HISTOLOGIC EFFECTS OF ISONIAZID ON THE LIVER OF ALBINO MICE
PDF

Supplementary Files

Histologic effects of isoniazid induced hepatotoxicity in male albino mice

How to Cite

Humayun, F., Tahir, M., & Lone, K. P. (2017). HISTOLOGIC EFFECTS OF ISONIAZID ON THE LIVER OF ALBINO MICE. KHYBER MEDICAL UNIVERSITY JOURNAL, 9(2). Retrieved from https://www.kmuj.kmu.edu.pk/article/view/15829

Abstract

ABSTRACT

OBJECTIVE: to investigate the effects of thirty days of isoniazid administration on histomorphology of adult male albino mice liver.  

METHODS: Forty healthy adult male mice were obtained from the Veterinary Research Institute Lahore and were kept in the animal house facility of University of Health Sciences Lahore. Animals were fed on normal mouse diet and water ad libitum. Mice were divided into two groups, i.e. group A & B. Group A served as a control and received 10ml/kg of distilled water while group B served as experimental and treated with isoniazid 100mg/kg body weight for 30 days. At the end of the experiment liver was dissected and processed for light microscopy. Serial sections of liver 4µm thick were stained with Harris Hematoxylin & Eosin and Periodic Acid Schiff (PAS) for microscopic examination.

RESULTS: No obvious gross abnormalities were present in either control or experimental group. Group A showed the normal liver histology. Group B showed disturbed liver architecture with loss of radial arrangement of hepatic cords and sinusoids. Hepatocyte boundaries were ill-defined. Darkly stained nuclei indicating pyknotic changes. Necrosis evident by pyknosis, karyolysis and karyorrhexis was also observed. Apoptotic bodies were clearly seen and fatty change was evident by signet ring formation. Larger, swollen and empty looking hepatocytes, with the loss of cytoplasmic contents appearing as micro and macro vacuoles were noticed. Vessels were dilated and congested. Periportal and focal areas of inflammation were present.

CONCLUSION: Isoniazid treatment has potential hepatotoxic effects on male albino mice causing disturbed liver architecture.

Key words: Isoniazid (MeSH), Necrosis (MeSH), Apoptosis (MeSH), hepatotoxic (Non-MeSH), Antitubercular Agents (MeSH).

PDF

References

REFERENCES

Maryam S, Aziz K, Bhatti ASA, Shahzad AW. Effects of jetepar (glucometamine, glucodiamine and nicotinamide ascorbate) on isoniazid induced hepatotoxicity in rabbits. Annuals 2010;16(1):37-42.

Sekai C, Carla AW, Charles AP, William ZB, Philip CH, Charles DW, et al. Isoniazid, Rifampin, Ethambutol, and Pyrazinamide Pharmacokinetics and Treatment Outcomes Among a Predominantly HIV-Infected Cohort of Adults with Tuberculosis from Botswana. Clin Infect Dis 2009;48(12):1685-94.

Khan SR, Morgan AG, Michail K, Srivastava N, Whittal RM, Aljuhani N, et al. Metabolism of isoniazid by neutrophil myeloperoxidase leads to isoniazid-NAD+ adduct formation: a comparison of the reactivity of isoniazid with its known human metabolites. Biochem Pharmacol 2016;106:46–55. doi: 10.1016/j.bcp.2016.02.003. Epub 2016 Feb 9.

Steven TP, Jon CA, Rebecca D, Kim AH, Rose EJ, Charlotte LHD, et al. The effect of growth rate on pyrazinamide activity in Mycobacterium tuberculosis - insights for early bactericidal activity. BMC Infect Dis 2016;16(1):205.

Horsburgh JCR, Barry CE, Lange C. Treatment of tuberculosis. N Engl J Med 2015 Nov 26;373(22):2149-60. doi: 10.1056/NEJMra1413919.

Villarino ME, Scott NA, Weis SE, Weiner M, Conde MB, Jones B, et al. The International Maternal Pediatric and Adolescents AIDS Clinical Trials Group (IMPAACT) and the Tuberculosis Trials Consortium (TBTC). Treatment for Preventing Tuberculosis in Children and Adolescents. A Randomized Clinical Trial of a 3-Month, 12-Dose Regimen of a Combination of Rifapentine and Isoniazid. JAMA Pediatr 2015;169(3):247-55.

Kalra BS, Aggarwal S, Khurana N, Gupta U. Effect of cimetidine on hepatotoxicity induced by isoniazid-rifampicin combination in rabbits. Indian J Gastroenterol 2007;26(1):18-21.

Tostmann A, Boeree MJ, Aarnouts RE, Dekhuijzen R. Antituberculosis drug – induced hepatotoxicity. J Gastroenterol Hepatol 2008;23(2):192-202.

Jehangir A, Nagi AH, Shahzad M, Zia A. The hepatoprotective effect of Cassia fistula (amaltas) leaves in isoniazid and rifampicin induced hepatotoxicity in rodents. Biomedica 2010;26(1):25–9.

Jahan S, Khan M, Imran S, Sair M. The hepatoprotective role of Silymarin in isoniazid induced liver damage of rabbits. J Pak Med Assoc 2015 Jun 1;65(6):620-3.

Rao GN, Lindamood C, Heath JE, Farnell DR, Giles HD. Sub chronic toxicity of human immunodeficiency virus and tuberculosis combination therapies in B6C3F1 Mice. Toxicol Sci 1998;45(1):113-27.

Cynamon MH, Sklaney M. Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis. Antimicrob Agents Chemother 2003;47(8):2442–4.

Bigoniya P, Singh CS, Shukla A. A comprehensive review of different liver toxicants used in experimental pharmacology. Int J Pharm Sci Drug Res 2009;1(3):124-35.

Noorani AA, Saini N, Saini K, Kale MK. Hepatoprotective effect of rimonabant against isoniazid induced liver damage in albino wistar rats. Int J Pharm Biol Sci Arch 2010;1(05):473-7.

Bhadauria M, Nirala SK, Shukla S. Hepatoprotective efficacy of propolis extract: A biochemical and histopathological approach. Int J Pharm Technol 2007;6(2):145-54.

Sambrekar SN, Patil PA, Kangralkar VA. Protective effect of Embelia Tsjeriam – Cottam fruit extracts on isoniazid induced hepatotoxicity in wistar rats. Int J Pharm Sci Res 2010;4(1):136-9.

Kalra BS, Aggarwal S, Khurana N, Gupta U. Effect of cimetidine on hepatotoxicity induced by isoniazid-rifampicin combination in rabbits. Indian J Gastroenterol 2007;26(1):18-21.

Tandon VR, Khajuria V, Kapoor B, Kour D, Gupta S. Hepatoprotective activity of Vitex negundo leaf extract against anti-tubercular drugs induced hepatoxicity. Fitoterapia 2008;79(7):533-8.

Kale BP, Kothekar MA, Tayade HP, Jaju JB, Mateen-ud-Din M. Effect of aqueous extract of azadirachta indica leaves on hepatotoxicity induced by anti-tubercular drugs in rats. Indian J Pharmacol 2003;35(3):177-80.

Pal R, Vaiphei K, Sikander A, Singh K, Rana SV. Effect of garlic on isoniazid and rifampicin – induced hepatic injury in rats. World J Gastroenterol 2006;12(4):636-9.

Anbarasu C, Rajkapoor B, Kalpana J. Protective effect of Pisonia aculeate on rifampicin and isoniazid induced hepatotoxicity in rats. Inter J Phytomed 2011;3(1):75- 83.

Work published in KMUJ is licensed under a

 Creative Commons Attribution-NonCommercial 2.0 Generic License.

Creative Commons License

Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work.