İbrahim Özkan ALATAŞ, Cengiz OVALI, Orhan ÖZATİK, Mustafa Behçet SEVİN, Betül CAN, Elif GÜNEYSU, Atacan Emre KOÇMAN

The effects of iloprost and alprostadil on ischemia-reperfusion injury in preventing inflammation, tissue degeneration, and apoptosis in rat skeletal muscle

Background/aim: The protective effects of prostaglandin (PG) analogs on ischemia-reperfusion (I/R) have been well documented; however, comparative studies are lacking. The aim of the present study was to determine whether iloprost or alprostadil is more effective in preventing muscle I/R injury. Materials and methods: Thirty-two rats were divided into four groups (n = 8): sham, control, IL (I/R + iloprost), and AL (I/R + alprostadil). I/R was induced by a tourniquet in the hindlimb for 3 h/3 h. The IL and AL groups received iloprost (0.5 ng kg 1 min 1) and alprostadil (0.05 µg kg 1 min 1) during reperfusion, respectively. After 6 h, blood and muscles were collected for analyses. Results: Serum TNF-α and IL-1β levels were decreased in the IL and AL groups compared with the control group (P < 0.05), whereas IL-6 levels did not change significantly. Tissue malondialdehyde levels were significantly lower in the IL and AL groups (P < 0.05). Tissue catalase levels showed no difference. The histological damage scores and apoptosis scores were both significantly decreased in the IL and AL groups compared with the control group (P< 0.05). Conclusion: The present study indicated that iloprost and alprostadil attenuated I/R injury in skeletal muscle. However, no comparable difference was evident regarding the efficacies of either PG analog.

PDF

___

1. Della Bella S, Molteni M, Mocellin C, Fumagalli S, Bonara P, Scorza R. Novel mode of action of iloprost: in vitro down-regulation of endothelial cell adhesion molecules. Prostaglandins Other Lipid Mediat 2001; 65: 73-83.
2. Eltzschig HK, Collard CD. Vascular ischaemia and reperfusion injury. Br Med Bull 2004; 70: 71-86.
3. De Donato G, Gussoni G, Cao P, Setacci C, Pratesi C, Mazzone A, Ferrari M, Veglia F, Bonizzoni E, Settembrini P et al. Acute limb ischemia in elderly patients: can iloprost be useful as an adjuvant to surgery? Results from the ILAILL study. Eur J Vasc Endovasc Surg 2007; 34: 194-198.
4. Mohan C, Marini C, Gennaro M, Ascer E. The value and limitation of iloprost infusion in decreasing skeletal muscle necrosis. J Vasc Surg 1992; 16: 268-273.
5. Ricciotti E, FitzGerald GA. Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 2011; 31: 986-1000.
6. Tauber S, Menger MD, Lehr HA. Microvascular in vivo assessment of reperfusion injury: significance of prostaglandin E1 and I2 in postischemic no-reflow and reflow-paradox. J Surg Res 2004; 120: 1-11.
7. Belkin M, Wright JG, Hobson RW. Iloprost infusion decreases skeletal muscle ischemia-reperfusion injury. J Vasc Surg 1990; 11: 77-83.
8. Blebea J, Cambria RA, DeFouw D, Feinberg RN, Hobson RW, Duran WN. Iloprost attenuates the increased permeability in skeletal muscle after ischemia and reperfusion. J Vasc Surg 1990; 12: 657-666.
9. Mohan C, Ascer E, Marini C, Maughan R, Gennaro M. Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle? J Cardiovasc Surg (Torino) 1991; 33: 613-618.
10. Bozkurt A. Alpha-tocopherol (vitamin E) and iloprost attenuate reperfusion injury in skeletal muscle ischemia/reperfusion injury. J Cardiovasc Surg (Torino) 2002; 43: 693-696.
11. Emrecan B, Tulukoğlu E, Bozok Ş, Aksun M, Yağdı S, Özcan AV, Saçar M, Gürbüz A. Iloprost and pentoxifylline attenuate ischemia-reperfusion injury in skeletal muscle in rabbit model. Ulus Travma Acil Cer 2008; 14: 182-187.
12. Avci T, Erer D, Kucuk A, Oztürk Y, Tosun M, Oktar GL, Arslan M, Iriz E, Kavutcu M, Tatar T. The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model. J Surg Res 2014; 187: 162-168.
13. Hong JP, Chung YK, Chung SH. The effect of prostaglandin E1 versus ischemia-reperfusion injury of musculocutaneous flaps. Ann Plast Surg. 2001; 47: 316-321.
14. Antonio L, Evora P, Piccinato C. Use of alprostadil, a stable prostaglandin E1 analogue, for the attenuation of rat skeletal muscle ischemia and reperfusion injury. Minerva Chir 2009; 64: 559-564.
15. Milcan A, Arslan E, Bagdatoglu OT, Bagdatoglu C, Polat G, Kanik A, Talas DU, Kuyurtar F. The effect of alprostadil on ischemiareperfusion injury of peripheral nerve in rats. Pharmacol Res 2004; 49 : 67-72.
16. Rowlands T, Gough M, Homer-Vanniasinkam S. Do prostaglandins have a salutary role in skeletal muscle ischaemiareperfusion injury? Eur J Vasc Endovasc Surg 1999; 18: 439-444.
17. Erer D, Özer A, Demirtaş H, Gönül İI, Kara H, Arpacı H, Çomu FM, Oktar GL, Arslan M, Küçük A. Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia-reperfusion injury in rats. Drug Des Devel Ther 2016; 10: 2651-2658.
18. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979; 95: 351-358.
19. Beutler E. Red Cell Metabolism: A Manual of Biochemical Methods. 2nd ed. New York, NY, USA: Grune & Stratton; 1975.
20. Arslan M, Donmez T, Erer D, Tatar T, Comu F, Alkan M. Effect of iloprost on erythrocyte deformability in rats lower extremity undergoing an ischemia reperfusion injury. Bratisl Lek Listy 2012; 114: 189-191.
21. Thomson I, Egginton S, Hudlicka O, Sims M. Iloprost reduces leukocyte adhesion in skeletal muscle venules following ischaemia in a rat model of femorodistal bypass. Eur J Vasc Surg 1994; 8: 335-341.
22. Iriz E, Erer D, Kula S, Olgunturk R, Halit V. Use of microsurgery and iloprost in the infantile arterial injuries. Circ J 2007; 71: 554-558.
23. Lin X, Zhang Y, Cui Y, Wang L, Wang J, Tang X. Determination of alprostadil in rat plasma by ultra performance liquid chromatographyelectrospray ionizationtandem mass spectrometry after intravenous administration. J Pharm Biomed Anal 2009; 49: 983-988.
24. Huk I, Brovkovych V, Nanobashvili J, Neumayer C, Polterauer P, Prager M, Patton S, Malinski T. Prostaglandin E1 reduces ischemia/reperfusion injury by normalizing nitric oxide and superoxide release. Shock 2000; 14: 234-242.
25. Abdel-Rahman U, Risteski P, Klaeffling C, Mitrev Z, Ackermann H, Matheis G, Moritz A, Beyersdorf F. The influence of controlled limb reperfusion with PGE1 on reperfusion injury after prolonged ischemia. J Surg Res 2009; 155: 293-300.
26. Fräßdorf J, Luther B, Müllenheim J, Otto F, Preckel B, Schlack W, Thämer V. Influence of groin incision, duration of ischemia, and prostaglandin E1 on ischemia-reperfusion injury of the lower limb. J Cardiothorac Vasc Anesth 2006; 20: 187- 195.
27. Sako H, Hadama T, Miyamoto S, Anai H, Wada T, Iwata E, Hamamoto H, Tanaka H, Urushino K, Shuto T. Effect of prostaglandin E1 on ischemiareperfusion injury during abdominal aortic aneurysm surgery. Surg Today 2006; 36: 140- 146.
28. Valenzuela A. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 1991; 48: 301-309.