Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats
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ORIGINAL ARTICLE
Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats Mehmet Selim Çömez 1 & Mustafa Cellat 2 & Hüseyin Özkan 3 & Yakup Borazan 4 & Tuba Aydın 5 & İshak Gökçek 2 & Erdinç Türk 6 & Mehmet Güvenç 2 & Ahmet Çakır 7 & Şule Yurdagül Özsoy 8 Received: 21 November 2019 / Accepted: 8 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The antioxidant and cardioprotective effects of oleuropein have been reported in several studies; however, its effect on ketamine cardiotoxicity has not been known yet. The aim of this study was to investigate the effects of oleuropein in ketamine-induced cardiotoxicity model in rats. A total of 28 male Wistar Albino rats were included in the study and they were randomly divided into four groups, each having seven rats. Group 1 (control): rats were given 1 mL of DMSO by oral gavage method for 7 days. Group 2 (ketamine): on the seventh day of the study, 60 mg/kg ketamine was administered intraperitoneally. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Group 3 (oleuropein): rats were given 200 mg/kg/day oleuropein by oral gavage method for 7 days. Group 4 (oleuropein + ketamine): rats were given 1 × 200 mg/kg oleuropein by oral gavage method for 7 days. Furthermore, 60 mg/kg ketamine was administered intraperitoneally on the seventh day of the experiment. Then, 60 mg/kg ketamine was administered intraperitoneally every 10 min for 3 h. Serum cardiac marker (TnI, CK-MB and CK) levels were measured. Histopathological analysis was performed on a portion of the cardiac tissue. Cardiac tissue oxidative stress and antioxidant markers (MDA, GSH, GSH.Px and CAT), TNF-α, IL-6, NF-κB, COX-2 and Nrf-2 gene expressions, and protein conversion levels of related genes were determined. Data obtained showed that ketamine administration increased MDA (p < 0.001), TNF-α (p < 0.01), IL-6 (p < 0.01), COX-2 (p < 0.001) and NF-κB (p < 0.001) levels, as well as serum TnI (p < 0.001), CK-MB (p < 0.001) and CK (p < 0.01) levels whereas decreased GSH (p < 0.05) and Nrf-2 (p < 0.05) levels, as well as GSH-Px (p < 0.001) and CAT (p < 0.05) enzyme activities. Oleuropein administration was observed to decrease MDA, TNF-α, IL-6, COX-2, NF-κB, TnI, CK-MB and CK levels close to the control group and to increase GSH levels and GSHPx and CAT enzyme activities close to the control group. This study showed that oleuropein administration reversed the increased oxidative stress and inflammation as a result of the use of ketamine and had protective effects on the heart. Keywords Ketamine . Oleuropein . Cardiotoxicity
Introduction Ketamine, an N-Methyl-D-aspartate (NMDA) antagonist, has been found to produce analgesic effects in the human body. It * Mehmet Selim Çömez [email protected]; [email protected] 1
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Department of Anesthesiology and Reanimation, Faculty of Medicine, Hatay Mustafa Kemal University, 31300 Hatay, Turkey Department of Physiology, Faculty of Veterinary Medicine, Hatay Mustafa Kemal University, Hatay
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