Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model
Comparison between iloprost and alprostadil for protection against ischemia/reperfusion injury in a rat model
Background/aim: Alprostadil and iloprost are successful agents used for both pulmonary hypertension and extremity ischemiatreatment. Different systemic effects of these agents may change the preferences of clinical usage. Superiority of preventing ischemia/reperfusion (IR) injury is a criterion for clinical preference of these agents. The present study was designed to compare the protectiveeffects of alprostadil and iloprost in a rat model of IR injury.Materials and methods: Twenty-three male Sprague Dawley rats were used (aged 8-12 weeks, mean weight 230 ± 30 g). They wererandomized into 4 groups: Group 1 (iloprost + IR), Group 2 (alprostadil + IR), Group 3 (saline + IR), and Group 4 (control). Undergeneral anesthesia, in all groups except Group 4, the abdominal region was explored and the abdominal aorta was temporarilyclamped for 60 min. After the clamp was removed, 120 min of reperfusion was applied. In Group 4, the rats were placed under generalanesthesia and abdominal exploration was performed without the IR procedure. For all rats, body temperature was kept at 36 °C witha heater pad through the whole procedure. The rats were euthanized under general anesthesia to remove the kidneys and lungs forstudy. Histopathological and biochemical analyses were conducted with kidney and lung tissues. Histopathological scoring was doneby analyzing cellular damage at tissue level. Malondialdehyde (MDA), superoxide dismutase, and glutathione levels were studied forbiochemical analysis.Results: Histopathologic analysis showed that, as compared with alprostadil, iloprost provided a significantly higher level of renalprotection against IR injury (P < 0.01). Renal tissue levels of MDA were significantly lower in the alprostadil group as compared toGroup 3 (P < 0.05).Conclusion: Alprostadil and iloprost seem to provide protection against IR injury, with iloprost being more protective in renal tissue.Alprostadil is more effective than iloprost in protecting lung tissue against IR injury.
___
- Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Cell biology of
ischemia/reperfusion injury. Int Rev Cell Mol Biol 2012; 298:
229-317.
- Liu J, Wang H, Li J. Inflammation and inflammatory cells in
myocardial infarction and reperfusion injury: a double-edged
sword. Clin Med Insights Cardiol 2016; 10: 79-84.
- Qin L, Li G, Kirkiles-Smith N, Clark P, Fang C, Wang Y, Yu ZX,
Devore D, Tellides G, Pober JS et al. Complement C5 inhibition
reduces T cell-mediated allograft vasculopathy caused by both
alloantibody and ischemia reperfusion injury in humanized
mice. Am J Transplant 2016; 16: 2865-2876.
- Ricciotti E, FitzGerald GA. Prostaglandins and inflammation.
Arterioscler Thromb Vasc Biol 2011; 31: 986-1000.
- Çevirme D, Aksoy E, Gül YG, Erdem H, Adademir T, Köksal C,
Bozkurt K. Intravenous iloprost for treatment of critical limb
ischemia in patients unsuitable for revascularization. Vascular
2015; 23: 483-489.
- Caliskan A, Yavuz C, Karahan O, Yazici S, Guclu O, Demirtas S,
Demirtas S, Mavitas B. Iloprost reduces myocardial edema in a
rat model of myocardial ischemia reperfusion. Perfusion 2014;
29: 260-264.
- Çomu FM, Kılıç Y, Özer A, Kirişçi M, Dursun AD, Tatar T, Zor
MH, Kartal H, Küçük A, Boyunağa H et al. Effect of picroside
II on erythrocyte deformability and lipid peroxidation in rats
subjected to hind limb ischemia reperfusion injury. Drug Des
Devel Ther 2016; 10: 927-931.
- Ebrahimi A, Salimi F, Safaei M, Melali H, Jazi AH, Nematbakhsh
M, Mokhtari N, Rasooli H. How effective are alprostadil and
hydrocortisone on reperfusion injury in kidney after distant
organ ischemia? J Res Med Sci 2013; 18: 755-758.
- National Research Council Institute for Laboratory Animal
Research. Guide for the Care and Use of Laboratory Animals.
8th ed. Washington, DC, USA: National Academies Press;
2011.
- Tiryakioglu O, Erkoc K, Tunerir B, Uysal O, Altin HF, Gunes
T, Aydin S. The effect of iloprost and N-acetylcysteine on
skeletal muscle injury in an acute aortic ischemia-reperfusion
model: an experimental study. Biomed Res Int 2015; 2015:
453748.
- Arslan M, Donmez T, Erer D, Tatar T, Comu FM, Alkan M.
Effect of iloprost on erythrocyte deformability in rat’s lower
extremity undergoing an ischemia reperfusion injury Bratisl
Lek Listy 2013; 114: 189-191.
- Ozturk H, Cetinkaya A, Duzcu SE, Tekce BK, Ozturk H.
Carvacrol attenuates histopathogic and functional impairments
induced by bilateral renal ischemia/reperfusion in rats. Biomed
Pharmacother 2018; 98: 656-661.
- Sener G, Toklu H, Ercan F, Erkanli G. Protective effect of betaglucan
against oxidative organ injury in a rat model of sepsis.
Int Immunopharmacol 2005; 5: 1387-1396.
- Akkaya H, Kilic E, Dinc SE, Yilmaz B. Postacute effects of
kisspeptin-10 on neuronal injury induced by L-methionine in
rats. J Biochem Mol Toxicol 2014; 28: 373-377.
- Placer ZA, Cushman LL, Johnson BC. Estimation of product of
lipid peroxidation (malonyl dialdehyde) in biological systems.
Anal Biochem 1966; 16: 359-364.
- Sun Y, Oberley LW, Li Y. A simple method for clinical assay of
superoxide dismutase. Clin Chem 1988; 34: 497-500.
- Ellman GL, Courtney KD, Andres V Jr, Feather-Stone
RM. A new and rapid colorimetric determination of
acetylcholinesterase activity. Biochem Pharmacol 1961; 7: 88-
95.
- Yassin MM, Harkin DW, Barros D’Sa AA, Halliday
MI, Rowlands BJ. Lower limb ischemia reperfusion injury
triggers a systemic inflammatory response and multiple organ
dysfunction. World J Surg 2002; 26: 115-121.
- Birukova AA, Wu T, Tian Y, Meliton A, Sarich N, Tian X, Leff
A, Birukov KG. Iloprost improves endothelial barrier function
in lipopolysaccharide-induced lung injury. Eur Respir J 2013;
41: 165-176.
- Saji T, Myoishi M, Sugimura K, Tahara N, Takeda
Y, Fukuda K, Olschewski H, Matsuda Y, Nikkho S, Satoh T.
Efficacy and safety of inhaled iloprost in Japanese patients
with pulmonary arterial hypertension - Insights from the
IBUKI and AIR studies. Circ J 2016; 80: 835-842.
- 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 ischemia-reperfusion injury during
abdominal aortic aneurysm surgery. Surg Today 2006; 36: 140-
146.
- Dong MF, Ma ZS, Ma SJ, Chai SD, Tang PZ, Yao DK, Wang L.
Effect of prostaglandin E1 on pulmonary arterial hypertension
following corrective surgery for congenital heart disease. J
Cardiovasc Pharmacol Ther 2012; 17: 303-307.
- Zhang S, Duehrkop C, Plock JA, Rieben R. Inhalation
anesthesia of rats: influence of the fraction of inspired oxygen
on limb ischemia/reperfusion injury. Lab Anim 2016; 50: 185-
197.
- Adaikan PG, Tai NY, Lau LC, Karim SM, Kottegoda SR. A
comparison of some pharmacological actions of prostaglandin
E1, 6-oxo-PGE1 and PGI2. Prostaglandins 1984; 27: 505-516.
- Hsieh CC, Hsieh SC, Chiu JH, Wu YL. Protective effects of
N-acetylcysteine and a prostaglandin E1 analog, alprostadil,
against hepatic ischemia: reperfusion injury in rats. J Tradit
Complement Med 2014; 4: 64-71.
- Spargias K, Adreanides E, Demerouti E, Gkouziouta A,
Manginas A, Pavlides G, Voudris V, Cokkinos DV. Iloprost
prevents contrast-induced nephropathy in patients with renal
dysfunction undergoing coronary angiography or intervention.
Circulation 2009; 120: 1793-1799.
- Turker RK, Demirel E, Ercan ZS. Iloprost preserves kidney
function against anoxia. Prostaglandins Leukot Essent Fatty
Acids 1988; 31: 45-52.
- McCullough PA, Tumlin JA. Prostaglandin-based renal
protection against contrast-induced acute kidney injury.
Circulation 2009; 120: 1749-1751.
- Halliwell B, Gutteridge JM. The importance of free radicals and
catalytic metal ions in human diseases. Mol Aspects Med 1985;
8: 89-193.
- Li FJ, Hsu T, Li HX, Shi JZ, Du ML, Wang XY, Zhang
WT. Protective effect and mechanism of lithium chloride
pretreatment on myocardial ischemia-reperfusion injury in
rats. Asian Pac J Trop Med 2014; 7: 744-748.
- Chiang CH, Hsu K, Yan HC, Harn HJ, Chang DM.
PGE1, dexamethasone, U-74389G, or Bt2-cAMP as
an additive to promote protection by UW solution in I/R injury.
J Appl Physiol 1997; 83: 583-590.