Apigenin Reduces NF-κB and Subsequent Cytokine Production as Protective Effect in a Rodent Animal Model of Lung Ischemia-Reperfusion Injury.
OBJECTIVE
Lung ischemia-reperfusion injury (LIRI) can complicate lung transplantation or cardiac surgery with cardiopulmonary bypass, increasing morbidity and mortality. In LIRI, pro-inflammatory cytokines are activated, reactive oxygen species are generated and nuclear factor-κB (NF-κB) is up-regulated, altering lung mechanics. We tested the effect of the flavonoid apigenin on a rodent model of LIRI.


METHODS
Thirty-seven Wistar rats were subjected to LIRI with or without a single or double dose of apigenin. Induction of LIRI involved sternotomy and clamping of either the left lung hilum or the pulmonary artery alone for 30 min, followed by 60 min of reperfusion. Control groups consisted of LIRI plus NaCl, a sham group and a baseline group. At the end of the experiments, both lungs were analyzed by RT-PCR, Western blot, and light microscopy.


RESULTS
In placebos, the expression levels of pro-inflammatory markers were increased in both lungs significantly, whereas NF-κB was markedly up-regulated. Administration of apigenin reduced the activation of NF-κB and the expression of TNFα, iNOS, and IL-6. These effects were observed in total lung ischemia. Histology showed greater hemorrhage and exudation in the pulmonary periphery of all groups, whereby damage was practically absent in the central lung regions of the apigenin animals. A second dose of apigenin did not outclass a single one.


CONCLUSIONS
We conclude that apigenin given intraperitoneally can reduce activation of NF-κB and also attenuate the expression of TNFα, IL-6, and iNOS in a surgical model of LIRI. The surgical procedure itself can induce significant damage to the lungs.
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Ioannis
http://orcid.org/0000-0002-2267-8184
I
Bougioukas
b Department of Cardiothoracic Surgery , University of Thrace , Alexandroupolis , Greece.
Vassilios
V
Didilis
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Alexander
A
Emmert
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Ahmad F
AF
Jebran
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Regina
R
Waldmann-Beushausen
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Tomislav
T
Stojanovic
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Friedrich A
FA
Schoendube
a Department of Thoracic and Cardiovascular Surgery , University Medical Center , Göttingen , Germany.
Bernhard C
BC
Danner
D000818:Animals; D047310:Apigenin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000473:pathology / Q000601:surgery; D055370:Lung Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015854:Up-Regulation
D018836:Inflammation Mediators; D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D047310:Apigenin
NF-κB, TNFα; apigenin; interleukins; lung ischemia-reperfusion injury