Korean J Physiol Pharmacol.  2009 Jun;13(3):181-187. 10.4196/kjpp.2009.13.3.181.

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

• Park YY

• KMID: 2071669
• DOI: http://doi.org/10.4196/kjpp.2009.13.3.181

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.

Keyword

Ferritin; Heme oxygenase-1; Ischemia/reperfusion; Acute lung injury; ARDS

MeSH Terms

Acute Lung Injury
Animals
Bronchoalveolar Lavage
Ferritins
Heme
Heme Oxygenase-1
Humans
Imidazoles
Leukocyte Count
Lung
Lung Injury
Nitro Compounds
Oxidative Stress
Quinacrine
Rats
Respiratory Distress Syndrome, Adult
Salicylamides
Ferritins
Heme
Heme Oxygenase-1
Imidazoles
Nitro Compounds
Quinacrine
Salicylamides

Figure

• 

  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.

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  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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