Quercetin'in Sıçanlarda Alt Ekstremite İskemi Reperfüzyonu Sonrası Akciğer Hasarı Üzerindeki Etkilerinin Değerlendirilmesi
Year 2022,
Volume: 19 Issue: 2, 343 - 349, 28.08.2022
Yiğit Kılıç
,
Ayşegül Küçük
,
Mustafa Arslan
,
Mehmet Kirişçi
,
Abdullah Ozer
,
Tülay Mortaş
,
Gülay Kip
,
Levent Oktar
,
Mustafa Kavutcu
Abstract
Özet
Amaç: Quercetin antioksidan ve antiinflamatuar etkilere sahiptir. Literatürde daha önce Quercetin'in iskemi reperfüzyon hasarı üzerindeki etkisini araştıran hayvan deneyleri olmasına rağmen, alt ekstremite IR'nin uzak organ üzerindeki etkisini içeren çalışmalar nadirdir. Bu nedenle alt ekstremite iskemi reperfüzyon hasarı olan sıçanlarda Quercetin'in uzak organ (akciğer) üzerindeki koruyucu etkilerini araştırdık.
Materyal ve Metod: 18 adet erkek Wistar Albino rat, her grupta 6 adet olmak üzere rastgele 3 gruba ayrıldı; Kontrol (C), İskemi-reperfüzyon (IR), IR-Quercetin, (IR-Q). Ağırlıkları 200-250 gr arasındaydı. İşlemden 30 dakika önce intraperitoneal olarak 20 mg.kg-1 Quercetin verildi. iskemi reperfüzyon gruplarında infrarenal abdominal aorta atravmatik mikrovasküler klemp ile klemplendi. 120 dakika sonra klempi çıkardık ve 120 dakika daha reperfüzyon sağlandı. Reperfüzyon süresi sona erdiğinde akciğerlerden doku örnekleri alındı. Malondialdehit (MDA) düzeyi, süperoksit dismutaz (SOD) ve katalaz (CAT) enzim aktivitesi ve histopatolojik parametreler karşılaştırıldı.
Bulgular: İR grubunda MDA düzeyini kontrol grubuna göre daha yüksek bulduk (p<0,0001). IR-Q grubunda IR grubuna göre daha düşük MDA düzeyi bulundu (p=0.012). IR grubundaki SOD ve CAT enzim aktivitesi kontrol grubunda belirgin şekilde daha düşüktü (sırasıyla p<0.0001, p<0.001). IR-Q grubunda IR grubuna göre daha yüksek SOD ve CAT enzim aktiviteleri bulundu (sırasıyla p=0.012, p<0.001). Nötrofil infiltrasyonu/agregasyonu, alveolar duvar kalınlığı ve toplam akciğer hasarı skoru, IR grubunda C grubuna göre belirgin olarak daha yüksekti (sırasıyla p=0,001, p=0,002, p<0,0001). Ayrıca, Quercetin ile tedavi edilen grupta nötrofil infiltrasyonu/agregasyonu, alveolar duvar kalınlığı ve toplam akciğer hasarı skorunda IR grubuna göre istatistiksel olarak anlamlı bir düşüş gözlendi (sırasıyla p=0.023, p=0.022, p=0.002).
Sonuç: Ratlarda iskemiden 30 dakika önce 20 mg.kg-1 intraperitoneal olarak uygulanan Quercetin'in lipid peroksidasyonunu ve oksidatif stresi azalttığını ve akciğer histopatolojisinde IR'nin neden olduğu hasarı düzelttiğini belirledik. Quercetin'in IR öncesi uygulandığında akciğer koruyucu etkisi olduğunu düşünüyoruz. Çalışmanın bulguları diğer çalışmalarla desteklendiğinde Quercetin'in IR hasarı üzerindeki koruyucu etkilerinin detaylı olarak ortaya konacağını ve kullanım endikasyonlarının genişleyeceğini düşünüyoruz.
References
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Assessment of the Effects of Quercetin on Lung Injury After Hind Limb Ischemia Reperfusion in Rats
Year 2022,
Volume: 19 Issue: 2, 343 - 349, 28.08.2022
Yiğit Kılıç
,
Ayşegül Küçük
,
Mustafa Arslan
,
Mehmet Kirişçi
,
Abdullah Ozer
,
Tülay Mortaş
,
Gülay Kip
,
Levent Oktar
,
Mustafa Kavutcu
Abstract
Background: Quercetin has antioxidant and anti-inflammatory effects. Although there are previous animal experi-ments investigating Quercetin’s effect on ischemia reperfusion (IR) injury in the literature, studies involving effect of lower extremity IR on remote organ are rare.
Materials and Methods: 18 male Wistar Albino rats were randomly divided into 3 groups, 6 in each group as; Cont-rol (C), Ischemia-reperfusion (IR), IR-Quercetin, (IR-Q). Their weights were between 200-250 g. 30 minutes before the procedure20 mg/kgQuercetin was administered via intraperitoneal route. In the IR groups, infrarenal abdomi-nal aorta was clamped by an atraumatic microvascular clamp. After 120 minutes of ischemia and reperfusion was achieved for another 120 minutes. When reperfusion period ended, tissue samples were taken from the lungs. Malondialdehyde (MDA) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activity and histopathological parameters were compared.
Results: We found the MDA level in the IR group higher than the control group (p<0.0001). Lower MDA level was found in the IR-Q group compared tothe IR group (p=0.012). SOD and CAT enzyme activity in the IR group was notably lower in the control group (p<0.0001, p<0.001, respectively). Higher SOD and CAT enzyme activities were found in the IR-Q group compared to the IR group (p=0.012, p<0.001, respectively). Neutrophil infiltra-tion/aggregation, alveolar wall thickness and total lung injury score were notably higher in IR group than in C group (p=0.001, p=0.002, p<0.0001, respectively). In addition, a statistically significant decrease was observed in the Quercetin treated group in neutrophil infiltration/aggregation, alveolar wall thickness and total lung injury score compared to the IR group (p=0.023, p=0.022, p=0.002, respectively).
Conclusions: We determined that intraperitoneally administered Quercetin at a dose of 20 mg/kg30 minutes before ischemia in rats reduces lipid peroxidation, oxidative stress and reduces the damage caused by IR in lung histo-pathology.Study findings suggest that Quercetin has a lung protective effect when administered before IR.
References
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- Referans20. Kılıç Y, Özer A, Tatar T, Zor MH, Kirişçi M, Kartal H, et al. Effect of picroside II on hind limb ischemia reperfusion injury in rats. Drug Des Devel Ther. 2017 Jun 26;11:1917-1925. doi: 10.2147/DDDT.S132401. PMID: 28721011; PMCID: PMC5500556.
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- Referans23. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265-75. PMID: 14907713.
- Referans24. Aebi H. Catalase. In: H.U. Bergmeyer (Ed): Methods of Enzymatic Analysis, Academic Press, New York and London, 1974; pp.673-677.
- Referans25. Tuncay A, Sivgin V, Ozdemirkan A, Sezen SC, Boyunaga H, Kucuk A, et al. The Effect of Cerium Oxide on Lung Tissue in Lower Extremity Ischemia Reperfusion Injury in Sevoflurane Administered Rats. Int J Nanomedicine. 2020 Oct 6;15:7481-7489. doi: 10.2147/IJN.S263001. PMID: 33116483; PMCID: PMC7547779.
- Referans26. Akbas H, Ozden M, Kanko M, Maral H, Bulbul S, Yavuz S, et al. Protective antioxidant effects of carvedilol in a rat model of ischaemia-reperfusion injury. J Int Med Res. 2005 Sep-Oct;33(5):528-36. doi: 10.1177/147323000503300508. PMID: 16222886.
- Referans27. Abola MTB, Golledge J, Miyata T, Rha SW, Yan BP, Dy TC, et al. Asia-Pacific Consensus Statement on the Management of Peripheral Artery Disease: A Report from the Asian Pacific Society of Atherosclerosis and Vascular Disease Asia-Pacific Peripheral Artery Disease Consensus Statement Project Committee. J Atheroscler Thromb. 2020 Aug 1;27(8):809-907. doi: 10.5551/jat.53660. Epub 2020 Jul 4. Erratum in: J Atheroscler Thromb. 2020 Dec 1;27(12):1374. Erratum in: J Atheroscler Thromb. 2021;28(3):304. PMID: 32624554; PMCID: PMC7458790.
- Referans28. Harkin DW, Barros D'sa AA, McCallion K, Hoper M, Halliday MI, Campbell FC. Circulating neutrophil priming and systemic inflammation in limb ischaemia-reperfusion injury. Int Angiol. 2001 Mar;20(1):78-89. PMID: 11455935.
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