Iranian Journal of War and Public Health

eISSN (English): 2980-969X
eISSN (Persian): 2008-2630
pISSN (Persian): 2008-2622
JMERC
0.3
Volume 14, Issue 4 (2022)                   Iran J War Public Health 2022, 14(4): 367-375 | Back to browse issues page

Print XML PDF HTML Full-Text (HTML)

History

How to cite this article
Kareem D, Sadoon A, Majeed M, Abbas B. Histological and Enzymatic Response of Carbamazepine-induced Liver Injury as A Biomarker in Male Mice. Iran J War Public Health 2022; 14 (4) :367-375
URL: http://ijwph.ir/article-1-1252-en.html
Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Rights and permissions
1- College of Veterinary Medicine, University of Basrah, Basrah, Iraq
* Corresponding Author Address: (duha.adel@uobasrah.edu.iq)
Abstract   (609 Views)
Aims: Synthetic drug-induced liver injury is the main concern of many pharmaceutical companies to obtain drugs with high safety level through continuous development in the international clinical treatment industry. Carbamazepine is one of the safest drugs for its users, but it has been found that some of these patients may develop cases of acute hepatitis. This study aimed to investigate the side effects of carbamazepine in liver injury and to elucidate the mechanism of liver toxicity caused by carbamazepine in mice.
Materials & Methods: Twenty-four mature male Balb-C mice (Mus musculus) were divided into three groups, each group containing 8 animals: The control group was given 1 ml of normal saline for 30 days, Group II received 2.85 mg/kg/day of Carbamazepine for 30 days, and Group III received 5.7 mg/kg/day of Carbamazepine during 30 days. Then, histological and enzymatic changes were evaluated. Data were analyzed using one-way ANOVA and LSD test.
Findings: Histological evaluation showed severe liver damage and acute inflammation of the liver tissue in mice that received oral carbamazepine. The serum level of liver enzymes and coenzymes showed a significant increase compared to the control group (p≤0.05).
Conclusion: Biomarkers can be used as a warning about the pre-sensitivity of some patients to carbamazepine. Also, carbamazepine treatment may change the capacity of the liver to detoxify many toxic compounds.
 
Keywords:

References
1. Park BK, Kitteringham NR, Powell H, Pirmohamed M. Advances in molecular toxicology-towards understanding idiosyncratic drug toxicity. Toxicology. 2000;153(1-3):39-60. [Link] [DOI:10.1016/S0300-483X(00)00303-6]
2. Hollander P, Gupta A, Plodkowski R, Greenway F, Bays H. Effects of naltrexone sustained-release bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36(12): 4022-9. [Link] [DOI:10.2337/dc13-0234]
3. Schlienger RG, Shear NH. Antiepileptic drug hypersensitivity syndrome. Epilepsia. 1998;39 Suppl 7:S3-7. [Link] [DOI:10.1111/j.1528-1157.1998.tb01678.x]
4. Björnsson E, Olsson R. Outcome and prognostic markers in severe drug-induced liver disease. Hepatology. 2005;42(2):481-9. [Link] [DOI:10.1002/hep.20800]
5. Bjornsson E. Hepatotoxicity associated with antiepileptic drugs. Acta Neurol Scand. 2008;118(5):281-90. [Link] [DOI:10.1111/j.1600-0404.2008.01009.x]
6. Lu W, Uetrecht JP. Peroxidase-mediated bioactivation of hydroxylated metabolites of carbamazepine and phenytoin. Drug Metab Dispos. 2008;36(8):1624-36. [Link] [DOI:10.1124/dmd.107.019554]
7. Pirmohamed M, Kitteringham NR, Guenthner TM, Breckenridge AM, Park BK. An investigation of the formation of cytotoxic, protein-reactive and stable metabolites from carbamazepine in vitro. Biochem Pharmacol. 1992;43(8):1675-82. [Link] [DOI:10.1016/0006-2952(92)90696-G]
8. Jaeschke H, Gores GJ, Cederbaum AI, Hinson JA, Pessayre D, Lemasters JJ. Mechanisms of hepatotoxicity. Toxicol Sci. 2002;65(2):166-76. [Link] [DOI:10.1093/toxsci/65.2.166]
9. Mitchell JR, Jollow DJ, Potter WZ, Gillette JR, Brodie BB. Acetaminophen-induced hepatic necroses. IV. Protective role of glutathione. J Pharmacol Exp Ther. 1973;187(1):211-7. [Link]
10. Suojanen JN, Gay RJ, Hilf R. Influence of estrogen on glutathione levels and glutathione-metabolizing enzymes in uteri and R3230AC mammary tumors of rats. Biochim Biophys Acta. 1980;630(4):485-96. [Link] [DOI:10.1016/0304-4165(80)90003-3]
11. Habig W, Pabs TM, Jakoby W. Glutathione S-transferases. The rest enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-9. [Link] [DOI:10.1016/S0021-9258(19)42083-8]
12. Luna LG. Manual of histologic staining methods of the armed forces institute of pathology. 3rd Edition. Blakiston Division, McGraw-Hill, New York: Blakiston Division, McGraw-Hill; 1968. [Link]
13. Mullick FG, Ishak KG. Hepatic injury associated with diphenyllhydantoin therapy: A clinicopahtological study of 20 cases. Am J Clin Pathol.71980;74(4):442-52. [Link] [DOI:10.1093/ajcp/74.4.442]
14. O'Hare JA, Duggan B, O'Driscoll D, Callaghan N. Biochemical evidence for osteomalacia with carbamazepine therapy. Acta Neurol Scand. 1980;62(5):282-6. [Link] [DOI:10.1111/j.1600-0404.1980.tb03037.x]
15. Friedrich M-E, Akimova E, Huf W, Konstantinidis A, Papageorgiou K, Winkle D, et al. Drug-induced liver injury during antidepressant treatment: Results of AMSP, a drug surveillance program. Int J Neuropsychopharmacol. 2016;19(4):pyv126. [Link] [DOI:10.1093/ijnp/pyv126]
16. Cepelak I, Grubisic TZ, Mandusic A, Rekic B, Lenicek J. Valproate and carbamazepine communication changes hepatic enzyme activities in the sera of epileptic children. Clin Chim Acta. 1998;276(2):121-7. [Link] [DOI:10.1016/S0009-8981(98)00094-1]
17. Benedetti MS, Ruty B, Baltes E. Induction of endogenous pathways by antiepileptics and clinical implications. Fundam Clin Pharmacol. 2005;19(5):511-29. [Link] [DOI:10.1111/j.1472-8206.2005.00341.x]
18. Driefus FE, Langer DH. Hepatic considerations in the use of antiepileptic drugs. Epilepsia. 1987;28 Suppl 2:S23-9. [Link] [DOI:10.1111/j.1528-1157.1987.tb05768.x]
19. Pearce RE, Lu W, Wang Y, Uetrecht JP, Correia MA, Leeder JS. Pathways of carbamazepine bioactivation in vitro. III. The role of human cytochrome P450 enzymes in the formation of 2,3-dihydroxycarbamazepine. Drug Metab Dispos. 2008;36(8):1637-49. [Link] [DOI:10.1124/dmd.107.019562]
20. Pearce RE, Vakkalagadda GR, Leeder JS. Pathways of carbamazepine P450 responsible for the formation of 2- and 3-hydroxylated metabolites. Drug Metab Dispos 2002;30(11):1170-9. [Link] [DOI:10.1124/dmd.30.11.1170]
21. Boyer TD, Kenney WCm Zakim D. Structural, functional and hybridization studies of the glutathione S-transferases of rat liver. Biochem Pharmacol. 1983;32(12):1843-50. [Link] [DOI:10.1016/0006-2952(83)90048-5]
22. Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 1985;57:357-417. [Link] [DOI:10.1002/9780470123034.ch5]
23. Sato K. Glutathione transferasesas markers of preneoplasia and neoplasia. Adv Cancer Res. 1989;52:205-55. [Link] [DOI:10.1016/S0065-230X(08)60214-6]
24. Gram L, Bensten KD. Hepatic toxicity of antiepileptic drugs: a review. Acta Neurol Scand Suppl. 1983;63:81-90. [Link] [DOI:10.1111/j.1600-0404.1983.tb01537.x]
25. Davion T, Capron JP, Andrejak M, Geoffroy P, Capron-Chivrac D, Quénum C. Acute hepatitis due to carbamazepine (Tegretol). Study of a case and review of the literature. Gastroenterol Clin Biol. 1984;8(1):52-6. [French] [Link]
26. Jeavons PM. Hepatotoxicity of antiepileptic drugs In: Oxley J, Janz D, Meinardi H, editors. Antiepileptic Therapy: Chronic toxicity of antiepileptic drugs. New York: Raven Press; 1983. [Link]

Add your comments about this article : Your username or Email:
CAPTCHA