Significant increases in the levels of liver enzymes in mice treated with anti-tuberculosis drugs

Int J Antimicrob Agents. 2005 Aug;26(2):152-8. doi: 10.1016/j.ijantimicag.2005.04.011.


Besides the long-term effectiveness of a given compound, safety is a very important feature to consider when developing new compounds for chemotherapy against tuberculosis. Reports of fatal and severe liver injury associated with rifampicin-pyrazinamide (RIF-PZA) treatment regimens for latent tuberculosis infections prompted this study to evaluate whether a mouse model has any potential as a tool to assess liver injury following extensive exposure to tuberculosis drugs. Mice were administered high doses of existing drug regimens for latent tuberculosis over a relatively short time period. Alanine aminotransferase (ALT), aspartate aminotransferase and bilirubin levels were determined after 2 weeks and 4 weeks of treatment in serum samples collected from uninfected mice as well as mice infected with Mycobacterium tuberculosis. ALT levels increased significantly after a RIF-PZA treatment regimen for 4 weeks in uninfected mice and after 2 weeks in infected mice. Bilirubin serum levels were also significantly elevated in the M. tuberculosis-infected mice after 4 weeks of RIF-PZA treatment. The data obtained indicate that changes in serum enzyme levels in mice after extensive exposure to tuberculosis drugs could be useful as an initial indicator of drug-related hepatotoxicity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alanine Transaminase / metabolism*
  • Animals
  • Antitubercular Agents / administration & dosage*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Liver / drug effects*
  • Liver / enzymology
  • Pyrazinamide / antagonists & inhibitors
  • Pyrazinamide / pharmacology*
  • Pyrazinamide / therapeutic use
  • Rifampin / pharmacology
  • Tuberculosis / drug therapy


  • Antitubercular Agents
  • Pyrazinamide
  • Alanine Transaminase
  • Rifampin