RESUMEN
AIMS: To investigate the effect of long-term N-acetyl-l-cysteine (NAC) treatment in Wistar rats subjected to renal ischemia and reperfusion (IR) and a chronic highsodium diet (HSD). MAIN METHODS: Adult male Wistar rats received an HSD (8.0% NaCl) or a normalsodium diet (NSD; 1.3% NaCl) and NAC (600â¯mg/L) or normal drinking water starting at 8â¯weeks of age. At 11â¯weeks of age, the rats from both diet and NAC or water treatment groups underwent renal IR or Sham surgery and were followed for 10â¯weeks. The study consisted of six animal groups: NSDâ¯+â¯Shamâ¯+â¯water; NSDâ¯+â¯IRâ¯+â¯water; NSDâ¯+â¯IRâ¯+â¯NAC; HSDâ¯+â¯Shamâ¯+â¯water; HSDâ¯+â¯IRâ¯+â¯water; and HSDâ¯+â¯IRâ¯+â¯NAC. KEY FINDINGS: Tail blood pressure (tBP) increased with IR and NAC treatment in the NSD group but not in the HSD group. The serum creatinine level was higher after NAC treatment in both diet groups, and creatinine clearance was decreased in only the HSDâ¯+â¯IRâ¯+â¯NAC group. Albuminuria increased in the HSDâ¯+â¯IRâ¯+â¯water group and decreased in the HSDâ¯+â¯IRâ¯+â¯NAC group. Kidney mass was increased in the HSDâ¯+â¯IR group and decreased with NAC treatment. Renal fibrosis was prevented with NAC treatment and cardiac fibrosis was decreased with NAC treatment in the HSDâ¯+â¯IR group. SIGNIFICANCE: NAC treatment promoted structural improvements, such as decreased albuminuria and fibrosis, in the kidney and heart. However, NAC could not recover kidney function or blood pressure from the effects of IR associated with an HSD. Therefore, in general, long-term NAC treatment is not effective and is deleterious to recovery of function after kidney injury.