Ukrain (NSC 631570) ameliorates intestinal ischemia-reperfusion-induced acute lung injury by reducing oxidative stress

Cengiz Kocak; Fatma Emel Kocak; Raziye Akcilar; Aydin Akcilar; Bircan Savran; Sezgin Zeren; Zulfu Bayhan; Zeynep Bayat

doi:10.17305/bjbms.2016.875

Authors

Cengiz Kocak Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey http://orcid.org/0000-0003-3819-6822
Fatma Emel Kocak Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey http://orcid.org/0000-0001-5549-3883
Raziye Akcilar Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Aydin Akcilar Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Bircan Savran Department of Pediatric Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Sezgin Zeren Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Zulfu Bayhan Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Zeynep Bayat Department of Biochemistry, Faculty of Art and Science, Dumlupinar University, Kutahya, Turkey

DOI:

https://doi.org/10.17305/bjbms.2016.875

Keywords:

Ischemia-reperfusion injury, lung injury, oxidative stress, ukrain

Abstract

Intestinal ischemia-reperfusion (I/R) causes severe destruction in remote organs. Lung damage is a frequently seen complication after intestinal I/R. Ukrain (NSC 631570) is a synthetic thiophosphate derivative of alkaloids from the extract of the celandine (Chelidonium majus L.) plant. We investigated the effect of Ukrain in animals with lung injury induced by intestinal I/R. Adult male Spraque-Dawley rats were randomly divided into four groups: control, Ukrain, I/R, I/R with Ukrain. Before intestinal I/R was induced, Ukrain was administered intraperitoneally at a dose of 7.0 mg/body weight. After 1 h ischemia and 2 h reperfusion period, lung tissues were excised. Tissue levels of total oxidative status (TOS), total antioxidant status (TAS) were measured and oxidative stress indices (OSI) were calculated. Lung tissues were also examined histopathologically. TOS and OSI levels markedly increased and TAS levels decreased in the I/R group compared to the control group (P < 0.05). TOS and OSI levels markedly decreased and TAS levels increased in the I/R with Ukrain group compared with the group subjected to IR only (P < 0.05). Severe hemorrhage, alveolar septal thickening, and leukocyte infiltration were observed in the I/R group. In the I/R with Ukrain group, morphologic changes occurring as a result of lung damage attenuated and histopathological scores reduced compared to the I/R group (P < 0.05). Our results suggest that Ukrain pretreatment could reduce lung injury induced by intestinal I/R induced via anti-inflammatory and antioxidant effects.

Citations

Downloads

Download data is not yet available.

Author Biographies

Cengiz Kocak, Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of Pathology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Fatma Emel Kocak, Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of Medical Biochemistry, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Raziye Akcilar, Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of Physiology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Aydin Akcilar, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Bircan Savran, Department of Pediatric Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of Pediatric Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Sezgin Zeren, Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Zulfu Bayhan, Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey

Department of General Surgery, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey
Zeynep Bayat, Department of Biochemistry, Faculty of Art and Science, Dumlupinar University, Kutahya, Turkey

Department of Biochemistry, Faculty of Art and Science, Dumlupinar University, Kutahya, Turkey

References

Teke Z, Sacar M, Yenisey C, Atalay AO, Kavak T, Erdem E. Activated protein C attenuates intestinal mucosal injury after mesenteric ischemia/reperfusion. J Surg Res 2008;149:219-30.

http://dx.doi.org/10.1016/j.jss.2007.10.011

Berlanga J, Prats P, Remirez D, Gonzalez R, Lopez-Saura P, Aguiar J, et al. Prophylactic use of epidermal growth factor reduces ischemia/reperfusion intestinal damage. Am J Pathol 2002;161:373-9.

http://dx.doi.org/10.1016/S0002-9440(10)64192-2

Zhao W, Gan X, Su G, Wanling G, Li S, Hei Z, et al. The interaction between oxidative stress and mast cell activation plays a role in acute lung injuries induced by intestinal ischemia-reperfusion. J Surg Res 2014;187:542-52.

http://dx.doi.org/10.1016/j.jss.2013.10.033

Khanna A, Rossman JE, Fung HL, Caty MG. Intestinal and hemodynamic impairment following mesenteric ischemia/reperfusion. J Surg Res 2001;99:114-9.

http://dx.doi.org/10.1006/jsre.2001.6103

Swank GM, Deitch EA. Role of the gut in multiple organ failure: bacterial translocation and permeability changes. World J Surg 1996;20:411-7.

http://dx.doi.org/10.1007/s002689900065

Uglyanitsa KN, Nefyodov LI, Doroshenko YM, Nowicky JW, Volchek IV, Brzosko WJ, Hodysh YJ. Ukrain: a novel antitumor drug. Drugs Exp Clin Res 2000;26:341-56.

Ernst E, Schmidt K. Ukrain - a new cancer cure? A systematic review of randomised clinical trials. BMC Cancer 2005;5:69.

http://dx.doi.org/10.1186/1471-2407-5-69

Jagiello-Wójtowicz E, Kleinrok Z, Urbanska EM. Ukrain (NSC-631570) in experimental and clinical studies: a review. Drugs Exp Clin Res 1998;24:213-9.

Cordes N, Plasswilm L, Bamberg M, Rodemann HP. Ukrain, an alkaloid thiophosphoric acid derivative of Chelidonium majus L. protects human fibroblasts but not human tumour cells in vitro against ionizing radiation. Int J Radiat Biol 2002;78:17-27.

http://dx.doi.org/10.1080/09553000110089991

Akcilar R, Akcilar A, Savran B, Ayada C, Kocak C, Kocak FE, Genc O. Effects of ukrain in rats with intestinal ischemia and reperfusion. J Surg Res 2015;195:67-73.

http://dx.doi.org/10.1016/j.jss.2014.12.040

Institute for Laboratory Animal Research, National Research Council. Guide for the Care and Use of Laboratory Animals. Washington, D.C.: National Academy Press;2010:248.

Wasserberg N, Pileggi A, Salgar SK, Ruiz P, Ricordi C, Inverardi L, et al. Heme oxygenase-1 upregulation protects against intestinal ischemia/reperfusion injury: a laboratory based study. Int J Surg 2007;5:216-24.

http://dx.doi.org/10.1016/j.ijsu.2006.06.001

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976;72:248-54.

http://dx.doi.org/10.1016/0003-2697(76)90527-3

Erel O. A novel automated method to measure total antioxidant response against potent free radical reactions. Clin Biochem 2004;37:112-9.

http://dx.doi.org/10.1016/j.clinbiochem.2003.10.014

Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem 2005;38:1103-11.

http://dx.doi.org/10.1016/j.clinbiochem.2005.08.008

Tufek A, Tokgoz O, Aliosmanoglu I, Alabalik U, Evliyaoglu O, Ciftci T,et al. The protective effects of dexmedetomidine on the liver and remote organs against hepatic ischemia reperfusion injury in rats. Int J Surg 2013;11:96-100.

http://dx.doi.org/10.1016/j.ijsu.2012.12.003

Yamanel L, Kaldirim U, Oztas Y, Coskun O, Poyrazoglu Y, Durusu M et al. Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats. Int J Med Sci 2011;8:48-55.

http://dx.doi.org/10.7150/ijms.8.48

Stoney RJ, Cunninghan CG. Acute mesenteric ischemia. Surgery 1993;114:489-90.

Cerqueira NF, Hussni CA, Yoshida WB. Pathophysiology of mesenteric ischemia/reperfusion: a review. Acta Cir Bras 2005;20:336-43.

http://dx.doi.org/10.1590/S0102-86502005000400013

Shen L, Zhang J. Ginsenoside Rg1 increases ischemia-induced cell proliferation and survival in the dentate gyrus of adult gerbils. Neurosci Lett 2003;344:1-4.

http://dx.doi.org/10.1016/S0304-3940(03)00318-5

Teke Z, Sacar M, Yenisey C, Atalay AO, Bicakci T, Erdem E. Activated protein C attenuates intestinal reperfusion-induced acute lung injury: an experimental study in a rat model. Am J Surg 2008;195:861-73.

http://dx.doi.org/10.1016/j.amjsurg.2007.06.025

Boyuk A, Onder A, Kapan M, Gumus M, Firat U, Basaralι MK, et al. Ellagic acid ameliorates lung injury after intestinal ischemia-reperfusion. Pharmacogn Mag 2011;7:224-8.

http://dx.doi.org/10.4103/0973-1296.84236

Luo C, Yuan D, Zhao W, Chen H, Luo G, Su G, et al. Sevoflurane ameliorates intestinal ischemia-reperfusion-induced lung injury by inhibiting the synergistic action between mast cell activation and oxidative stress. Mol Med Rep 2015;12:1082-90.

http://dx.doi.org/10.3892/mmr.2015.3527

Torun E, Gedik AH, Cakir E, Umutoglu T, Gok O, Kilic U. Serum paraoxonase, TAS, TOS and ceruloplasmin in brucellosis. Int J Clin Exp Med 2014;7:1592-97.

Aycicek A, Ipek A. Maternal active or passive smoking causes oxidative stress in cord blood. Eur J Pediatr 2008;167:81–5.

http://dx.doi.org/10.1007/s00431-007-0433-z

Guzel A, Kanter M, Guzel A, Pergel A, Erboga M. Anti-inflammatory and antioxidant effects of infliximab on acute lung injury in a rat model of intestinal ischemia/reperfusion. J Mol Histol 2012;43:361-9.

http://dx.doi.org/10.1007/s10735-012-9396-0

Habermehl D, Kammerer B, Handrick R, Eldh T, Gruber C, Cordes N, et al. Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. BMC Cancer 2006;6:14.

http://dx.doi.org/10.1186/1471-2407-6-14

Nowicky JW, Manolakis G, Meijer D, Vatanasapt V, Brzosko WJ. Ukrain both as an anticancer and immunoregulatory agent. Drugs Exp Clin Res 1992;18 Suppl:51-4.

Hohenwarter O, Strutzenberger K, Katinger H, Liepins A, Nowicky JW. Selective inhibition of in vitro cell growth by the anti-tumour drug Ukrain. Drugs Exp Clin Res 1992;18 Suppl:1-4.

Nowicky JW, Hiesmayr W, Nowicky W, Liepins A. Influence of Ukrain on DNA, RNA and protein synthesis in malignant cells. Drugs Exp Clin Res 1996;22:81-91.

Zhalilo LI, Susak YM, Zemskov SV, Susak IA. Influence of Ukrain on the redox processes of hepatocytes. Drugs Exp Clin Res 1996;22:189-91.

Nefyodov LI, Uglyanitsa KN, Nechiporenko NA, Smirnov VY, Brzosko W, Karavay NL. New biochemical mechanisms of the anticancer effect of Ukrain in the treatment of cancer of the urinary bladder. Drugs Exp Clin Res 2000;26:195-9.

Savran B, Yerlikaya A, Erdogan E, Genc O. Anticancer agent ukrain and bortezomib combination is synergistic in 4T1 breast cancer cells. Anticancer Agents Med Chem 2014;14:466-72.

http://dx.doi.org/10.2174/18715206113139990318

Habermehl D, Kammerer B, Handrick R, Eldh T, Gruber C, Cordes N, et al. Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. BMC Cancer 2006;6:14.

http://dx.doi.org/10.1186/1471-2407-6-14

Chan SL, Lee MC, Tan KO, Yang LK, Lee AS, Flotow H, et al. Identification of chelerythrine as an inhibitor of BclXL function. J Biol Chem 2003;278:20453-6.

http://dx.doi.org/10.1074/jbc.C300138200

Roublevskaia IN, Haake AR, Polevoda BV. Bcl-2 overexpression protects human keratinocyte cells from Ukrain-induced apoptosis but not from G2/M arrest. Drugs Exp Clin Res 2000;26:149-56.

Roublevskaia IN, Polevoda BV, Ludlow JW, Haake AR. Induced G2/M arrest and apoptosis in human epidermoid carcinoma cell lines by semisynthetic drug Ukrain. Anticancer Res 2000;20:3163-7.

Roublevskaia IN, Haake AR, Ludlow JW, Polevoda BV. Induced apoptosis in human prostate cancer cell line LNCaP by Ukrain. Drugs Exp Clin Res 2000;26:141-7.

Skivka LM, Fedorchuk OG, Rudyk MP, Pozur VV, Khranovska NM, Grom MY, et al. Antineoplastic drug NSC631570 modulates functions of hypoxic macrophages. Tsitol Genet 2013;47:70-82.

http://dx.doi.org/10.3103/s0095452713050095

Koriem KM, Arbid MS, Asaad GF. Chelidonium majus leaves methanol extract and its chelidonine alkaloid ingredient reduce cadmium-induced nephrotoxicity in rats. J Nat Med 2013;67:159-67.

http://dx.doi.org/10.1007/s11418-012-0667-6

Park JE, Cuong TD, Hung TM, Lee I, Na M, Kim JC, et al. Alkaloids from Chelidonium majus and their inhibitory effects on LPS-induced NO production in RAW264.7 cells. Bioorg Med Chem Lett 2011;21:6960-3.

http://dx.doi.org/10.1016/j.bmcl.2011.09.128