç: Koenzim Q10 kullanımı ile RIR sonrası karaciğer dokularında gerek histopatolojik olarak ve gerekse serum testlerinde ve doku oksidatif stres düzeylerinde iyileşme gözlenmesi, koenzim Q10 kullanımının RIR sonrası gelişen karaciğer hasarına karşı korumada önemli bir rol oynayabileceğini göstermektedir.

Keywords

• Koenzim Q10
• Renal İskemi Reperfüzyon
• Uzak Organ Hasarı
• Anti-oksidan
• Anti-enflamatuvar

References

1. 1. Kelly KJ. Distant effects of experimental renal ischemia/reperfusion injury. J Am Soc Nephrol. 2003;14:1549-1558.
2. 2. Elapavaluru S, Kellum JA. Why do patients die of acute kidney injury? Acta Clin Belg. 2007;62:326-331.
3. 3. Ernster L, Forsmark-Andrée P. Ubiquinol: an endogenous antioxidant in aerobic organisms. Clin Investig. 1993;71:S60-S65.
4. 4. Folkers K. The potential of coenzyme Q 10 (NSC-140865) in cancer treatment. Cancer Chemother Rep 2. 1974;4:19-22.
5. 5. Fouad AA, Jresat I. Hepatoprotective effect of coenzyme Q10 in rats with acetaminophen toxicity. Environmental toxicology and pharmacology. Environ Toxicol Pharmacol. 2012;33:158-167.
6. 6. Vasiliev AV, Martinova EA, Sharanova NV, et al. Effects of coenzyme Q10 on rat liver cells under conditions of metabolic stress. Bulletin of experimental biology and medicine. Bull Exp Biol Med. 2011;150:416-419.
7. 7. Yokoyama H, Lingle DM, Crestanello JA, et al. Coenzyme Q10 protects coronary endothelial function from ischemia reperfusion injury via an antioxidant effect. Surgery. 1996;120:189-196.
8. 8. Mirmalek SA, Gholamrezaei Boushehrinejad A, Yavari H, et al. Antioxidant and anti-inflammatory effects of coenzyme Q10 on L-arginine-induced acute pancreatitis in rat. Oxid Med Cell Longev. 2016;2016:5818479.

9. 9. Liang S, Ping Z, Ge J. Coenzyme Q10 Regulates Antioxidative Stress and Autophagy in Acute Myocardial Ischemia-Reperfusion Injury Oxid Med Cell Longev. 2017;2017:9863181.
10. 10. Carrasco J, Anglada FJ, Campos JP, et al. The protective role of coenzyme Q 10 in renal injury associated with extracorporeal shockwave lithotripsy: a randomised, placebo‐controlled clinical trial. BJU Int. 2014;113:942-950.
11. 11. Fouad AA, Al-Sultan AI, Refaie SM, et al. Coenzyme Q10 treatment ameliorates acute cisplatin nephrotoxicity in mice. Toxicology. 2010;274:49- 56.
12. 12. Fatemikia H, Ketabchi F, Karimi Z, et al. Distant effects of unilateral renal ischemia/reperfusion on contralateral kidney but not lung in rats: the roles of ROS and iNOS. Can J Physiol Pharmacol. 2016;94:477-487.
13. 13. Detre S, Jotti GS, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48:876-878.
14. 14. Turbin DA, Leung S, Cheang MC, et al. Automated quantitative analysis of estrogen receptor expression in breast carcinoma does not differ from expert pathologist scoring: a tissue microarray study of 3,484 cases. Breast Cancer Res Treat. 2008;110:417-426.
15. 15. Wasowicz W, Nève J, Peretz A. Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage. Clin Chem. 1993;39:2522-2526.
16. 16. Bradley PP, Priebat DA, Christensen RD, et al. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. JInvest Dermatol. 1982;78:206-209.
17. 17. Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192-205.
18. 18. Smárason Jr A, Allman KG, Young D, et al. Elevated levels of serum nitrate, a stable end product of nitric oxide, in women with pre‐eclampsia. Br J Obstet Gynaecol. 1997;104:538-543.
19. 19. Lemasters JJ, Thurman RG. Reperfusion injury after liver preservation for transplantation. Annu Rev Pharmacol Toxicol. 1997;37:327-338.
20. 20. Neary P, Redmond H. Ischaemia-reperfusion injury and the systemic inflammatory response syndrome. Ischemia-Reperfusion Injury London: Blackwell Science. 1999:123-136.