SERUM FERRITIN ELEVATION AND ACUTE LUNG INJURY IN RATS SUBJECTED TO HEMORRHAGE: REDUCTION BY MEPACRINE TREATMENT

Abstract

□ Ferritin regulates iron levels and, for unknown reasons, serum ferritin concentrations are increased in patients at risk for and with acute lung injury (ALI) and multiple organ failure. Uncomplexed iron could exacerbate the toxicity of the increased oxidative stress that occurs in patients with ALI and multiple organ failure and thereby contribute to disease. In the present investigation, the authors found that serum and lung lavage ferritin concentrations increased in hemorrhaged rats that develop ALI as manifested by increased lung inflammation (increased lung lavage leukocyte counts and lung myeloperoxidase activities) and increased lung leak (increased lung lavage protein concentrations). Treatment with mepacrine, a phospholipase A2 inhibitor, attenuated the increases in serum and lung lavage ferritin concentrations, lung inflammation, and lung leak that occur in rats subjected to hemorrhage. The findings show that serum and lung ferritin levels increase and may play a role in the development of acute lung injury caused by hemorrhage.

Keywords:

• inflammation
• iron
• neutrophils
• oxidants
• shock

Notes

This work was supported in part by grants from the NIH (R01 HL45582), the American Lung Association, the Herrick Bequest, and Newborn Hope.

The authors acknowledge the manuscript preparation assistance of Jacqueline Smith Evans and appreciate the kindness of Dr. Steven Aust (Utah State University, Logan, UT) who provided advice and reagents.