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Updated: Feb 26, 2026
Murine Model of Metastatic Liver Tumors in the Setting of Ischemia Reperfusion Injury
Published on: August 30, 2019
Treatment with dimethyl fumarate ameliorates liver ischemia/reperfusion injury
Chie Takasu1, Nosratola D Vaziri1, Shiri Li1
1Chie Takasu, Nosratola D Vaziri, Shiri Li, Lourdes Robles, Kelly Vo, Mizuki Takasu, Christine Pham, Seyed H Farzaneh, Michael J Stamos, Hirohito Ichii, Department of Surgery, Medicine, University of California, Irvine, CA 92868, United States.
Aim:
To investigate the hypothesis that treatment with dimethyl fumarate (DMF) may ameliorate liver ischemia/reperfusion injury (I/RI).
Methods:
Rats were divided into 3 groups: sham, control (CTL), and DMF. DMF (25 mg/kg, twice/d) was orally administered for 2 d before the procedure. The CTL and DMF rats were subjected to ischemia for 1 h and reperfusion for 2 h. The serum alanine aminotransferase (ALT) and malondialdehyde (MDA) levels, adenosine triphosphate (ATP), NO × metabolites, anti-oxidant enzyme expression level, anti-inflammatory effect, and anti-apoptotic effect were determined.
Results:
Histological tissue damage was significantly reduced in the DMF group (Suzuki scores: sham: 0 ± 0; CTL: 9.3 ± 0.5; DMF: 2.5 ± 1.2; sham vs CTL, P < 0.0001; CTL vs DMF, P < 0.0001). This effect was associated with significantly lower serum ALT (DMF 5026 ± 2305 U/L vs CTL 10592 ± 1152 U/L, P = 0.04) and MDA (DMF 18.2 ± 1.4 μmol/L vs CTL 26.0 ± 1.0 μmol/L, P = 0.0009). DMF effectively improved the ATP content (DMF 20.3 ± 0.4 nmol/mg vs CTL 18.3 ± 0.6 nmol/mg, P = 0.02), myeloperoxidase activity (DMF 7.8 ± 0.4 mU/mL vs CTL 6.0 ± 0.5 mU/mL, P = 0.01) and level of endothelial nitric oxide synthase expression (DMF 0.38 ± 0.05-fold vs 0.17 ± 0.06-fold, P = 0.02). The higher expression levels of anti-oxidant enzymes (catalase and glutamate-cysteine ligase modifier subunit and lower levels of key inflammatory mediators (nuclear factor-kappa B and cyclooxygenase-2 were confirmed in the DMF group.
Conclusion:
DMF improved the liver function and the anti-oxidant and inflammation status following I/RI. Treatment with DMF could be a promising strategy in patients with liver I/RI.
Insights
Dimethyl fumarate (DMF) significantly reduced liver injury in a rat model of ischemia/reperfusion injury (I/RI). DMF treatment improved liver function and reduced oxidative stress and inflammation, suggesting its therapeutic potential for I/RI.
Area of Science:
- Hepatology
- Pharmacology
- Surgical Research
Background:
- Liver ischemia/reperfusion injury (I/RI) is a significant clinical challenge.
- Current therapeutic strategies for I/RI have limitations.
Purpose of the Study:
- To investigate the therapeutic potential of dimethyl fumarate (DMF) in ameliorating liver I/RI.
- To evaluate the effects of DMF on liver function, oxidative stress, and inflammation markers.
Main Methods:
- A rat model of liver I/RI was established.
- Rats were treated with dimethyl fumarate (DMF) or vehicle control.
- Liver damage, serum enzyme levels, oxidative stress markers, and inflammatory mediators were assessed.
Main Results:
- DMF treatment significantly reduced histological liver damage and serum ALT levels.
- DMF administration decreased malondialdehyde (MDA) levels and improved ATP content.
- DMF treatment upregulated antioxidant enzyme expression and downregulated inflammatory mediators.
Conclusions:
- Dimethyl fumarate (DMF) demonstrates significant protective effects against liver ischemia/reperfusion injury (I/RI).
- DMF improves liver function and modulates oxidative stress and inflammation.
- DMF represents a promising therapeutic strategy for managing liver I/RI.
