Methotrexate Induced Hepatotoxicity and its Management

Liver dysfunction is a major health problem that challenges not only health care professionals but also the pharmaceutical industry and drug regulatory agencies. Commonly used drugs such as anti cancer drugs, certain antibiotics, antituberculer agents, paracetamol and various other toxic chemicals such as carbon tetrachloride (CCL4), thioacetamide (TAA), excessive alcohol consumption, arsenic and microbes reported to cause hepatotoxicity. In addition to this, genetics, metabolism and immunology also played important role in hepatotoxicity. Methotrexate is commonly used as anticancer and immunosuppressant drug. Its major side effects are bone marrow depression and hepatotoxicity. In the present review, we discuss about the mechanism of methotrexate induced hepatotoxicity and its herbal based treatment. Mechanism of methotrexate induced hepatotoxicity includes oxidative stress which increase the generation of reactive oxygen (ROS) and nitrogen species, inhibits cytosolic NADP-dependent dehydrogenase and NADP malic enzyme, which reduce the levels of glutathion, superoxide dismutase, catalase and ultimately reducing the effectivity of the antioxidant defence system protecting the cell against ROS. Herbal medicines may serve as a vital source of potentially useful for the development of effective therapy to combat a variety of liver problems. Developing a satisfactory herbal therapy to treat severe liver diseases requires systematic investigation of properties like anti-hepatotoxicity and stimulation of liver regeneration.