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Exposure to hydrogen peroxide induces cell death via apoptosis in primary cultured mouse hepatocytes
S Kanno1, M Ishikawa, M Takayanagi
1Department of Pharmacology and Toxicology, Tohoku Pharmaceutical University, Sendai, Japan.
Abstract:
To investigate whether direct oxidant damage induces hepatotoxicity via an apoptotic cell suicide pathway, we exposed primary cultured mouse hepatocytes to pro-oxidant hydrogen peroxide. We demonstrate that brief exposure to a concentration of hydrogen peroxide (3 mM) can induce hepatocyte cell death via apoptosis as shown by toxicity assays, specific DNA staining, and the appearance of DNA laddering on agarose gels. When hepatocytes were treated with N-acetylcysteine 15 min prior to hydrogen peroxide exposure, the cells were found to be protected from cytotoxicity and apoptosis. These results suggest that direct oxidative injury serves as a general trigger for apoptosis in the liver, and that other apoptotic stimuli, such as exposure to acetaminophen, also involve oxidative injury. Hydrogen peroxidase-induced apoptosis may serve as a valuable model for further studies of apoptosis in the liver.
Insights
Direct oxidant damage from hydrogen peroxide induces liver cell death through apoptosis. N-acetylcysteine protected liver cells, suggesting oxidative injury triggers liver apoptosis.
Area of Science:
- Hepatology
- Toxicology
- Cell Biology
Background:
- Oxidant damage is implicated in liver injury.
- The role of apoptosis in oxidant-induced hepatotoxicity requires further elucidation.
Purpose of the Study:
- To investigate if direct oxidant damage induces hepatotoxicity via apoptosis.
- To explore the protective effects of N-acetylcysteine against oxidant-induced apoptosis.
Main Methods:
- Primary cultured mouse hepatocytes were exposed to hydrogen peroxide.
- Apoptosis was assessed using toxicity assays, DNA staining, and DNA laddering.
- N-acetylcysteine was used as a protective agent.
Main Results:
- Hydrogen peroxide (3 mM) induced hepatocyte cell death via apoptosis.
- N-acetylcysteine pretreatment protected hepatocytes from hydrogen peroxide-induced cytotoxicity and apoptosis.
- These findings indicate direct oxidative injury triggers liver apoptosis.
Conclusions:
- Direct oxidative injury is a significant trigger for apoptosis in liver cells.
- Hydrogen peroxide-induced apoptosis serves as a model for studying liver apoptosis.
- Oxidative injury may be involved in other apoptotic stimuli like acetaminophen exposure.