Glycine ameliorates lung reperfusion injury after cold preservation in an ex vivo rat lung model.

Abstract

BACKGROUND:

The role of glycine has not been investigated in lung ischemia-reperfusion injury after cold preservation. Furthermore, the role of apoptosis after reperfusion following cold preservation has not been fully understood.

METHODS:

Lewis rats were divided into three groups (n=6 each). In the GLY(-) and GLY(+) groups, isolated lungs were preserved for 15 hr at 4 degrees C after a pulmonary artery (PA) flush using our previously developed preservation solution (ET-K; extracellular-type trehalose containing Kyoto), with or without the addition of glycine (5 mM). In the Fresh group, isolated lungs were reperfused immediately after a PA flush with ET-K. They were reperfused for 60 min with an ex vivo perfusion model. Pulmonary function, oxidative stress, apoptosis, and tumor necrosis factor (TNF)-alpha expression were assessed after reperfusion.

RESULTS:

Shunt fraction and peak inspiratory pressure after reperfusion in the GLY(-) group were significantly higher than those in the GLY(+) and Fresh groups. Oxidative damage and apoptosis in the alveolar epithelial cells of the GLY(-) group, assessed by immunohistochemical staining and quantification of 8-hydroxy-2'-deoxyguanosine and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method, were significantly higher than those of the GLY(+) and Fresh groups. There were correlations among shunt fraction, oxidative damage, and apoptosis. There was no expression of TNF-alpha messenger RNA in all groups evaluated by the reverse transcription-polymerase chain reaction.

CONCLUSIONS:

Glycine attenuates ischemia/reperfusion injury after cold preservation by reducing oxidative damage and suppressing apoptosis independent of TNF-alpha in this model. The suppression of apoptosis might ameliorate lung function after reperfusion.

• Authors: Mitsugu Omasa, Tatsuo Fukuse, Shinya Toyokuni, Yoichi Mizutani, Hiroshi Yoshida, Kazuyuki Ikeyama, Seiki Hasegawa, Hiromi Wada
• Journal: Transplantation (Transplantation) Vol. 75 Issue 5 Pg. 591-8 (Mar 15 2003) ISSN: 0041-1337 [Print] United States
• PMID: 12640295 (Publication Type: Journal Article)

Chemical References

• 8-Hydroxy-2'-Deoxyguanosine
• Deoxyguanosine
• Glycine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Animals
• Apoptosis
• Blood Pressure
• Cryopreservation
• Cytoprotection
• Deoxyguanosine (analogs & derivatives, metabolism)
• Glycine (pharmacology)
• Immunohistochemistry (methods)
• In Situ Nick-End Labeling
• Inhalation
• Ischemia (physiopathology)
• Lung (metabolism)
• Male
• Oxidative Stress
• Pressure
• Pulmonary Artery (physiopathology)
• Pulmonary Circulation
• Rats
• Rats, Inbred Lew
• Reperfusion Injury (physiopathology)
• Staining and Labeling