Matrine induces toxicity in mouse liver cells through an ROS-dependent mechanism

Abstract

Matrine is major active component in Sophora flavescens Ait that plays pharmacological activities against inflammation, tumors and virus. However, potential toxicity of matrine and its possible toxic mechanisms have not been carefully studied. The aim of the study is to assess the toxicity of matrine on mouse liver cells and to investigate the potential ROS-associated mechanisms. Mice were randomly divided into three groups: vehicle control (normal saline), low-dose (50 mg/kg), and high dose (100 mg/kg) groups. Mice in each group were intraperitoneally injected with matrine daily for 7 d. The livers were collected for analysis of histopathological changes and HO-1 protein expression. Serum was collected for analysis of aspartate aminotransferase and alanine aminotransferase activities. Mouse liver NCTC cells were treated with matrine for certain time, and cell viability, cytotoxicity, apoptosis, expression of proteins, activities of caspase-3 and caspase-9, and levels of ROS generation, mitochondrial membrane potential, and ATP were examined. Increased activities of AST and ALT in serum, and vacuolar degeneration of cytoplasm in liver tissues were observed after treatment. Suppression of cell viability, increase of cytotoxicity, induction of apoptosis, alteration in the expression of apoptotic-related proteins, and activation of caspase-3 and caspase-9 were shown in matrine-treated NCTC cells. Furthermore, matrine induced ROS generation, and suppressed mitochondrial membrane potential and ATP levels, however, the antioxidant N-acetylcysteine reversed matrine-induced hepatotoxicity and ROS generation. These findings suggested that matrine stimulated the generation of ROS, which was possibly involved in matrine-induced toxicity in mouse liver cells in vitro and in vivo.