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Matrine induces toxicity in mouse liver cells through an ROS-dependent mechanism
Jie Liu1, Yuwan Zhao1, Juan Xia2
1Laboratory of Urology, Guangdong Medical University, Zhanjiang, 524001, China.
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.
Insights
Matrine, a compound from Sophora flavescens, can harm mouse liver cells by increasing oxidative stress. Antioxidants may counteract this matrine-induced hepatotoxicity, suggesting reactive oxygen species (ROS) play a key role.
Area of Science:
- Pharmacology
- Toxicology
- Cell Biology
Background:
- Matrine, derived from Sophora flavescens Ait, exhibits anti-inflammatory, anti-tumor, and anti-viral properties.
- The toxicity and underlying mechanisms of matrine, particularly its effects on liver cells, require thorough investigation.
Purpose of the Study:
- To evaluate the toxicity of matrine on mouse liver cells.
- To elucidate the reactive oxygen species (ROS)-associated mechanisms involved in matrine-induced hepatotoxicity.
Main Methods:
- Mice were administered low-dose (50 mg/kg) and high-dose (100 mg/kg) matrine intraperitoneally for 7 days.
- Liver tissues were analyzed for histopathology and HO-1 expression; serum was assessed for AST and ALT activities.
- Mouse liver NCTC cells were treated with matrine to examine cell viability, apoptosis, caspase activity, ROS generation, mitochondrial membrane potential, and ATP levels.
Main Results:
- Matrine treatment led to elevated serum AST and ALT levels and vacuolar degeneration in liver tissues.
- In vitro, matrine suppressed cell viability, increased cytotoxicity and apoptosis, altered apoptotic protein expression, and activated caspases-3 and -9.
- Matrine induced ROS generation and reduced mitochondrial membrane potential and ATP levels; N-acetylcysteine reversed these effects.
Conclusions:
- Matrine induces hepatotoxicity in mouse liver cells both in vivo and in vitro.
- The findings suggest that ROS generation is a key mechanism underlying matrine-induced liver toxicity.
