N-acetyl cysteine in combination with forelimbs remote ischemic preconditioning improves the contrast-induced nephropathy: an in-vivoexperimental study

Introduction: Given some limitations in the efficacy of N-acetyl cysteine (NAC) or remote ischemic preconditioning (RIPC) to prevent contrast-induced nephropathy (CIN), the present study investigated the beneficial effects of NAC alone or in combination with RIPC on CIN prevention. Methods: Rats were randomly assigned into five groups of eight animals each. Group 1 was sham-operated controls. In group 2, an experimental model of diatrizoate-induced CIN was induced. In groups 3 and 4, NAC (150 mg/kg orally, 24 h before the CIN induction) or RIPC (3 cycles of 4 min/4 min of ischemia and reperfusion in the forelimbs 24 h before the CIN induction) was applied, and both strategies were applied in group 5. 48 hours after the intervention, serum was collected to assess creatinine (Cr) and blood urea nitrogen (BUN) levels. Kidney tissue samples were also kept to evaluate the histology and measure malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity. Results: Considerable increases in serum Cr (0.82±0.04 vs 0.53±0.03 mg/dl) and BUN (49.87±2.85 vs 22.93±1.11 mg/dl) levels in the CIN group showed renal functional damages compared to the sham group. The morphological changes (2 vs 0 score), increased renal MDA levels (8.11±1.27 vs 3.12±0.52 μmol/100 mg tissue), and decreased renal SOD activity (2.29±0.65 vs 27.32±0.98 U/g tissue) in the CIN group represent a remarkable renal injury and oxidative stress compared to the sham group. The individual use of NAC (serum Cr levels: 0.59±0.01 mg/dl; serum BUN levels: 27.24±1.01 mg/dl; morphological changes: 1 score; renal MDA levels: 4.35±0.58 μmol/100 mg tissue; renal SOD activity: 17.24±1.48 U/g tissue) and RIPC (serum Cr levels: 0.60±0.03 mg/dl; serum BUN levels: 28.78±1.66 mg/dl; morphological changes: 1 score; renal MDA levels: 5.34±0.53 μmol/100 mg tissue; renal SOD activity: 13.11±1.96 U/g tissue) improved all indices above. However, the combination of NAC and RIPC (serum Cr levels: 0.57±0.01 mg/dl; serum BUN levels: 25.32±1.14 mg/dl; morphological changes: 1 score; renal MDA levels: 3.56±0.52 μmol/100 mg tissue; renal SOD activity: 30.54±2.92 U/g tissue) was more effective than other strategies used alone. Conclusion: The combined use of NAC and RIPC may be more useful in preventing CIN than the individual use of possible additive effects through reducing oxidative stress.