Evaluating Vitamin E's Antioxidative Effect on Carbamazepine-Induced Spleen Damage in Rat Models
DOI:
https://doi.org/10.36283/PJMD13-3/018Keywords:
Carbamazepine, Vitamin E, Spleen, oxidative stress, morphology, hematologyAbstract
Background: The spleen is essential for the body’s homeostasis and immune system. Carbamazepine (CBZ) is known to cause toxicity to several organs, including the spleen, through oxidative stress, however, vitamin E (Vit E) is a proven antioxidant against toxins. Thus, this study evaluated the antioxidative effect of Vit E on hematological and splenic toxic changes, caused by carbamazepine in rats.
Methods: This in-vivo preclinical experimental study was conducted from March-June 2020, at Jinnah Medical and Dental College, Karachi. Forty adult male rats, weighing 150-200 grams were included and randomly divided into 4 groups. Group I was control; Group II received oral Carbamazepine (50mg/kg/day), Group III received Carbamazepine (50mg/kg/day) with Vit E (200mg/kg/day), and Group IV received Vit E (200mg/kg/day) daily. After 6 weeks, animals were sacrificed, blood samples were drawn and splenic tissue was processed for morphological examination. SPSS version 22 was used, and ANOVA was applied to investigate the difference of means with p≤0.05 considered significant.
Results: Our findings showed that Group II rats had significantly decreased final body weights, and absolute and relative spleen weights compared to control. Lower hemoglobin, lymphocytes, and platelets, and significantly increased TLC and neutrophils were observed in Group II compared to control and Group IV. Histology showed a thickened capsule, reduced white pulp, and congested red pulp in Group II spleens whereas these toxic effects were reduced in Group III.
Conclusion: Our study demonstrated that the hematologic and splenic toxic effects of carbamazepine were lessened significantly with the antioxidative properties of vitamin E.
Keywords: Carbamazepine, Vitamin E, Spleen, Oxidative Stress, Hematology.
References
Rashad E, Hussein S, Bashir DW, Ahmed ZO, El-Habback H. Anatomical, histological, histochemical, scanning and transmission electron microscopic studies on water Buffalo (Bubalus Bubalis) Spleen. J Crit Rev. 2020;7(17):6154-6173.
Dumas L, Roussel C, Buffet P. Intra-erythrocytic vacuoles in asplenic patients: elusive genesis and original clearance of unique organelles. Front Physiol. 2023;14:1324463. https://doi:10.3389/fphys.2023.1324463
Kashimura M. The human spleen is the center of the blood defense system. Int J Hematol. 2020;112(2):147-158. https://doi.org/10.1007/s12185-020-02912-y
Wang X, Yan X, Yang Y, Yang W, Zhang Y, Wang J, Ye D, Wu Y, Ma P, Yan B. Dibutyl phthalate-mediated oxidative stress induces splenic injury in mice and the attenuating effects of vitamin E and curcumin. Food Chem Toxicol. 2020;136:110955. https://doi.org/10.1016/j.fct.2019.110955
García-Medina S, Galar-Martínez M, Gómez-Oliván LM, del Consuelo Torres-Bezaury RM, Islas-Flores H, Gasca-Pérez E. The relationship between cyto-genotoxic damage and oxidative stress produced by emerging pollutants on a bioindicator organism (Allium cepa): the carbamazepine case. Chemosphere. 2020;253:126675. https://doi.org/10.1016/j.chemosphere.2020.126675
Akorede GJ, Ambali SF, Olatunji AO, Shittu M, Aremu A, Basiru A, et al. Protective effect of vitamin C on chronic carbamazepine-induced reproductive toxicity in male wistar rats. Toxicol Rep. 2020;7:269-276. https://doi.org/10.1016/j.toxrep.2020.01.017
Chen RJ, Ershad M, Dela Cruz M, Mostafa AM. Carbamazepine toxicity masquerading as complex febrile seizures in a pediatric patient. Case Rep Emerg Med. 2020;2020. https://doi.org/10.1155/2020/1790310
Beydoun A, DuPont S, Zhou D, Matta M, Nagire V, Lagae L. Current role of carbamazepine and oxcarbazepine in the management of epilepsy. Seizure. 2020;83:251-263. https://doi.org/10.1016/j.seizure.2020.10.018
Zita L, Kurhan S, Krunt O, Chmelíková E, Kraus A, Čítek J, et al. The Effect of Carbamazepine on Performance, Carcass Value, Hematological and Biochemical Blood Parameters, and Detection of Carbamazepine and Its Metabolites in Tissues, Internal Organs, and Body Fluids in Growing Rabbits. Anim. 2023; 13(12):2041. https://doi.org/10.3390/ani13122041
Blaner WS, Shmarakov IO, Traber MG. Vitamin A and vitamin E: will the real antioxidant please stand up?. Annu Rev Nutr. 2021;41:105-131. https://doi.org/10.1146/annurev-nutr-082018-124228
Mandil R, Prakash A, Rahal A, Singh SP, Sharma D, Kumar R, et al. In vitro and in vivo effects of flubendiamide and copper on cyto-genotoxicity, oxidative stress and spleen histology of rats and its modulation by resveratrol, catechin, curcumin and α-tocopherol. BMC Pharmacol Toxicol. 2020;21:1-7. https://doi.org/10.1186/s40360-020-00405-6
Andrade-Mena CE. Immunodepression induced by carbamazepine administration is mediated by CD 8+ spleen T cells. Int J Tissue React. 1996;18(2-3):81-85.
Pacific R, Di Carlo S, Bacosi A, Pichini S, Zuccaro P. Immunomodulating properties of carbamazepine in mice. Int J Immunopharmacol. 1992;14(4):605-611.https://doi.org/10.1016/0192-0561(92)90121-Z
Osuntokun OS, Babatunde AA, Olayiwola G, Atere TG, Oladokun OO, Adedokun KI. Assessment of the biomarkers of hepatotoxicity following carbamazepine, levetiracetam, and carbamazepine-levetiracetam adjunctive treatment in male Wistar rats. Toxicol Rep. 2021;8:592-598. https://doi.org/10.1016/j.toxrep.2021.03.008
Enye LA, Saka OS, Adekanye UA, Adekeye AO, Abijo AZ, Ige MS. Hippocampal Histomorphology and Biochemistry in Rats fed Diets containing Carbamazepine. Afr J Biomed Res. 2022;25(1):89-94.
Fang J, Yin H, Yang Z, Tan M, Wang F, Chen K et al. Vitamin E protects against cadmium-induced sub-chronic liver injury associated with the inhibition of oxidative stress and activation of Nrf2 pathway. Ecotoxicol Environ Saf. 2021;208:111610. https://doi.org/10.1016/j.ecoenv.2020.111610
Üremiş MM, Gültekin S, Üremiş N, Şafak T, Çiğremiş Y, Gül M, et al. Protective role of vitamin E against acrylamide-induced testicular toxicity from pregnancy to adulthood: insights into oxidative stress and aromatase regulation. Naunyn Schmiedebergs Arch Pharmacol. 2024;397(2):829-841. https://doi.org/10.1007/s00210-023-02638-8
Kharchoufa L, Bouhrim M, Bencheikh N, El Assri S, Amirou A, Yamani A, et al. Acute and subacute toxicity studies of the aqueous extract from Haloxylon scoparium Pomel (Hammada scoparia (Pomel)) by oral administration in rodents. BioMed Res Int. 2020;2020: 4020647. https://doi.org/10.1155/2020/4020647
Kwast L, Fiechter D, Kruijssen L, Bleumink R, Ludwig I, Bol-Schoenmakers M, et al. Oral exposure to immunostimulating drugs results in early changes in innate immune parameters in the spleen. J Immunotoxicol. 2016;13(4):535-547. https://doi.org/10.3109/1547691X.2016.1139643
Akinwumi KA. Vitamin E Alleviates Diethylhexyl Phthalate-Induced Haemato-logical Changes and Splenic Oxidative Injury in Male Sprague-Dawley Rats. J Can Res Updates. 2019;8(1):42-51.https://doi.org/10.30683/1929-2279.2019.08.06
Akorede GJ, Ambali SF, Olatunji AO, Aremu A, Ahmed AO, Basiru A, et al. Vitamin C Protects Against Blood and Thyroid Toxicities Induced by the Chronic Use of Carbamazepine in Rats. Iran J Toxicol. 2023;17(2):147-156. http://dx.doi.org/10.32598/IJT.17.2.1080.1
Rezaei M, Mashinchian Moradi A, Mortazavi P, Jamili S. Effects of chronic exposure to carbamazepine on hematological parameters in Cyprinus carpio. Iran J Fish Sci. 2020;19(1):443-456. https://doi.org/10.22092/IJFS.2019.119014
Xiao W, Zhou K, Yang M, Sun C, Dai L, Gu J, et al. Carbamazepine induces platelet apoptosis and thrombocytopenia through protein kinase A. Front Pharmacol. 2021;12:749930. https://doi.org/10.3389/fphar.2021.749930
Eid FA, El-Gendy M, Zahkouk SA, El-Tahway NA, El-Shamy S. Ameliorative effect of two antioxidants on the liver of male albino rats exposed to electromagnetic field. Egypt J Hosp Med. 2015;58(1):74-93.https://doi.org/10.12816/0009363
Tamura A, Miyawaki I, Yamada T, Kimura J, Funabashi H. Oral administration of drugs with hypersensitivity potential induces germinal center hyperplasia in secondary lymphoid organ/tissue in Brown Norway rats, and this histological lesion is a promising candidate as a predictive biomarker for drug hypersensitivity occurrence in humans. Toxicol Appl Pharmacol. 2013;271(1):30-40. doi: 10.1016/j.taap.2013.04.022.
Younus N, Sultana K, Ali AB. The Toxic Effects of Cyclosporine on Splenic Tissue of Rat and it’s Amelioration with Nigella Sativa. Int J Pathol. 2017: 15(2):44-50.
Mazen NF, Saleh EZ, Mahmoud AA, Shaalan AA. Histological and immunohistochemical study on the potential toxicity of sliver nanoparticles on the structure of the spleen in adult male albino rats. Egypt J Histol. 2017;40(3):374-387. doi: 10.21608/EJH.2017.4662
Afshari-Kaveh M, Abbasalipourkabir R, Nourian A, Ziamajidi N. The protective effects of vitamins A and E on titanium dioxide nanoparticles (nTiO2)-induced oxidative stress in the spleen tissues of male Wistar rats. Biol Trace Elem Res. 2021;199:3677-3687. https://doi.org/10.1007/s12011-020-02487-z
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Pakistan Journal of Medicine and Dentistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
This is an open-access article distributed under the terms of the CreativeCommons Attribution License (CC BY) 4.0 https://creativecommons.org/licenses/by/4.0/
How to Cite
