Tuberc Respir Dis.  2011 Jun;70(6):482-489.

Effect of Apocynin on Acute Lung Injury in Rats Given Interleukin-1alpha Intratracheally

• Lee YM

Abstract

BACKGROUND
Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-1alpha (IL-1)-induced ALI in rats.
METHODS
IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (gamma-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated.
RESULTS
Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin.
CONCLUSION
Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

Keyword

apocynin; NADPH Oxidase; Acute Lung Injury; Neutrophils

MeSH Terms

Acetophenones
Acute Lung Injury
Animals
Bronchoalveolar Lavage
Cytosol
Free Radicals
Humans
Interleukin-1
Interleukin-1alpha
Lung
Lung Injury
Myristic Acid
NADPH Oxidase
Neutrophils
Oxidative Stress
Phorbols
Phospholipases A2
Rats
Rats, Sprague-Dawley
Superoxides
Trachea
Acetophenones
Free Radicals
Interleukin-1
Interleukin-1alpha
Myristic Acid
NADPH Oxidase
Phorbols
Phospholipases A2
Superoxides

Figure

• 

  Figure 1 Effect of apocynin on ultrastructure of alveolar type II cell in the lung of rat given IL-1 intratracheally. In the alveolar type II cell of sham treated rat, well-preserved lamellar bodies were visible (A, original magnification, ×6,000). By contrast, alveolar type II cell in IL-1 given rat showed large vacuoles which had been lamellar bodies (*). This finding is a pathognomonic sign of pulmonary oxidative stress (B, original magnification, ×10,000). Apocynin did not alter the ultrastructural changes by the IL-1-induced oxidative stress (C, original magnification, ×10,000). LB: lamellar body; M: mitochondria; AT-II: alveolar type II cell; Np: neutrophil.

• 

  Figure 2 Effect of apocynin on the expression of cPLA2 in the cells in BAL. The cells in BAL from sham treated rats did not show the expression of cPLA2, and the majority of the cells were monocytes (A, propidium iodide, original magnification, ×200). By contrast, in BAL of IL-1 treated rats, almost all of the cells were neutrophils and the expression of cPLA2 was conspicuous in their cytoplasm (B, propidium iodide, original magnification, ×100). On the other hand, apocynin did not suppress the expression of cPLA2 of the cells in BAL of IL-1 treated rats (C, propidium iodide, original magnification, ×200).

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