Potential Liver Toxicity of X54 is Educed Under Pre-existing Inflammatory Conditions in a Murine Model

Some herbal medicines have gained a significant popularity as they are perceived safe and acceptable treatment modalities for various ailments including chronic liver disease, but this notion should be tested precisely in normal and preconditioned inflammatory conditions [1]. In vitro microsome studies are used to predict in vivo hepatic clearances for some compounds; however, numerous failed attempts have been reported. In vivo studies are, therefore, necessary to complement the in vitro studies. We tested X54, an herbal compound extracted at NCNPR, in CD-1 mice for liver toxicity. Eight or six hours after LPS and X54 respectively, the animals were sacrificed and blood was collected for enzyme assays, which were performed using commercially available kits. At 1.25 mg/kg intraperitoneally, mice showed no-observed-adverse-effect-level (NOAEL) in terms of liver toxicity evaluated by plasma alanine transaminase (ALT) units compared to negative control. When given 2 hours post LPS (0.75 mg/kg) treatment, X54 showed a substantial increase in ALT level compared to normal while LPS (0.75 mg/kg) alone did not deviate from ALT level in controls. We concluded that exposure to a small dose of LPS can apparently render the liver more prone to injury from herbal drugs by decreasing the threshold of toxicity and/or increasing the magnitude of response. Preconditioning the mice with a low dose of LPS followed by X54 injection elicits a mild liver toxicity, X54 at the dose used in this study caused a NOAEL regarding liver toxicity. The model used here is a sensitive indicator for testing herbal products for their potential of causing liver injury. Acknowledgements: Thanks go to Mrs Lavanya Madgula in NCNPR for running the blood chemistry analysis of liver enzymes. References: [1] Stickel F, et al. (2005) Journal of Hepatology 43: 901–910.