Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats

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 GSH-Px 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.

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Funding

This study funded by the Scientific Research Project Coordination of the Hatay Mustafa Kemal University, Turkey (No: 18.M.062/2018).

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Authors

Contributions

MSC and MC designed the study. MSC, MG, IG and MC performed the in vivo study. TA, ET and AC isolated oleuropein. SYO performed the histopathological analysis. MG, IG and HO analysed the data. MSC, YB, MC and HO wrote the manuscript.

Corresponding author

Correspondence to Mehmet Selim Çömez.

Ethics declarations

All procedures were performed in accordance with the directions of the Guide for the Care and Use of Laboratory Animals, and the experimental procedures were approved by the Experimental Animal Ethics Committee of Mustafa Kemal University (MKU-HADYEK 2018/1-5).

Ethical statement

After approval of the Local Ethics Committee for Animal Trials of the Hatay Mustafa Kemal University (HMKU) (No: 2018/1-5), the study conducted at the Experimental Animal Application and Research Center, HMKU, Turkey.

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The authors decalare that they have no conflict of interest.

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Çömez, M.S., Cellat, M., Özkan, H. et al. Protective effect of oleuropein on ketamine-induced cardiotoxicity in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1691–1699 (2020). https://doi.org/10.1007/s00210-020-01870-w

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Keywords

  • Ketamine
  • Oleuropein
  • Cardiotoxicity