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Corynoline alleviates renal ischemia-reperfusion injury by enhancing Nrf2/HO-1 pathway
1Inner Mongolia Medical University - Affiliated Hospital Hohhot - Department of Urology - Inner Mongolia Autonomous Region - China.
Purpose:
The potential of corynoline in ameliorating oxidative stress and inflammatory responses has been extensively demonstrated across various diseases. However, its specific role in the context of renal ischemia-reperfusion (IR) injury remains elusive. The aim of this study was to investigate the role of corynoline in renal IR injury and its mechanism.
Methods:
A rat model of renal IR injury was successfully developed. Samples of kidney tissue and blood were obtained to evaluate alterations in tissue damage, inflammatory response, oxidative stress, and apoptosis.
Results:
Corynoline significantly reduced renal IR injury, thus leading to improved renal function and mitigated tissue structure damage and cell apoptosis. Moreover, corynoline effectively suppressed the oxidative stress and inflammatory response induced by IR by increasing the superoxide dismutase (SOD) content, reducing the malondialdehyde (MDA) level, inhibiting neutrophil infiltration, and suppressing the release of proinflammatory cytokines. Mechanistically, corynoline successfully restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), which were significantly inhibited during renal IR injury. Furthermore, when coadministered with ML-385 (an Nrf2 inhibitor), the protective effect of corynoline against renal IR injury was counteracted.
Conclusion:
Corynoline protects against renal IR injury by suppressing oxidative stress, inflammatory responses, and apoptosis, and its mechanism of action may involve the activation of the Nrf2/HO-1 pathway.
Insights
Corynoline effectively treats kidney injury from ischemia-reperfusion (IR) by reducing oxidative stress and inflammation. Its protective mechanism involves activating the Nrf2/HO-1 pathway, offering a potential therapeutic strategy for kidney diseases.
Area of Science:
- Nephrology
- Pharmacology
- Molecular Biology
Background:
- Oxidative stress and inflammation are key contributors to various diseases.
- Corynoline's therapeutic potential is recognized, but its role in renal ischemia-reperfusion (IR) injury is not well-defined.
Purpose of the Study:
- To investigate the protective effects of corynoline on renal IR injury.
- To elucidate the underlying mechanism of corynoline's action in renal IR injury.
Main Methods:
- A rat model of renal IR injury was established.
- Kidney tissue and blood samples were analyzed for damage, inflammation, oxidative stress, and apoptosis.
- The expression of Nrf2 (nuclear factor erythroid 2-related factor 2) and HO-1 (heme oxygenase-1) was assessed, along with the impact of an Nrf2 inhibitor (ML-385).
Main Results:
- Corynoline significantly ameliorated renal IR injury, improving renal function and reducing tissue damage and apoptosis.
- It suppressed oxidative stress by increasing superoxide dismutase (SOD) and decreasing malondialdehyde (MDA).
- Corynoline inhibited inflammatory responses by reducing neutrophil infiltration and pro-inflammatory cytokine release, and it restored Nrf2/HO-1 expression, with its protective effects being reversed by ML-385.
Conclusions:
- Corynoline exerts protective effects against renal IR injury by mitigating oxidative stress, inflammation, and apoptosis.
- The mechanism of action is linked to the activation of the Nrf2/HO-1 signaling pathway.
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