Oxidative stress and nitric oxide deficiency in inflammation of chronic renal failure. Possible preventive role of L-arginine and multiple antioxidants

OBJECTIVE: To evaluate the effect of L-arginine and multiple antioxidants on the inflammatory cytokines level, renal functions, blood pressure and dyslipidemia in chronic renal failure (CRF) rats.

METHODS: This study was carried out between December 2007 and November 2008 in the Department of Physiology, Faculty of Medicine, King Saud University, Kingdom of Saudi Arabia. Chronic renal failure was induced in 40 rats by renal mass reduction (RMR) and 10 rats were sham operated. Renal mass reduction rats were treated for 12 weeks by L-arginine and/or a mixture of antioxidants (L-carnitine, Catechin, Vitamins E and C) and the effect of the treatments on plasma cytokines, soluble intercellular adhesion molecule-1 (sICAM-1), nitrate (NO2) and nitrites (NO3), lipid profile, blood pressure, and renal function was examined.

RESULTS: Chronic renal failure increased plasma Interleukin (IL)-1alpha, IL-1beta, IL-6, tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1 (sICAM-1) levels and decreased anti-inflammatory cytokines IL-4 and 10 levels. In addition, hypertension, and dyslipidemia were found. L-arginine treatment improved kidney functions, decreased systolic blood pressure and decreased inflammatory cytokines levels. Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels and increased IL-4 levels. Combined use of L-arginine and the antioxidants mixture were very effective in their tendency to recover normal values of kidney functions, plasma cytokines, sICAM-1, blood pressure, NO2/NO3, cholesterol and triglycerides concentrations.

CONCLUSION: Restoration of the pro-oxidant/ antioxidants balance with increased NO bio-availability counteracts inflammation, renal impairment and dyslipidemia in CRF. This may open new perspectives for the role of antioxidants and NO precursors in the treatment of uremia and its complications.