Daxas provides renoprotective effects in ischemia-reperfusion injury by targeting apoptosis, oxidative stress, and inflammation pathways.

BACKGROUND AND AIM

The pathophysiology of renal ischemia-reperfusion injury (IRI) is a multifaceted process involving various pathways, including oxidative stress and inflammatory responses. This study was designed to evaluate the renoprotective effect of Daxas, Roflumilast (RFL), a selective phosphodiesterase 4 (PDE4) inhibitor, in preventing IRI consequences in rats.

METHODS

Fifty-four rats were split up into three groups: the sham group, which did not experience any ischemia; the IRI group, which underwent renal IRI for 45 minutes; and the Daxas-treated group, which received 1.2 mg/kg after IRI. At 2, 5, and 7 days, blood and kidney samples were collected to assess renal histopathology, oxidative stress indicators, apoptosis, inflammatory gene analysis, and kidney function.

RESULTS

The outcomes showed that renal IRI significantly impaired kidney function. Furthermore, in a comparison with the sham group, IRI significantly raised the levels of oxidative stress marker malonaldehyde (MDA) in the kidney while significantly decreasing the activities of glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) at 2, 5, and 7 days (p < 0.05). In comparison to the Sham group, IRI also caused a drop in Bcl2 and Nrf2 and an increase in BAX, MPO, IL-6, and TNF-α at the different time intervals (p < 0.05). At different time points, treatment with Daxas significantly improved all of these metrics when compared to the IRI group (p < 0.05). Immunohistochemical examination of BAX demonstrated a substantial elevation in the IRI group relative to the sham group (p < 0.05), concentrated in tubular epithelial cells and inflammatory infiltrates. Daxas therapy markedly decreased BAX expression to levels akin to the sham group (p < 0.05).

CONCLUSIONS

Daxas demonstrated potent kidney-protective benefits by reducing oxidative stress, enhancing renal function, and modifying inflammatory and apoptotic pathways. According to these results, Daxas may be a viable treatment choice for reducing the consequences of IRI.