LAUSR

As a serious infectious disease, tuberculosis threatens global public health. Isoniazid is the first‐line drug not only in active tuberculosis but also in its prevention. Severe hepatotoxicity greatly limits its use. Curcumin, extracted from turmeric, has been found to relieve isoniazid‐induced hepatotoxicity. However, the mechanism of isoniazid‐induced hepatotoxicity and the protective effects of curcumin are not yet understood completely. We established both cell and animal models about isoniazid‐induced hepatotoxicity and investigated the new mechanism of curcumin against isoniazid‐induced liver injury. The experimental data in our study demonstrated that curcumin ameliorated isoniazid‐mediated liver oxidative stress. The protective effects of curcumin were demonstrated and confirmed to be correlated with upregulating SIRT1/PGC‐1α/NRF1 pathway. Western blot revealed that while inhibiting SIRT1 by the siRNA1 (a SIRT1 inhibitor), the expressions of SIRT1, PGC‐1α/Ac‐PGC‐1α, and NRF1 decreased, and the protective effect that curcumin exerted on isoniazid‐treated L‐02 cells was significantly attenuated. Furthermore, curcumin improved liver functions and reduced necrosis of the isoniazid‐treated BALB/c mice, accompanied by downregulating oxidative stress and inflammation in liver. Western blot revealed that curcumin treatment activates the SIRT1/PGC‐1α/NRF1 pathway in the isoniazid‐treated BALB/c mice. In conclusion, we found one mechanism of isoniazid‐induced hepatotoxicity downregulating the SIRT1/PGC‐1α/NRF1 pathway, and curcumin attenuated this hepatotoxicity by activating it. Our study provided a novel approach and mechanism for the treatment of isoniazid‐induced hepatotoxicity.