Adelmidrol ameliorates liver ischemia-reperfusion injury through activating Nrf2 signaling pathway

Liver ischemia/reperfusion (I/R) injury commonly occurs after various liver surgeries. Adelmidrol, an N- palmitoylethanolamide analog, has anti-inflammatory, anti-oxidant, and anti-injury properties. To investigate whether adelmidrol could reduce liver I/R injury, we established a mouse of liver I/R injury and an AML12 cell hypoxia-reoxygenation model to perform experiments using multiple indicators. Serum ALT and AST levels, and H&E staining were used to measure liver damage; MDA content, superoxide dismutase and glutathione activities, and dihydroethidium staining were used to measure oxidative stress; mRNA expression levels of tumor necrosis factor-α, interleukin(IL)-1β, IL-6, MCP-1, and Ly6G staining were used to measure inflammatory response; and protein expression of Bax, Bcl-2, C-caspase3, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were used to measure apoptosis. The experimental results showed that adelmidrol reduced liver I/R injury. In addition, adelmidrol pretreatment elevated AML12 cell activity and reduced I/R-and H/R-induced apoptosis, inflammatory injury, and oxidative stress. ML385, an inhibitor of nuclear factor erythroid2-related factor 2 (Nrf2), reverses liver I/R injury attenuated by adelmidrol. These results suggest that adelmidrol ameliorates liver I/R injury by activating the Nrf2 signaling pathway.

 

Comments:

The study you described delves into the potential benefits of adelmidrol in reducing liver ischemia/reperfusion (I/R) injury. Adelmidrol, an analog of N-palmitoylethanolamide, has demonstrated anti-inflammatory, anti-oxidant, and anti-injury properties.

The researchers used multiple indicators to assess the effects of adelmidrol on liver I/R injury:

1. **Liver Damage**: Serum levels of ALT and AST along with histological examination using H&E staining were employed to evaluate the extent of liver damage caused by I/R.

2. **Oxidative Stress**: Measurement of MDA content, superoxide dismutase, and glutathione activities, as well as dihydroethidium staining, were utilized to assess oxidative stress levels in the liver.

3. **Inflammatory Response**: mRNA expression levels of inflammatory markers like tumor necrosis factor-α, interleukins (IL-1β, IL-6), MCP-1, and Ly6G staining were used to gauge the inflammatory response in the liver.

4. **Apoptosis**: Protein expression levels of Bax, Bcl-2, C-caspase3, and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining were examined to measure apoptosis.

The results indicated that adelmidrol reduced liver I/R injury. Moreover, adelmidrol pretreatment increased the activity of AML12 cells and lessened both I/R and hypoxia-reoxygenation-induced apoptosis, inflammatory injury, and oxidative stress.

Interestingly, the study found that ML385, an inhibitor of the nuclear factor erythroid2-related factor 2 (Nrf2), reversed the liver I/R injury attenuation caused by adelmidrol. This suggests that adelmidrol's mechanism of action involves the activation of the Nrf2 signaling pathway, which plays a crucial role in cellular defense against oxidative stress.

This research provides valuable insights into the potential therapeutic use of adelmidrol for mitigating liver I/R injury, possibly through the Nrf2 pathway activation.

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