Effect of Injectable Ketamine on Histopathological Changes in the Liver in Neonates Born to Pregnant Rats Subjected to Short-Term and Long-Term Anesthesia
|
Afagh Zamen Ghadirli1 , Hessamedin Babaei1 , Marzieh Goodarzi1 , Soheil Shahramirad1 , Aref Arminfar1 , Alireza Avazzadeh1 , Behrooz Yahyaei *2 , Leila Khojasteh3  |
1- Medical Student, Student Research Committee, Shahrood Branch, Islamic Azad University, Shahrood, Iran. 2- Assistant Professor, Department of Medical Sciences, Shahrood Branch, Islamic Azad University, Shahrood, Iran. Assistant Professor, Biological Nanoparticles in Medicine Research Center, Shahrood Branch, Islamic Azad University, Shahrood, Iran. , behroozyahyaei@iau.ac.ir 3- Assistant Professor, Biological Nanoparticles in Medicine Research Center, Shahrood Branch, Islamic Azad University, Shahrood, Iran. |
|
Abstract: (785 Views) |
Background and Objective: Ketamine, a derivative of phencyclidine, is utilized as an anesthetic agent in surgical procedures. Like other medications, it can be associated with various adverse effects on different organs in the body. This study was conducted to determine the effect of injectable ketamine on the histopathological changes in the liver in neonates born to pregnant rats subjected to short-term and long-term anesthesia.
Methods: In this experimental study, 15 pregnant female Wistar rats were randomly divided into 3 groups of 5 each: A control group, a short-term anesthesia group (receiving an intraperitoneal injection of ketamine at a dosage of 25 mg/kg/bw), three times per week for 4 weeks), and a long-term anesthesia group (receiving an intraperitoneal injection of ketamine at a dosage of 75 mg/kg/bw, once per week for 4 weeks). Following parturition and during the lactation period, when the neonatal rats reached two weeks of age, they were initially anesthetized and sacrificed for tissue sampling via intraperitoneal injection of 7 units of ketamine and 3 units of xylazine. Tissue samples, with a thickness of 5 to 6 microns, were sectioned and examined using light microscope after fixation in formalin.
Results: In the short-term anesthesia group, dilation of the centrilobular veins and fluid accumulation were observed, with an intensity score of 2. Additionally, some hepatocytes exhibited degenerative-necrotic changes, characterized by acidophilic and dark cytoplasm, with an intensity score of 1. In the long-term anesthesia group, the liver tissue showed hyperemic changes in the portal space with a score of 1, as well as increased dilation of sinusoidal spaces and centrilobular veins of varying sizes and irregularities, also with an intensity score of 1. Fluid and blood accumulation were also noted in some of these structures. In the control group, cellular structures were maintained with complete regularity, and the intensity score of changes was determined to be zero.
Conclusion: Ketamine administration to pregnant rats can induce histopathological changes in the liver tissue of their offspring. These detrimental changes were more pronounced in the long-term group compared to both the short-term and control group.
|
|
Keywords: Ketamine [MeSH], Anesthesia [MeSH], Histology [MeSH], Pathology [MeSH], Liver [MeSH], Rats [MeSH] Article ID: Vol27-01 |
|
Full-Text [PDF 1056 kb]
(454 Downloads)
| | Abstract (HTML) (10 Views)
|
Type of Study: Original Articles |
Subject:
Physiology - Pharmacology
|
|
|
|
|
References |
1. Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front Hum Neurosci. 2016 Nov;10:612. doi: 10.3389/fnhum.2016.00612. [ DOI] [ PubMed] 2. Wiryana M, Sinardja IK, Budiarta IG, Senapathi TGA, Widnyana M, Aryabiantara IW, et al. Low dose ketamin. Bali J Anesthesiol. 2017;1(1):13-19. doi: 10.15562/bjoa.v1i1.4. [ Link] [ DOI] 3. Radvansky BM, Shah K, Parikh A, Sifonios AN, Le V, Eloy JD. Role of ketamine in acute postoperative pain management: a narrative review. Biomed Res Int. 2015;2015:749837. doi: 10.1155/2015/749837. [ DOI] [ PubMed] 4. Kokane SS, Lin Q. Impact of Early Life Ketamine Exposure on the Developing Brain and Cognitive Sequelae: A Discussion of Apoptotic Neurodegeneration Mechanisms. In: Preedy VR. Neuropathology of Drug Addictions and Substance Misuse. Academic Press. 2016; pp: 581-92. doi: 10.1016/B978-0-12-800212-4.00054-6. [ Link] [ DOI] 5. Li X, Guo C, Li Y, Li L, Wang Y, Zhang Y, et al. Ketamine administered pregnant rats impair learning and memory in offspring via the CREB pathway. Oncotarget. 2017 May;8(20):32433-49. doi: 10.18632/oncotarget.15405. [ DOI] [ PubMed] 6. Yu Y, Quan J, Zou M, Zhao W, Su Y, Xu Y. Effects of ketamine-induced H3K9 hypoacetylation during pregnancy on cardiogenesis of mouse offspring. Birth Defects Res. 2023 Apr;115(7):770-81. doi: 10.1002/bdr2.2168. [ DOI] [ PubMed] 7. Dong C, Anand KJ. Developmental neurotoxicity of ketamine in pediatric clinical use. Toxicol Lett. 2013 Jun 20;220(1):53-60. doi: 10.1016/j.toxlet.2013.03.030. [ DOI] [ PubMed] 8. Erol DD, Aytac I. Current anesthesia for Cesarean Section. Clin J Obstet Gynecol. 2018; 1: 061-066. doi: 10.29328/journal.cjog.1001011. [ Link] [ DOI] 9. Kalsi SS, Wood DM, Dargan PI. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerg Health Threats J. 2011 Apr;4:7107. doi: 10.3402/ehtj.v4i0.7107. [ DOI] [ PubMed] 10. Kalkan Y, Tomak Y, Altuner D, Tumkaya L, Bostan H, Yilmaz A, et al. Hepatic effects of ketamine administration for 2 weeks in rats. Hum Exp Toxicol. 2014 Jan;33(1):32-40. doi: 10.1177/0960327112472990. [ DOI] [ PubMed] 11. Wahdan RAM, Ahmed SMA, Ali MS, Ibrahim MM, Mohamed HE. Abstract PR421: The Acute Effect of Ketamine On the Liver of Adult Male Albino Rats. Anesth Analg. 2016 Sep;123(3S):533-34. doi: 10.1213/01.ane.0000492808.31200.91. [ Link] [ DOI] 12. Venâncio C, Antunes L, Félix L, Rodrigues P, Summavielle T, Peixoto F. Chronic ketamine administration impairs mitochondrial complex I in the rat liver. Life Sci. 2013 Oct;93(12-14):464-70. doi: 10.1016/j.lfs.2013.08.001. [ DOI] [ PubMed] 13. Wong GL, Tam YH, Ng CF, Chan AW, Choi PC, Chu WC, et al. Liver injury is common among chronic abusers of ketamine. Clin Gastroenterol Hepatol. 2014 Oct;12(10):1759-62.e1. doi: 10.1016/j.cgh.2014.01.041. [ DOI] [ PubMed] 14. Wai MS, Chan WM, Zhang AQ, Wu Y, Yew DT. Long-term ketamine and ketamine plus alcohol treatments produced damages in liver and kidney. Hum Exp Toxicol. 2012 Sep;31(9):877-86. doi: 10.1177/0960327112436404. [ DOI] [ PubMed] 15. Cheung HM, Chow TCH, Yew DTW. How Ketamine Affects Livers of Pregnant Mice and Developing Mice? Int J Mol Sci. 2017 May;18(5):1098. doi: 10.3390/ijms18051098. [ DOI] [ PubMed] 16. Hashemnia M, Javedani M, Nikoosafat Z, Abdoli Jamoor S. [Study of Hematological, Biochemical and Histopathological Changes Due to Long-Term Administration of Ketamine in Rat]. JRUMS. 2018;17(7):639-56. [Article in Persian] [ Link] 17. Shin J. Anesthetic Management of the Pregnant Patient: Part 2. Anesth Prog. 2021 Jun;68(2):119-27. doi: 10.2344/anpr-68-02-12. [ DOI] [ PubMed] 18. Mendes PF, Simon KA, Hueza IM. Toxic and immunotoxic evaluation of ketamine and/or ethanol in rats during 28 days. Int J Pharm Pharm Sci. 2017;9(9):205-14. doi: 10.22159/ijpps.2017v9i9.20582. [ Link] [ DOI] 19. Kartal S, Kip G, Küçük A, Aşçı SS, Erdem Ö, Arslan M, et al. The Effects of Dexmedetomidine and Ketamine on Oxidative Injuries and Histological Changes Following Blunt Chest Trauma. Drug Des Devel Ther. 2020 Jul;14:2937-43. doi: 10.2147/DDDT.S258921. [ DOI] [ PubMed] 20. Finbarrs-Bello E, Ojo OP. Effect of Subanaesthetic Dose of Ketamine on Lungs Histology of Wistar Rat. IJRSB. 2018,6(6):1-4. doi: 10.20431/2349-0365.0606001. [ Link] [ DOI] 21. Suckow MA, Stevens KA, Wilson RP. The laboratory rabbit, guinea pig, hamster, and other rodents. 1st ed. New York: Academic Press. 2012; pp: 593-611. 22. Yahyaei B, Babaei H, Khojasteh L, Arminfar A, Jorjani A, Jannati Toupkanloo K, et al. [Histopathological Study of the Kidney Tissue of Neonatal Rats Born From Mothers Receiving Short-term and Long-term Ketamine Injections]. JGUMS. 2024;32(4):308-17. doi: 10.32598/JGUMS.32.4.2089.1. [ Link] [ DOI] 23. Veteläinen RL, Bennink RJ, de Bruin K, van Vliet A, van Gulik TM. Hepatobiliary function assessed by 99mTc-mebrofenin cholescintigraphy in the evaluation of severity of steatosis in a rat model. Eur J Nucl Med Mol Imaging. 2006 Oct;33(10):1107-14. doi: 10.1007/s00259-006-0125-3. [ DOI] [ PubMed] 24. Abdel-Salam OM, Youness ER, Mohammed NA, Abd-Elmoniem M, Omara E, Sleem AA. Neuroprotective and hepatoprotective effects of micronized purified flavonoid fraction (Daflon®) in lipopolysaccharide-treated rats. Drug Discov Ther. 2012 Dec;6(6):306-14. [ PubMed]
|
|
Send email to the article author |
|
|
|