Appropriate Dose of Standard Anti-Tuberculosis Regimen to Induce Hepatotoxicity in Mice

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Nathaphon Kuncharoenwirat
Yollada Sriset
Nadta Sukkasem
Kanokwan Jarukamjorn
Waranya Chatuphonprasert

Abstract

Introduction: The current regimen of anti-tuberculosis drugs has to combine several drugs for long period for the efficacy to eliminate infection and prevention of drugs resistance. But the most important of anti-tuberculosis drugs is hepatotoxicity. This study aimed to investigate the appropriate dose of anti-tuberculosis drug regimen in animal model for further study to develop the new compound against anti-tuberculosis toxicity. Methods: The 7-week-old male ICR mice were given standard regimen of anti-tuberculosis (Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E) at the dose of normal human 5-times (HRZE-5) and 10-times (HRZE-10) for 7 and 14 days. After that, mouse livers were collected for histopathological examination using hematoxyline and eosin staining with analyzing the activities of superoxide dismutase (SOD) and catalase (CAT). Results: The damage of hepatic tissue and the abnormality was observed after receiving anti-tuberculosis drug both of 5-times (HRZE-5) and 10-times (HRZE-10) for 7 and 14 days. Hydropic degeneration, Karyolysis and the trend to become Piecemeal necrosis of hepatic cells were observed. The hepatic SOD and CAT enzyme activities were significantly decreased in HRZE-5 and HRZE-10 groups in mice which were treated for 7 and 14 days. Conclusion: Anti-tuberculosis regimens of HRZE-5 and HRZE-10 induced the hepatotoxicity by tissue damage and reduction of activity SOD and CAT enzymes. Hence, the model in this study at 7 and 14 days is appropriate for further study about new compounds to protect hepatoxicity by anti-tuberculosis drugs. However, the investigation only SOD enzyme and CAT enzyme activity may not enough to reflect the total result of hepatic cells damage. Therefore, the hepatic histopathology is necessary to be the supported information for more accurately in showing the damage that occur in the hepatic cells.

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Pharmaceutical Sciences

References

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