Ischemia/reperfusion Lung Injury Increases Serum Ferritin and Heme Oxygenase-1 in Rats

Yoon-Yub Park

doi:10.4196/kjpp.2009.13.3.181

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Park: Ischemia/reperfusion Lung Injury Increases Serum Ferritin and Heme Oxygenase-1 in Rats

Original Article

Korean J Physiol Pharmacol 2009;13(3):181-187.

Published online: 17 June 2009

DOI: https://doi.org/10.4196/kjpp.2009.13.3.181

Ischemia/reperfusion Lung Injury Increases Serum Ferritin and Heme Oxygenase-1 in Rats

Yoon-Yub Park

Department of Physiology, School of Medicine, Catholic University of Daegu, Daegu 705-718, Korea

Corresponding to: Yoon-Yub Park, Department of Physiology, School of Medicine, Catholic University of Daegu, 3056-6, Daemyeong-dong, Nam-gu, Daegu 705-718, Korea. (Tel) 82-53-650-4475, (Fax) 82-53-621-4106, (E-mail) yypark@cu.ac.kr

Received 24 April 200911 May 2009 Accepted 25 May 2009

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Intestinal ischemia/reperfusion (I/R) is one of common causes of acute lung injury (ALI). Early and accurate diagnosis of patients who are like to develop serious acute respiratory distress syndrome (ARDS) would give a therapeutic advantage. Ferritin and heme oxygenase-1 (HO-1) are increased by oxidative stress and are potential candidates as a predictive biomarker of ARDS. However, the mechanisms responsible for the increases of ferritin and HO-1, and their relationship to ALI, are unclear. In order to elucidate the interactions between ferritin and HO-1, we studied the changes in ferritin and HO-1 levels in serum and bronchoalveolar lavage (BAL) fluid after intestinal I/R injury in rats. Leukocyte number and protein contents in BAL fluid were elevated following I/R, and the increases were attenuated by mepacrine pretreatment. Both serum ferritin and HO-1 concentrations were progressively elevated throughout the 3 h observation period. Mepacrine pretreatment attenuated the increase of serum and BAL fluid ferritin concentrations, but did not suppress the increase of serum HO-1. Moreover, BAL fluid HO-1 levels did not change after I/R or after mepacrine pretreated I/R compared with sham rats. Unlike ferritin, HO-1 levels are not exactly matched with the ALI. Therefore, there might be a different mechanism between the changes of ferritin and HO-1 in intestinal I/R-induced ALI model.

Keywords: Ferritin, Heme oxygenase-1, Ischemia/reperfusion, Acute lung injury, ARDS

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Fig. 1.

Intestinal ischemia/reperfusion (I/R) significantly increased the number of leukocytes in lung lavage fluids. Mepacrine pretreatment (Mepa+I/R) effectively suppressed the increase. The data shown are means±S.E.M. for the number of rats shown in the parentheses. ∗p<0.05, ∗∗p<0.01, compared with Sham; ^##p<0.01, compared with I/R.

Fig. 2.

Rats subjected to intestinal ischemia/reperfusion (I/R) had significantly increased protein contents in lung lavage fluids. This change was significantly attenuated by the pretreatment with mepacrine (Mepa+I/R). The data shown are means±S.E.M. for the number of rats shown in the parentheses. ∗∗p<0.01, compared with Sham; ^###p<0.001, compared with I/R.

Fig. 3.

Rats subjected to ischemia/reperfusion (I/R) had greatly increased serum ferritin concentrations after 60 min following I/R. Serum ferritin concentrations of I/R rats at 180 min of reperfusion were significantly higher than those of other rats. By comparison, mepacrine pretreatment (Mepa+I/R) significantly attenuated the increase following I/R. Serum ferritin concentrations of sham rats did not change through the observation period. Each point represents mean±S.E.M. for the number of rats shown in the parentheses. ∗p<0.05, ∗∗∗p<0.001, compared with Sham; ^#p<0.05, ^###p<0.001, compared with Mepa+I/R.

Fig. 4.

Rats subjected to ischemia/reperfusion (I/R) had greatly increased serum heme oxygenase-1 (HO-1) concentrations after 3 hours of reperfusion compared to Sham rats. At 180 min following I/R, HO-1 levels of mepacrine-treated rats (Mepa+I/R) was significantly higher than the values of untreated I/R and sham rats. Serum HO-1concentrations of sham rats did not change over the course of the experiment. Each point represents mean±S.E.M. for the number of rats shown in the parentheses. ∗∗∗p<0.001, compared with Sham; ^#p<0.05, compared with Mepa+I/R.

Fig. 5.

Intestinal ischemia/reperfusion (I/R) significantly increased lung lavage fluid ferritin concentrations. Mepacrine pretreatment (Mepa+I/R) significantly reduced the increase. The data shown are means±S.E.M. for the number of determinations shown in the parentheses. ∗∗∗p<0.001, compared with Sham; ^##p<0.01, compared with I/R.

Fig. 6.

There were no significant differences in lung lavage heme oxygenase-1 (HO-1) concentrations among all groups. Ischemia/reperfusion (I/R) did not change HO-1 levels compared to the values of sham rats. The data shown are means±S.E.M. for the number of rats shown in the parentheses.

Fig. 7.

Intestinal ischemia/reperfusion (I/R) significantly increased lung tissue ferritin content. Mepacrine pretreatment (Mepa+I/R) slightly reduced the increase. The data shown are means±S.E.M. for the number of determinations shown in the parentheses. ∗p<0.05, compared with Sham.

Fig. 8.

Intestinal ischemia/reperfusion (I/R) had tendency to increase intestinal tissue ferritin contents. Mepacrine pretreatment (Mepa+ I/R) attenuated the tendency. The data shown are means±S.E.M. for the number of rats shown in the parentheses.

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