Borat akciğer ve böbrekte deneysel supraçölyak aort klemplenmesine bağlı oksidatif stresi azaltır, ancak organ hasarını önlemekte yetersizdir
Amaç: Bu çalışmada sıçan modelinde 2-aminoetoksidifenil boratın (2-APB) aortik klemplenmeye bağlı akciğer ve böbrek dokusu oksidasyonu, doku enflamasyonu ve histolojik hasar üzerindeki etkileri araştırıldı. Çalışma planı: Toplam 28 erişkin dişi Wistar albino sıçan, rastgele dört eşit gruba ayrıldı: Kontrol grubu, iskemi-reperfüzyon grubu, dimetil sülfoksit grubu ve 2-APB grubu. Kontrol grubundaki hayvanlara medyan laparotomi yapıldı. Kalan gruplarda supraçölyak aort 45 dk. süreyle klemplendi ve ardından 60 dk. reperfüzyon oluşturuldu. Klemplemeden önce 2-APB (2 mg/kg) uygulandı. Diğer gruplarda hayvanlara salin (iskemi-reperfüzyon grubu) veya dimetil sülfoksit (dimetil sülfoksit grubu) verildi. Reperfüzyon sonunda böbrek ve akciğer doku örnekleri alındı. Bulgular: Aortun klemplenmesi, iskemi-reperfüzyon ve dimetil sülfoksit gruplarında dokudaki toplam oksidan statüsünün artmasına ve total antioksidan statüsünün ve glutatyon düzeylerinin azalmasına neden oldu. Doku interlökin-1 beta ve tümör nekroz faktör-alfa düzeyleri, nükleer faktör kappa beta aktivasyonu ve histolojik hasar şiddeti skorları da bu gruplarda daha yüksek bulundu. 2-APB tedavisi, toplam oksidan statüsündeki artışı ve total antioksidan statüsü ve glutatyon düzeylerindeki düşüşü ortadan kaldırdı. Ayrıca, interlökin-1 beta düzeylerinde anlamlı azalmaya neden oldu; ancak tümör nekroz faktör-alfa düzeylerini, nükleer faktör kappa beta aktivasyonunu ve histolojik hasar skorlarını önemli ölçüde değiştirmedi. Sonuç: Borat, sıçanlarda supraçölyak aortik klemplenmeye bağlı böbrek ve akciğer hasarında oksidatif stresi azaltarak faydalı bir antioksidan etki göstermiştir; ancak, nükleer faktör kappa beta aktivasyonunu inhibe etmemiş ve histolojik hasarı önleyememiştir.
Borate reduces experimental supra-celiac aortic clamping-induced oxidative stress in lung and kidney, but fails to prevent organ damage
Background: This study aims to investigate the effects of 2-aminoethoxydiphenyl borate (2-APB) on aortic clamping-induced lung and kidney tissue oxidation, tissue inflammation, and histological damage in a rat model. Methods: A total of 28 adult female Wistar albino rats were randomly allocated to four equal groups: Control group, ischemia-reperfusion group, dimethyl sulfoxide group, and 2-APB group. Animals in the control group underwent median laparotomy. In the remaining groups, supra-celiac aorta was clamped for 45 min and, then, reperfusion was constituted for 60 min. The 2-APB (2 mg/kg) was administered before clamping. The remaining groups received saline (ischemia-reperfusion group) or dimethyl sulfoxide (dimethyl sulfoxide group). Kidney and lung tissue samples were harvested at the end of reperfusion. Results: Aortic occlusion caused increased tissue total oxidant status and reduced total antioxidant status and glutathione levels in the ischemia-reperfusion and dimethyl sulfoxide groups. Tissue interleukin-1 beta and tumor necrosis factor-alpha levels, nuclear factor kappa beta activation, and histological damage severity scores were also higher in these groups. The 2-APB treatment eliminated the increase in total oxidant status and the decrease in total antioxidant status and glutathione levels. It also caused a decrease in the interleukin-1 beta levels, although it did not significantly alter the tumor necrosis factor-alpha levels, nuclear factor kappa beta immunoreactivity, and histological damage scores. Conclusion: Borate exerted a beneficial antioxidant effect as evidenced by reduced oxidative stress; however, it did not inhibit nuclear factor kappa beta activation and prevent histological damage in supra-celiac aortic clamping-induced kidney and lung injury in rats
___
- 1. İnce İ, Akar İ, Arıcı A. Renoprotective effect of edaravone in acute limb ischemia/reperfusion injury. Turk Gogus Kalp Dama 2020;28:274-81.
- 2. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB. Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 2014;20:1126-67.
- 3. Wu MY, Yiang GT, Liao WT, Tsai AP, Cheng YL, Cheng PW, et al. Current mechanistic concepts in ischemia and reperfusion injury. Cell Physiol Biochem 2018;46:1650-67.
- 4. Honda HM, Korge P, Weiss JN. Mitochondria and ischemia/ reperfusion injury. Ann N Y Acad Sci 2005;1047:248-58.
- 5. Koc ER, Gökce EC, Sönmez MA, Namuslu M, Gökce A, Bodur AS. Borax partially prevents neurologic disability and oxidative stress in experimental spinal cord ischemia/ reperfusion injury. J Stroke Cerebrovasc Dis 2015;24:83- 90.
- 6. Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol 2011;25:54-8.
- 7. Donoiu I, Militaru C, Obleagă O, Hunter JM, Neamţu J, Biţă A, et al. Effects of boron-containing compounds on cardiovascular disease risk factors - A review. J Trace Elem Med Biol 2018;50:47-56.
- 8. Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K. 2APB, 2-aminoethoxydiphenyl borate, a membrane- penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem 1997;122:498-505.
- 9. Karademir M, Gonul Y, Simsek N, Eser O. The neuroprotective effects of 2-APB in rats with experimentally- -induced severe acute pancreatitis. Bratisl Lek Listy 2018;119:752-6.
- 10. Nicoud IB, Knox CD, Jones CM, Anderson CD, Pierce JM, Belous AE, et al. 2-APB protects against liver ischemia- reperfusion injury by reducing cellular and mitochondrial calcium uptake. Am J Physiol Gastrointest Liver Physiol 2007;293:G623-30.
- 11. Yildar M, Aksit H, Korkut O, Ozyigit MO, Sunay B, Seyrek K. Protective effect of 2-aminoethyl diphenylborinate on acute ischemia-reperfusion injury in the rat kidney. J Surg Res 2014;187:683-9.
- 12. Basbug M, Yildar M, Yaman İ, Cavdar F, Özkan ÖF, Aksit H, et al. Effect of different doses of 2-aminoethoxydiphenyl borate on intestinal ischemia-reperfusion injury. Eur Surg 2017;49:32-7.
- 13. Taskin MI, Hismiogullari AA, Yay A, Adali E, Gungor AC, Korkmaz GO, et al. Effect of 2-aminoethoxydiphenyl borate on ischemia-reperfusion injury in a rat ovary model. Eur J Obstet Gynecol Reprod Biol 2014;178:74-9.
- 14. Koçarslan A, Koçarslan S, Aydin MS, Gunay Ş, Karahan MA, Taşkın A, et al. Intraperitoneal administration of silymarin protects end organs from multivisceral ischemia/ reperfusion injury in a rat model. Braz J Cardiovasc Surg 2016;31:434-9.
- 15. Galvao J, Davis B, Tilley M, Normando E, Duchen MR, Cordeiro MF. Unexpected low-dose toxicity of the universal solvent DMSO. FASEB J 2014;28:1317-30.
- 16. Syed M, Skonberg C, Hansen SH. Effect of some organic solvents on oxidative phosphorylation in rat liver mitochondria: Choice of organic solvents. Toxicol In Vitro 2013;27:2135-41.
- 17. Du K, Williams CD, McGill MR, Xie Y, Farhood A, Vinken M, et al. The gap junction inhibitor 2-aminoethoxy-diphenyl- borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation. Toxicol Appl Pharmacol 2013;273:484-91.
- 18. Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
- 19. Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 2004;37:277-85.
- 20. Aydin MS, Caliskan A, Kocarslan A, Kocarslan S, Yildiz A, Günay S, et al. Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/ reperfusion model in rat. Int J Surg 2014;12:601-5.
- 21. Kurtoglu T, Durmaz S, Akgullu C, Gungor H, Eryilmaz U, Meteoglu I, et al. Ozone preconditioning attenuates contrast- induced nephropathy in rats. J Surg Res 2015;195:604-11.
- 22. Li Z, Nickkholgh A, Yi X, Bruns H, Gross ML, Hoffmann K, et al. Melatonin protects kidney grafts from ischemia/ reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation. J Pineal Res 2009;46:365-72.
- 23. Song M, Xia B, Li J. Effects of topical treatment of sodium butyrate and 5-aminosalicylic acid on expression of trefoil factor 3, interleukin 1beta, and nuclear factor kappaB in trinitrobenzene sulphonic acid induced colitis in rats. Postgrad Med J 2006;82:130-5.
- 24. Morihara H, Obana M, Tanaka S, Kawakatsu I, Tsuchiyama D, Mori S, et al. 2-aminoethoxydiphenyl borate provides an anti-oxidative effect and mediates cardioprotection during ischemia reperfusion in mice. PLoS One 2017;12:e0189948.
- 25. Suo T, Chen GZ, Huang Y, Zhao KC, Wang T, Hu K. miRNA- 1246 suppresses acute lung injury-induced inflammation and apoptosis via the NF-kB and Wnt/β-catenin signal pathways. Biomed Pharmacother 2018;108:783-91.