Inhibition of nuclear factor-κB activation reduces glycerol-induced renal injury

Background: Glycerol injection induces acute tubular necrosis that can progress to interstitial fibrosis. The oxidative stress seen in glycerol-treated animals can activate the nuclear factor kappa B (NF-κB) system. The aim of this study was to investigate the expression of NF-κB and mitogen-activated protein kinases (MAPKs) in the renal cortex and to determine its relationship with structural and functional renal changes in rats treated with glycerol or glycerol plus pyrrolidine dithiocarbamate (PDTC), a nonspecific NF-κB inhibitor with antioxidant properties. Methods: Male Wistar rats were injected intramuscularly with 8 ml/kg of either 50% glycerol (n=22), glycerol + PDTC (n=25) or 0.15 M saline (n=10). The rats were killed, and the kidneys removed at 5 or 30 days after injection. Immunohistochemical results were scored according to the extent of staining. Interstitial lesions were evaluated through morphometry. Lipid peroxidation was estimated by measuring malondialdehyde in urine samples from control rats and glycerol-injected rats. Results: By postinjection day 5, glycerol-only treated rats presented transitory increases in plasma creatinine levels, as well as in fractional excretion of sodium and potassium (p<0.001), which were attenuated in glycerol + PDTC treated rats (p<0.05). Cortical expression of macrophages and NF-κB was greater in glycerol-treated rats than in controls (p<0.001). Glycerol-induced histological and immunohistochemical changes were attenuated by the addition of PDTC (p<0.001), which also reduced the glycerol-induced increase in urinary malondialdehyde (MDA) levels (p<0.05). Conclusions: We conclude that PDTC attenuates glycerol-induced renal injury by reducing NF-κB expression and decreasing lipid peroxidation in the renal cortex.