Ratlarda Deneysel Olarak Oluşturulan Renal İskemi-Reperfüzyon Hasarında Likopen ve Kafeinin Antioksidan Etkilerinin İncelenmesi

Abstract

Amaç: Renal iskemi/reperfüzyon hasarına maruz kalmış ratlarda likopen ve kafeinin antioksidan etkilerinin incelenmesi amaçlandı. Materyal ve Metod: Çalışmada kullanılan 200-250 gram Wistar albino cinsi erkek ratlara sağ renal nefroktomi sonrası 60 dk iskemi ve bunu takiben 60 dk reperfüzyon gerçekleştirildi. İskemiden 30 dk önce ratlara Likopen (5 mg/kg), kafein (50 mg/kg), Likopen (5 mg/kg) + kafein (50 mg/kg) intraperitoneal olarak uygulandı. Deney sonrası ratlardan 4 ml kan ve sol böbrek alındı. Biyokimyasal olarak doku malondialdehit, glutatyon peroksidaz, süperoksit dismutaz, serum kreatinin aktiviteleri ölçüldü ve histolojik olarak ışık mikroskobi bulguları değerlendirildi. Bulgular: Likopen ve kafeinin renal iskemi reperfüzyon hasarına karşı antioksidan etkisi diğer gruplarla karşılaştırıldığında likopenin serum kreatinin seviyelerinde anlamlı bir düşüş gözlenmiştir. Kafein ise yüksek çıkmakla birlikte anlamlı değildir. Gruplarda malondialdehit seviyeleri hasar grubuna göre düşük çıkmıştır, glutatyon peroksidaz ve süperoksit dismutaz ise yüksek olmasına rağmen anlamlılık gözlenmemiştir. Histopatolojik hasar; iskemi-reperfüzyon grubuyla karşılaştırıldığında diğer gruplarda anlamlı derecede düşük çıkmıştır. Likopen ve kafein; apoptozis, tübüler dilatasyon, tübüler epitel dejenerasyonu, glomerüler büzülme, deskuame epitel ve proteinöz kast miktarını önemli ölçüde düşürmüştür. Sonuç: Likopenin kafeine göre antioksidan etkinliği yüksek olmakla birlikte likopen ve kafeinin renal iskemi reperfüzyon hasarına karşı koruyucu etkisi vardır.

Keywords

• Böbrek
• İskemi-Reperfüzyon Hasarı
• Likopen
• Kafein

Project Number

2019.08.03.1413

Analysis of Antioxidant Effects of Lycopene and Caffeine in Experimentally Induced Renal Ischemia-Reperfusion Injury in Rats

Abstract

Background: The aim was to investigate the antioxidant effects of lycopene and caffeine in rats exposed to renal ischemia/reperfusion injury. Materials and Methods: Following right renal nephrectomy, 60 minutes of ischemia followed by 60 minutes of reperfusion were performed in 200-250 gram Wistar albino rats used in the study. 30 minutes before ischemia, lycopene (5 mg/kg), caffeine (50 mg/kg), lycopene (5 mg/kg) + caffeine (50 mg/kg) were administered intraperitoneally to the rats. After the experiment, 4 ml of blood and left kidney were taken from the rats. Tissue malondialdehyde, glutathione peroxidase, superoxide dismutase and serum creatinine activities were measured biochemically and light microscopy findings were evaluated histologically. Results: When the antioxidant effect of lycopene and caffeine against renal ischemia perfusion injury was compared with the other groups, a significant decrease was found in serum creatinine levels of lycopene. Caffeine was found to be high, but not statistically. malondialdehyde levels were lower in the groups than in the injury group; although glutathione peroxidase and superoxide dismutase were high, no significance was found. When compared with ischemia-reperfusion group, histopathological damage was found to be significantly lower than in the other groups. It was found that lycopene and caffeine reduced apoptosis, tubular dilatation, tubular epithelium degeneration, glomerular shrinkage, desquame epithelium and proteinaceous cast amount significantly. Conclusions: While lycopene has high antioxidant efficiency when compared with caffeine, lycopene and caffeine have protective effect against renal ischemia reperfusion injury.

Keywords

• Kidney
• Ischemia-Reperfusion Injury
• Lycopene
• Caffeine

Supporting Institution

Bolu Abant Izzet Baysal University Scientific Research Project

Project Number

2019.08.03.1413

References

1. Ahmadiasl N, Banaei S, Alihemmati A. Combination antioxidant effect of erythropoietin and melatonin on renal ischemia-reperfusion injury in rats. Iran J Basic Med Sci. 2013;16(12):1209–16.
2. Zhang X, Zhou X, Zhang Q, Zhu F. The preventive effects of dexmedetomidine against intestinal ischemia ‐ reperfusion injury in Wistar rats. 2015;18(6)604-9.
3. Zhou T, Prather ER, Garrison DE, Zuo L. Interplay between ROS and antioxidants during ischemia-reperfusion injuries in cardiac and skeletal muscle. Int J Mol Sci. 2018;19(2):417.
4. Chen X, Wang CC, Song SM, Wei SY, Li JS, Zhao SL, et al. The administration of erythropoietin attenuates kidney injury induced by ischemia/reperfusion with increased activation of Wnt/β-catenin signaling. J Formos Med Assoc. 2015;114(5):430–7.
5. Wang Y, Tian J, Qiao X, Su X, Mi Y, Zhang R, et al. Intermedin protects against renal ischemiareperfusion injury by inhibiting endoplasmic reticulum stress. BMC Nephrol [Internet]. 2015;16(1):1–12. Available from: http://dx.doi.org/10.1186/s12882-015-0157-7.
6. Sadıc M, Atılgan HI, Aydın A, Koca G, Korkmaz M, Karakan T, et al. Scintigraphic, histopathologic, and biochemical evaluation of lycopene effects on renal ischemia reperfusion injury in rats. Srp Arh Celok Lek. 2017;145(3–4):153–8.
7. Pektaş A, Gemalmaz H, Balkaya M, Ünsal C, Yenisey Ç, Kiliçarslan N, et al. The short-term protective effects of lycopene on renal ischemiareperfusion injury in rats. Turk Urol Derg. 2014;40(1):46–51.
8. Liu YE, Tong CC, Zhang YB, Jin HX, Gao Y, Hou MX. Effect of dexmedetomidine on rats with renal ischemia-reperfusion injury and the expression of tight junction protein in kidney. Int J Clin Exp Med. 2015;8(10):18751–7.

9. Zhao Y, Xin Z, Li N, Chang S, Chen Y, Geng L, et al. Nano-liposomes of lycopene reduces ischemic brain damage in rodents by regulating iron metabolism. Free Radic Biol Med. 2018;124:1–11.
10. Chen F, Sun ZW, Ye LF, Fu GS, Mou Y, Hu SJ. Lycopene protects against apoptosis in hypoxia/reoxygenationinduced H9C2 myocardioblast cells through increased autophagy. Mol Med Rep. 2015;11(2):1358–65.
11. Tong C, Peng C, Wang L, Zhang L, Yang X, Xu P, et al. Intravenous administration of lycopene, a tomato extract, protects against myocardial ischemia-reperfusion injury. Nutrients. 2016;8(3):1–13.
12. Yue R, Xia X, Jiang J, Yang D, Han Y, Chen X, et al. Mitochondrial DNA Oxidative Damage Contributes to Cardiomyocyte Ischemia/Reperfusion-Injury in Rats: Cardioprotective Role of Lycopene. J Cell Physiol. 2015;230(9):2128–41.
13. Lei X, Lei L, Zhang Z, Cheng Y. Neuroprotective effects of lycopene pretreatment on transient global cerebral ischemia-reperfusion in rats: The role of the Nrf2/HO-1 signaling pathway. Mol Med Rep. 2016;13(1):412–8.
14. Li XY, Xu L, Lin GS, Li XY, Jiang XJ, Wang T, et al. Protective effect of caffeine administration on myocardial ischemia/reperfusion injury in rats. Shock. 2011;36(3):289–94.
15. Chou WC, Kao MC, Yue CT, Tsai PS, Huang CJ. Caffeine Mitigates Lung Inflammation Induced by Ischemia-Reperfusion of Lower Limbs in Rats. Mediators Inflamm. 2015;2015.
16. Brezová V, Šlebodová A, Staško A. Coffee as a source of antioxidants: An EPR study. Food Chem. 2009;114(3):859–68.
17. Lee C. Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation. Clin Chim Acta. 2000;295(1–2):141–54.
18. Bayramoglu G, Bayramoglu A, Altuner Y, Uyanoglu M, Colak S. The effects of lycopene on hepatic ischemia/reperfusion injury in rats. Cytotechnology. 2015;67(3):487–91.
19. Schierwagen C, Bylund-Fellenius AC, Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharmacol Methods. 1990;23(3):179–86.
20. Li Y, Zhong D, Lei L, Jia Y, Zhou H, Yang B. Propofol prevents renal ischemia-reperfusion injury via inhibiting the oxidative stress pathways. Cell Physiol Biochem. 2015;37(1):14–26.
21. Sezen ŞC, Işik B, Bilge M, Arslan M, Çorau FM, Öztürk L, et al. Effect of dexmedetomidine on ischemiareperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemiareperfusion injury induced rats. Anaesthesia, Pain Intensive Care. 2016;20(2):143–9.
22. Assad OM, Aly Labib DA, Ahmed Rashed L. Dexmedetomidine protects against myocardial ischaemia/reperfusion-induced renal damage in rats. Egypt J Anaesth [Internet]. 2018;34(1):33–9. Available from: https://doi.org/10.1016/j.egja.2017.09.005
23. Kuhad A, Sethi R, Chopra K. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sci. 2008;83(3–4):128–34.
24. Zhang F, Xing S, Li Z. Antagonistic effects of lycopene on cadmium-induced hippocampal dysfunctions in autophagy, calcium homeostatis and redox. Oncotarget. 2017;8(27):44720–31.
25. Si YN, Bao HG, Xu L, Wang XL, Shen Y, Wang JS, et al. Dexmedetomidine protects against ischemia/reperfusion injury in rat kidney. Eur Rev Med Pharmacol Sci. 2014;18(13):1843–51.
26. Kaya C, Karabulut R, Turkyilmaz Z, Sonmez K, Kulduk G, Gülbahar Ö, et al. Lycopene has reduced renal damage histopathologically and biochemically in experimental renal ischemia-reperfusion injury. Ren Fail. 2015;37(8):1390–5.
27. Demir EO, Demirtaş CY, Paşaoğlu ÖT. Ratlarda böbrek antioksidan aktivitesi üzerine kafeinin etkileri. Turkish J Biochem. 2016;41(3):216–22.
28. Kosari S, Hemayat-talab R, Arab-ameri E, Keyhani F, Science S, Disorder H. Zahedan Journal of Research in Medical Sciences. 2013;55–8.
29. Kriško A, Kveder M, Pifat G. Effect of caffeine on oxidation susceptibility of human plasma low density lipoproteins. Clin Chim Acta. 2005;355(1–2):47–53.
30. Nikolic J, Bjelakovic G, Stojanovic I. Effect of caffeine on metabolism of L-arginine in the brain. Mol Cell Biochem. 2003;244(1–2):125–8.
31. Kilicdag H, Daglioglu YK, Erdogan S, Zorludemir S. Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury. J Matern Neonatal Med. 2014;27(14):1470–5.
32. Nilnumkhum A, Kanlaya R, Yoodee S, Thongboonkerd V. Caffeine inhibits hypoxia-induced renal fibroblast activation by antioxidant mechanism. Cell Adhes Migr [Internet]. 2019;13(1):260–72. Available from: https://doi.org/10.1080/19336918.2019.1638691
33. Fernández MJ, López A, Santa-Maria A. Apoptosis induced by different doses of caffeine on Chinese hamster ovary cells. J Appl Toxicol. 2003;23(4):221–4.
34. Al Moutaery K, Al Deeb S, Khan HA, Tariq M, Valadka AB, Narayan RK, et al. Caffeine impairs short-term neurological outcome after concussive head injury in rats. Neurosurgery. 2003;53(3):704–12.