Nephroprotective effects of visnagin through modulation of macrophage polarization, oxidative stress, inflammation and apoptosis in renal I/R injury

Objectives The study aimed to investigate the nephroprotective effects of visnagin on renal ischemia-reperfusion (I/R) injury and the role of M1/M2 macrophage polarization in this process. Methods Forty-two adult rats were divided into six groups: Control, Visnagin30 mg/kg, Visnagin60 mg/kg, I/R, I/R + Visnagin30 mg/kg, I/R + Visnagin60 mg/kg (n=7). Bilateral renal ischemia was induced by clamping for 25 min, followed by 2 h of reperfusion. Visnagin or vehicle was administered to the animals intraperitoneally 2 h before reperfusion. At the end of the study, kidney samples were collected for analysis of oxidative stress, inflammatory cytokines, apoptotic protein expression, and M1/M2 macrophage polarization. Results I/R injury increased malondialdehyde (MDA), chemiluminescence (CL), IL-1β, and IL-6 levels while decreasing glutathione (GSH) in renal tissue, indicating enhanced oxidative stress (p<0.001) and inflammation (p<0.05). Histopathological examination showed glomerular atrophy, tubular degeneration, and intertubular hemorrhage. Visnagin treatment at 60 mg/kg significantly reduced MDA, CL, and IL-1β levels, and increased GSH (p<0.05). Immunohistochemically, visnagin decreased Bax (p<0.001), caspase-3 (p<0.01), and TNF-α (p<0.01) expressions elevated by I/R injury. Furthermore, visnagin reversed I/R induced M1/M2 macrophage polarization (CD86↑, CD163↓), decreasing CD86 (p<0.05) and increasing CD163 immunodensity (p<0.05). Conclusions Visnagin treatment (60 mg/kg) exerts promising nephroprotective effects in renal I/R injury by reducing oxidative stress, inflammation, apoptosis, and modulating M1/M2 macrophage polarization.