Similar hepatotoxicity response induced by Rhizoma Paridis in zebrafish larvae, cell and rat

Rhizoma Paridis, as a Traditional Chinese Medicine (TCM), has been used in clinic for thousands of years. Recently, the hepatic toxicity was reported in some published articles while its hepatotoxicity mechanisms have not been well established. Therefore, the present study was performed to determine the effect of Rhizoma Paridis treatment on the lipid deposition and metabolism, oxidative stress and mitochondrial dysfunction, and explore the underlying molecular mechanism through L02 cell, rat and zebrafish larvae. Rhizoma Paridis could diminish cell activity and cell proliferation, brought on cell apoptosis and elevated the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared with the control group, as evaluated in cell cultures. Rhizoma Paridis could result in the change of the liver structure and the liver function in the rat model and zebrafish larvae. Our results showed that Rhizoma Paridis could increase hepatic lipid accumulation, which was similar to the previous study and probably exerted toxic effect through intensive fatty acid lipogenesis, inhibition of fat degradation. Meanwhile, this experiment highlighted the importance of the oxidative stress, mitochondrial dysfunction, ER function, and the inflammation response in Rhizoma Paridis-induced disorder of hepatic lipid metabolism, which proposed a novel mechanism for interpretation of Rhizoma Paridis exposure inducing the disorder of lipid metabolism in vertebrates. Furthermore, the result of this experiment suggested that the toxicity response of zebrafish larvae was similar to the conventional model with a significant advantage.