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Inhibition of nuclear factor-kappa B activation reduces glycerol-induced renal injury
Telma de Jesus Soares1, Roberto S Costa, Ana Paula C Balbi
1Department of Physiology, School of Medicine, University of Sao Paulo at Ribeirao Preto, Ribeirao Preto, Sao Paulo, Brazil.
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-kappa B) system. The aim of this study was to investigate the expression of NF-kappa B 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-kappa B 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. mmunohistochemical 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-kappa B was greater in glycerol-treated rats than in controls (p<0.001). Glycerol-induced histological nd 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-kappa B expression and decreasing lipid peroxidation in the renal cortex.
Insights
Pyrrolidine dithiocarbamate (PDTC) reduces glycerol-induced kidney injury by inhibiting nuclear factor kappa B (NF-kappa B) activation and decreasing oxidative stress. This antioxidant treatment protects against renal damage and fibrosis in rats.
Area of Science:
- Nephrology
- Molecular Biology
- Toxicology
Background:
- Glycerol injection causes acute tubular necrosis and interstitial fibrosis.
- Oxidative stress in glycerol-treated kidneys activates the nuclear factor kappa B (NF-kappa B) pathway.
- Mitogen-activated protein kinases (MAPKs) are also implicated in renal injury.
Purpose of the Study:
- To investigate NF-kappa B and MAPK expression in rat renal cortex after glycerol injection.
- To determine the relationship between NF-kappa B activation and renal structural/functional changes.
- To evaluate the protective effects of pyrrolidine dithiocarbamate (PDTC), an NF-kappa B inhibitor, against glycerol-induced nephrotoxicity.
Main Methods:
- Male Wistar rats received intramuscular injections of glycerol, glycerol plus PDTC, or saline.
- Kidneys were collected at 5 and 30 days post-injection for histological and immunohistochemical analysis.
- Plasma creatinine, fractional electrolyte excretion, urinary malondialdehyde (MDA), and cortical NF-kappa B expression were measured.
Main Results:
- Glycerol injection increased plasma creatinine and electrolyte excretion, which were attenuated by PDTC.
- Increased cortical expression of macrophages and NF-kappa B was observed in glycerol-treated rats.
- PDTC treatment reduced glycerol-induced histological damage and urinary MDA levels, indicating decreased lipid peroxidation.
Conclusions:
- PDTC attenuates glycerol-induced renal injury.
- The protective effect of PDTC is associated with reduced NF-kappa B expression.
- PDTC mitigates renal damage by decreasing oxidative stress and lipid peroxidation in the renal cortex.
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