Abstract
Ischemia-reperfusion injury (IRI) is one of the factors limiting the success of lung transplantation (LTx). IRI increases death risk after transplantation through innate immune system activation and inflammation induction. Some studies have shown that creatine (Cr) protects tissues from ischemic damage by its antioxidant action. We evaluated the effects of Cr supplementation on IRI after unilateral LTx in rats. Sixty-four rats were divided into four groups: water + 90 min of ischemia; Cr + 90 min of ischemia; water + 180 min of ischemia; and Cr + 180 min of ischemia. Donor animals received oral Cr supplementation (0.5 g/kg/day) or vehicle (water) for five days prior to LTx. The left lung was exposed to cold ischemia for 90 or 180 min, followed by reperfusion for 2 h. We evaluated the ventilatory mechanics and inflammatory responses of the graft. Cr-treated animals showed a significant decrease in exhaled nitric oxide levels and inflammatory cells in blood, bronchoalveolar lavage fluid and lung tissue. Moreover, edema, cell proliferation and apoptosis in lung parenchyma were reduced in Cr groups. Finally, TLR-4, IL-6 and CINC-1 levels were lower in Cr-treated animals. We concluded that Cr caused a significant decrease in the majority of inflammation parameters evaluated and had a protective effect on the IRI after LTx in rats.
Highlights
Lung transplantation (LTx) is a well-established therapeutic option for the treatment of several diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis, bronchiectasis, and primary pulmonary hypertension [1,2,3]
Nutrients 2020, 12, 2765 of LTx is limited by high rates of primary graft dysfunction (PGD) due to ischemia-reperfusion injury (IRI), which is characterized by inflammation, alveolar damage, and vascular permeability [4]
Antioxidant agents have been tested in different experimental models [5,6] including creatine [7,8]
Summary
Lung transplantation (LTx) is a well-established therapeutic option for the treatment of several diseases, such as chronic obstructive pulmonary disease, pulmonary fibrosis, bronchiectasis, and primary pulmonary hypertension [1,2,3]. Other causes include multiple organ and cardiovascular failure and technical failures related to the transplant procedures, as well as bronchiolitis obliterans syndrome [3]. Nutrients 2020, 12, 2765 of LTx is limited by high rates of primary graft dysfunction (PGD) due to ischemia-reperfusion injury (IRI), which is characterized by inflammation, alveolar damage, and vascular permeability [4]. In LTx, organ ischemia and subsequent reperfusion are inevitable and generally lead to acute and sterile inflammation after transplantation, which is called IRI. There are no therapeutic agents used clinically to prevent IRI, and treatment strategies are limited to support care [4]. Antioxidant agents have been tested in different experimental models [5,6] including creatine [7,8]
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