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      Repeated Doses of Ketamine Affect the Infant Rat Urogenital System

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          Abstract

          Aim

          Long-term ketamine use is known to create an interstitial cystitis-like problem in the bladder. It is known that long-term intermittent ketamine is applied to the children receiving radiotherapy for sedation. This study was planned to investigate whether this effect seen in the bladder causes similar changes in the kidneys, testicles, epididymis and ductus deferens.

          Materials and Methods

          A total of 12 male Wistar Albino rats for 3 weeks were used in the study. Rats were divided equally into 2 groups as, ketamine and saline. 50 mg/kg ketamine was administered intraperitoneally during 21 days to ketamine (K) groups. 1mL/kg saline was administered intraperitoneally during 21 days to saline (S) groups. At the end of 21 days kidney and testicular tissues were taken for biochemical and histopathological evaluations.

          Results

          Histological assessment of kidney tissue showed that tubule epithelial congestion increased significantly in the ketamine group. Epididymis congestion and distortion in the epididymal gland were found to be different in the ketamine group when testicular tissue was examined. Thiobarbituric acid reactive substances (TBARS) level in testicular and kidney tissue was found to be significantly higher in the ketamine group according to the saline group. Catalase (CAT) enzyme activity was significantly lower in the ketamine group compared to the saline group in both tissues. Paraoxonase-1 (PON-1) enzyme activity was significantly higher in the ketamine group compared to the saline group.

          Conclusion

          We think that the results we have achieved in this study will provide guidance on ketamine, which is repeated in daily anesthesia applications, especially in radiation oncology. But these findings should be supported by clinical and experimental studies that will be conducted in a more detailed and broad series.

          Most cited references37

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          First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid

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            Comparative aspects of the brain growth spurt

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              Ketamine anesthesia during the first week of life can cause long-lasting cognitive deficits in rhesus monkeys.

              Previously our laboratory has shown that ketamine exposure (24h of clinically relevant anesthesia) causes significant increases in neuronal cell death in perinatal rhesus monkeys. Sensitivity to this ketamine-induced neurotoxicity was observed on gestational days 120-123 (in utero exposure via maternal anesthesia) and on postnatal days (PNDs) 5-6, but not on PNDs 35-37. In the present study, six monkeys were exposed on PND 5 or 6 to intravenous ketamine anesthesia to maintain a light surgical plane for 24h and six control animals were unexposed. At 7 months of age all animals were weaned and began training to perform a series of cognitive function tasks as part of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB). The OTB tasks used here included those for assessing aspects of learning, motivation, color discrimination, and short-term memory. Subjects responded for banana-flavored food pellets by pressing response levers and press-plates during daily (M-F) test sessions (50 min) and were assigned training scores based upon their individual performance. As reported earlier (Paule et al., 2009) beginning around 10 months of age, control animals significantly outperformed (had higher training scores than) ketamine-exposed animals for approximately the next 10 months. For animals now over 3 and one-half years of age, the cognitive impairments continue to manifest in the ketamine-exposed group as poorer performance in the OTB learning and color and position discrimination tasks, as deficits in accuracy of task performance, but also in response speed. There are also apparent differences in the motivation of these animals which may be impacting OTB performance. These observations demonstrate that a single 24-h episode of ketamine anesthesia, occurring during a sensitive period of brain development, results in very long-lasting deficits in brain function in primates and provide proof-of-concept that general anesthesia during critical periods of brain development can result in subsequent functional deficits. Supported by NICHD, CDER/FDA and NCTR/FDA. Published by Elsevier Inc.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                dddt
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                11 March 2021
                2021
                : 15
                : 1157-1165
                Affiliations
                [1 ]Department of Anaesthesiology and Reanimation, Ankara City Hospital , Ankara, Turkey
                [2 ]Medical Faculty, Department of Pathology, Yıldırım Bayazit University , Ankara, Turkey
                [3 ]Medical Faculty, Department of Anaesthesiology and Reanimation, Gazi University , Ankara, Turkey
                [4 ]Medical Faculty, Department of Physiology, Kutahya Health Sciences University , Kutahya, Turkey
                [5 ]Medical Faculty, Department of Anaesthesiology and Reanimation, Yıldırım Bayazit University , Ankara, Turkey
                [6 ]Medical Faculty, Department of Biochemistry, Gazi University , Ankara, Turkey
                Author notes
                Correspondence: Mustafa Arslan Medical Faculty, Department of Anesthesiology and Reanimation, Gazi University , Ankara, 06510, TurkeyTel +90 312 202 6739 Email mustarslan@gmail.com
                Author information
                http://orcid.org/0000-0003-4882-5063
                http://orcid.org/0000-0001-9316-9574
                http://orcid.org/0000-0001-9755-033X
                Article
                285862
                10.2147/DDDT.S285862
                7959201
                0bed2a6b-d7e5-4b67-ae90-67ded5eccf99
                © 2021 Kasıkara 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 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).

                History
                : 08 October 2020
                : 23 February 2021
                Page count
                Figures: 5, Tables: 12, References: 37, Pages: 9
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                ketamine,infant rat,testicular tissue,kidney,epididymis
                Pharmacology & Pharmaceutical medicine
                ketamine, infant rat, testicular tissue, kidney, epididymis

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