Mouse hepatotoxicity model by the anti-tuberculosis regimen
Nathaphon Kuncharoenwirat1, Yonlada Sriset2, Kanokwan Jarukamjorn3, Waranya
Chatuphonprasert4
1
Undergraduate student (Pharm. D. Program), Faculty of Pharmaceutical Sciences, Khon
Kaen University
2
Graduate student (M.Sc. Program in Health Science), Faculty of Medicine, Mahasarakham
University
3
Associate Professor, Research Group for Pharmaceutical Activities of Natural Products
using Pharmaceutical Biotechnology (PANPB), Faculty of Pharmaceutical Sciences, Khon
Kaen University
4
Lecturer, Department of Pre-clinic, Faculty of Medicine, Mahasarakham University
Introduction: Tuberculosis (TB) is an important infectious disease in developing countries.
Anti-tuberculosis regimen combines at least four drugs in order to prevent the mycobacterial
resistance. The most important side effect of anti-tuberculosis drugs is hepatotoxicity. This
study aimed to examine how the anti-tuberculosis regimen affected on liver tissue and
glutathione profile in the mouse livers.
Materials and Method: Seven-week-old male ICR mice were orally administered the antituberculosis regimen containing two different doses of four drugs, namely Anti-TB5
(isoniazid 30 mg/kg/day + rifampicin 60 mg/kg/day + pyrazinamide 100 mg/kg/day +
ethambutol 125 mg/kg/day), and Anti-TB10 (isoniazid 60 mg/kg/day + rifampicin 120
mg/kg/day + pyrazinamide 200 mg/kg/day + ethambutol 250 mg/kg/day), daily for two
weeks. Both regimens were of five- and ten-fold of the normal dosage regimen in human. The
control mice were simply given the vehicle (0.1 mL of 0.5% carboxymethyl cellulose). At 24
hour after the last treatments, the livers were collected for histomorphological examination by
hematoxylin and eosin (H&E) staining and determination of glutathione profile.
Results: The control mice showed normal hepatic histomorphology while Anti-TB5 and
Anti-TB10 markedly induced hepatic cell swelling and death. Total glutathione, reduced
glutathione (GSH), and oxidized glutathione (GSSG) contents were significantly depleted by
Anti-TB5 and Anti-TB10 regimens.
Conclusion: The treatments with Anti-TB5 or Anti-TB10 regimens for two weeks were
potentially induced hepatotoxicity in the mice by suppression of the glutathione profile and
causing the cell death. This model is useful for further investigation of a new hepatoprotective compound.
Keywords: Anti-tuberculosis drug, hepatic injury, histomorphology, glutathione
*
Corresponding author: Faculty of Medicine, Mahasarakam University, Tel: 043-754121
Fax: 043-754121, E-mail: waranya.c@msu.ac.th