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Experimental Protocol for Detecting Mitochondrial Function in Hepatocytes Exposed to Organochlorine Pesticides
Published on: September 16, 2020
Mitochondrial-targeted ubiquinone alleviates concanavalin A-induced hepatitis via immune modulation
Yemane Tadesse Desta1, Mi Wu1, Li Bai2
1Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, 430030 Wuhan, China.
Background:
Despite knowledge regarding the effects of antioxidants in ameliorating oxidative damage, evidence concerning their effects on activated immune cells is lacking. Here, a concanavalin A (Con A)-induced hepatitis mouse model was used to investigate the protective effects and immune regulatory mechanisms of mitochondrial-targeted ubiquinone (MitoQ).
Methods:
Wild-type (WT) and CD1d-knockout (CD1d-/-, NKT cell deficient) mice were pretreated with MitoQ and then intravenously injected with a sublethal dose of Con A. Serum transaminase and inflammatory cytokine levels were tested. Immune cell functions and AMPK/mTORC1 pathway activation in liver tissue were also evaluated.
Results:
NKT cells were critical for extensive pro-inflammatory cytokine production and prolonged liver injury upon Con A challenge, while IFN-γ-producing non-NKT cells played an important role during the hyperacute phase. MitoQ treatment not only ameliorated NKT cell-independent hyperacute hepatitis within 12 h post Con A administration but also alleviated NKT cell-dependent extended liver injury at 24 h. The underlying mechanisms involved an inhibition of the heightened activation of iNKT cells and conventional T cells, suppression of the excessive production of IFN-γ, TNF-α and IL-6, and modulation of aberrant AMPK and mTORC1 pathways.
Conclusion:
MitoQ efficiently alleviates Con A-induced hepatitis through immune regulation, suggesting a new therapeutic approach for immune-mediated liver injury by targeting mitochondrial ROS.
Insights
Mitochondrial-targeted ubiquinone (MitoQ) protects against concanavalin A (Con A)-induced liver injury by regulating immune cells and inflammatory pathways. This antioxidant offers a potential new therapy for immune-mediated liver damage.
Area of Science:
- Immunology
- Hepatology
- Mitochondrial Medicine
Background:
- Antioxidants are known to reduce oxidative damage, but their impact on activated immune cells remains unclear.
- Investigating the role of mitochondrial-targeted ubiquinone (MitoQ) in immune-mediated liver injury.
- Utilizing a concanavalin A (Con A)-induced hepatitis mouse model to explore MitoQ's protective effects.
Purpose of the Study:
- To investigate the immune regulatory mechanisms and protective effects of MitoQ in Con A-induced hepatitis.
- To determine the role of NKT cells and other immune cells in Con A-induced liver injury.
- To explore the impact of MitoQ on inflammatory pathways and immune cell activation.
Main Methods:
- Concanavalin A (Con A) challenge in wild-type and CD1d-knockout mice pretreated with MitoQ.
- Assessment of serum transaminase and inflammatory cytokine levels.
- Evaluation of immune cell function and AMPK/mTORC1 pathway activation in liver tissue.
Main Results:
- NKT cells are crucial for prolonged liver injury and pro-inflammatory cytokine production post-Con A challenge.
- MitoQ ameliorated both early NKT cell-independent and later NKT cell-dependent liver injury.
- Mechanisms include inhibition of iNKT and T cell activation, reduced cytokine production (IFN-γ, TNF-α, IL-6), and modulation of AMPK/mTORC1 pathways.
Conclusions:
- MitoQ effectively alleviates Con A-induced hepatitis via immune regulation.
- Targeting mitochondrial reactive oxygen species (ROS) with MitoQ presents a novel therapeutic strategy for immune-mediated liver injury.
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