The beneficial effects of dose-dependent myricetin application on renal ischemia and reperfusion injury in a rat model

Background: This study was aimed to evaluate the renoprotective effects of Myricetin at two dosages (50 and 100 mg/kg) within an experimental I/R injury model. The analysis focused on key immunological and oxidative stress pathways, including the regulation of pro- and anti-inflammatory cytokines, NF-κB and TLR4 signaling, as well as biomarkers of oxidative stress such as nitrate (NO), malondialdehyde (MDA), glutathione (GSH), nuclear factor (erythroid-derived 2)-like 2 (NRF2) and Heme oxygenase-1 (HO-1).

Methods and results: Thirty female Wistar albino rats were randomly assigned to six groups. Myricetin was administered via intragastric gavage for seven days before ischemia/reperfusion. Renal ischemia was induced by clamping the left renal pedicle for 45 min, followed by a 3-hour reperfusion period. Kidney tissues were collected for histopathological, immunohistochemical, and biochemical analyses. Serum cytokine levels were measured by ELISA, while protein expressions were evaluated by Western blotting. I/R injury significantly increased pro-inflammatory cytokines and oxidative stress markers, alongside heightened NF-κB immunopositivity and TNF-α, IL-1β expression. Myricetin administration reduced pro-inflammatory cytokines, increased anti-inflammatory cytokines, and enhanced antioxidant responses. Immunohistochemical and Western blot analyses showed decreased NF-κB positivity and increased NRF2 expression.

Conclusions: The renoprotective effects of Myricetin appear to be mediated by inhibiting the NF-κB pathway, reducing inflammation, and enhancing antioxidant responses. Furthermore, Myricetin activates the NRF2/HO-1 pathway, suggesting its potential as a therapeutic agent for ischemia/reperfusion-induced kidney injury.

Apoptosis; Cytokines; Myricetin; Oxidative stress; Renal ischemia/Reperfusion.