Objective: To explore the mechanism of Aspirin induced ferritin synthesis on resistance to oxidative damage in endothelial cells.
Methods: Using cultured endothelial cells, we measured the effect of aspirin with different incubative time (4 - 24 h) and different concentration (0.1 - 3 mmol/L), salicylic acid and indomethacin induced ferritin expression by ELISA kit, and observed the change of lactate dehydrogenase (LDH) release rate, malondialdehyde (MDA) and cellular viability after preincubating the cell for 8 h with aspirin on resistance to hydrogen peroxide toxicity. Statistical analysis using a one-way analysis of variance.
Results: Aspirin at low concentration (0.1 mmol/L) induced significant increase ferritin expression in a concentration-dependent fashion: (5.8 +/- 0.3) ng/10(6) cell (0.1 mmol/L As), (6.4 +/- 0.4) ng/10(6) cell (0.5 mmol/L As), (7.0 +/- 0.7) ng/10(6) cell (1 mmol/L As), (7.4 +/- 0.4) ng/10(6) cell (2 mmol/L As), (7.7 +/- 0.5) ng/10(6) cell (3 mmol/L As), significant for all values: P < 0.05 versus normal control. Induction of ferritin levels by aspirin (1 mmol/L) was also time dependent: (5.8 +/- 1.0) ng/10(6) cell (4 h, but P > 0.05 vs control), (6.5 +/- 1.0) ng/10(6) cell (8 h, P < 0.05 vs control) and (7.8 +/- 0.8) ng/10(6) cell (24 h). Preincubating the cells with aspirin (0.1 mmol/L) reduced LDH release rate by 50%, toxicity reduction by 40%, and significant decrease MDA production. Aspirin induced cytoprotection from H(2)O(2) damage was also in a concentration dependent fashion. The cytoprotection of aspirin was mimicked by exogenous iron-free apo-ferritin but not iron-load ferritin. Salicylic acid and indomethacin failed to increase ferritin expression.
Conclusion: Aspirin could induce significant increase ferritin synthesis at low concentration (0.1 mmol/L). Ferritin induction by aspirin was specific in nonsteroidal anti-inflammatory drugs.