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Effects of Lornoxicam and Intravenous Ibuprofen on Erythrocyte Deformability and Hepatic and Renal Blood Flow in Rats

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Effects of Lornoxicam and Intravenous Ibuprofen on Erythrocyte Deformability and Hepatic and Renal Blood Flow in Rats Journal name: Drug Design, Development and Therapy Article Designation: Original Research Year: 2016 Volume: 10 Drug Design, Development and Therapy Dovepress Running head verso: Arpacı et al Running head recto: Effect of lornoxicam/ibuprofen on RBC deformability and blood flow open access to scientific and medical research DOI: http://dx.doi.org/10.2147/DDDT.S113806 Open Access Full Text Article ORIGINAL RESEARCH Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats Hande Arpacı1,* Background: Change in blood supply is held responsible for anesthesia-related abnormal Faruk Metin Çomu2 tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may Ayşegül Küçük3 be detected after surgery performed under general anesthesia. It was shown that nonsteroidal Bahadır Kösem4 anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) Seyfi Kartal4 ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this Volkan Şıvgın5 study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Hüseyin Cihad Turgut6,* Methods: Eighteen male Wistar albino rats were randomly divided into three groups as follows: Muhammed Enes Aydın5 iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group 5 Derya Sebile Koç (Group C). Drug administration was carried out by the iv route in all groups except Group C. 5 Mustafa Arslan Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed 1Department of Oral and Maxillofacial via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant- Surgery, Faculty of Dentistry, Ankara flow filtrometry system. University, Ankara, 2Department of Medical Physiology, Faculty of Results: Lornoxicam and ibuprofen increased the relative resistance, which is an indicator Medicine, Kırıkkale University, of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Kırıkkale, 3Department of Medical Group I revealed no statistically significant differences P( =0.694), although the erythrocyte Physiology, Faculty of Medicine, University of Dumlupınar, Kütahya, deformability levels in Group L and Group I were statistically higher than the results observed 4Department of Anesthesiology in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were signifi- and Reanimation, Turgut Özal University Hospital, 5Department cantly lower than the same in Group C. of Anesthesiology and Reanimation, Conclusion: We believe that lornoxicam and ibuprofen may lead to functional disorders related Faculty of Medicine, Gazi University, to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte 6Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Gazi deformability. Further studies regarding these issues are thought to be essential. University, Ankara, Turkey Keywords: rat, lornoxicam, iv ibuprofen, erythrocyte deformability, blood flow *These authors contributed equally to this work Introduction Erythrocytes are crucial for normal blood flow and hemodynamics. Cell deform- ability, aggregability, and adherence to endothelial cells are important properties of erythrocytes, which considerably affect blood flow. Under normal flow conditions with a shear stress between normal ranges, erythrocytes are dispersed and properly deformable to maintain tissue perfusion.1 Correspondence: Mustafa Arslan However, abnormal erythrocyte properties are usually seen in various clinical Department of Anesthesiology and situations, such as heart diseases, hypertension, diabetes, cancers, malaria, anemia, Reanimation, Faculty of Medicine, Gazi University, Beşevler, 06510, sickle cell disease, and thrombosis.2 Alterations in hemoglobin structure (inflamma- Ankara, Turkey tion, oxidative stress, and hemoglobinopathies), changes in plasma contents including Tel +90 312 202 6739 Email [email protected] albumin, fibrinogen, and other coagulation elements, as well as pathological states submit your manuscript | www.dovepress.com Drug Design, Development and Therapy 2016:10 2477–2481 2477 Dovepress © 2016 Arpacı et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you http://dx.doi.org/10.2147/DDDT.S113806 hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). Arpacı et al Dovepress associated with diminished flow (ischemia, trauma, and Two hours after administration of lornoxicam and surgery) are suspected underlying factors that may result in iv ibuprofen, the rats were weighed, anesthetized with circulation deterioration.3 ketamine (Ketalar® 50 mg/mL; Pfizer, İstanbul, Turkey), Nonsteroidal anti-inflammatory drugs (NSAIDs) are and euthanasia was performed via intra-abdominal blood frequently used agents for postoperative pain, solely or in uptake. Heparinized total blood samples were used to prepare combination with other types of analgesics. NSAIDs exert erythrocyte packs. Deformability measurements were con- their analgesic effects via inhibition of cyclooxygenase ducted using erythrocyte suspensions with 5% hematocrit in (COX) (prostaglandin synthase G2/H2) enzymes, which phosphate-buffered saline buffer. produce important prostaglandins (PGs) (eg, PGE1, PGE2, PGF2, and PGI2).4 However, especially in the kidney, PGs Hepatic and renal blood flow are prominent elements in regulating important processes measurement related with blood pressure, such as salt/water balance, Hepatic and renal blood flows were recorded. Blood flow renin release, and vascular tone. Following the inhibi- measurements were conducted using a laser Doppler micro- tion of PG synthesis by NSAIDs, salt retention, increased vascular perfusion monitor (OxyLab LDF; Oxford Optronix vascular tone in glomerular vascular bed, and decreased Limited, Oxford, UK) by fixing the probe on the tissue. glomerular filtration rate may occur, and all these effects Deformability measurements may accelerate renal failure, hypertensive disease, and Erythrocyte deformability was measured using a constant-flow end organ damage.5 Effects of NSAIDs on hepatic blood filtrometry system (MP 30, Biopac Systems Inc, Commat, flow have not been widely investigated; however, it is well USA). Erythrocyte suspension, delivered at 1 mL/min flow known that several PGs, such as PGE1 and PGE2, improve rate, was passed through a Nuclepor™ polycarbonate filter hepatic blood flow.6,7 (Thermo Fisher Scientific, Waltham, MA, USA) of 5 µm In this study, we investigated the effects of two diameter, and alterations in the filtration pressure correspond- NSAIDs – lornoxicam and intravenous (iv) ibuprofen – on ing to different flow rates were measured. The alterations in renal and hepatic blood flow, as well as on erythrocyte the pressure were transferred to a computer with an MP30 deformability, in rats. data acquisition system (Biopac Systems, Santa. Barbara, CA, USA). The ratio of the values for the filtration pressure Methods of the cellular suspension and the buffer was calculated, and This study was conducted in the GUDAM Laboratory of Gazi the relative resistance was thereafter calculated. University with the consent of the Experimental Animals Ethics Committee of Gazi University. All of the procedures Statistical analysis were performed according to the accepted standards of the Statistical Package for the Social Sciences (SPSS Inc, Guide for the Care and Use of Laboratory Animals. Chicago, IL, USA) version 12.0 was used for statistical In the study, 18 male Wistar albino rats, weighing analysis. Erythrocyte deformability, as well as the hepatic 225–280 g and raised under the same environmental condi- and renal blood flows, in the study groups was assessed using tions, were used. The rats were maintained under a tem- the Kruskal–Wallis test. Bonferroni-adjusted Mann–Whitney perature of 20°C–21°C with cycles of 12-hour daylight and U-test was used after significant Kruskal–Wallis results to 12-hour darkness; they had free access to food until 2 hours determine which group differs from the others. Results were before the anesthesia procedure. expressed as mean ± standard deviation. Statistical signifi- Three groups of rats constituted the study and control cance was set at a P-value ,0.05 for all analyses and P,0.033 groups. Six randomized rats were grouped as the control; (0.1/3) for Bonferroni-adjusted Mann–Whitney U-test. no surgical procedure was performed on the animals in the control group and they received an equal volume of normal Results saline only (Group C, n=6). In the lornoxicam group, rats Lornoxicam and ibuprofen increased the relative resistance, were administered lornoxicam (Xefo®; Abdi İbrahim İlaç which is an indicator of the erythrocyte deformability, of rats Sanayi ve Tic A.Ş, İstanbul, Turkey) 2 mg/kg intravenously (P=0.016). Comparison
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