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Background: Ischemia-reperfusion (I/R) of remote organs is a common cause of lung injury. We observed that lung injury after partial hepatic I/R in mice coincides with the appearance of 3-nitrotyrosine (NT) in the lung tissue, a marker of peroxynitrite involvement and oxidant stress. Peroxynitrite can cause mitochondrial dysfunction by inactivation of manganese superoxide dismutase (MnSOD), the major antioxidant enzyme in mitochondria. Our aims were to examine whether pulmonary MnSOD is a target of nitration following hepatic I/R and whether nitrated MnSOD (N-MnSOD) correlates with acute lung injury.
Methods: Five 20-25-g male C57BL/6 mice underwent laparotomy, and atraumatic occlusion of the portal and arterial blood supply to the upper three lobes of the liver for 90 min. This warm ischemic period was followed by 4 h of reperfusion, and the animals were then euthanized. Lung injury was assessed by LDH and protein levels in bronchoalveolar lavage (BAL) fluid. Pulmonary MnSOD activity in pulmonary homogenates was measured by the cytochrome c reduction method. The presence of N-MnSOD was determined by immunoprecipitation (IP) and Western Blot analysis. Controls (N = 5) underwent sham operation.
Results: Elevated plasma transaminases confirmed hepatic injury. Lung injury was demonstrated by elevation in BAL protein and LDH levels (495.7 (48.4) versus 644.9 (37.3) [p < 0.05] and 56.5 (11.8) versus 345.2 (80) [p < 0.01], respectively). Immunoprecipitation and Western blot demonstrated N-MnSOD in the lung tissue of I/R animals but not controls. MnSOD activity decreased following I/R (8.1 (0.7) versus 10.8 (0.3) [p < 0.05]).
Conclusions: Pulmonary MnSOD is both nitrated and inactivated following hepatic I/R and is associated with acute lung injury. These findings suggest that MnSOD incapacitance may contribute to I/R-induced lung injury and provide a therapeutic target in attenuating multisystem injury following hepatic I/R.
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http://dx.doi.org/10.1089/sur.2004.5.166 | DOI Listing |
Cent Eur J Immunol
November 2024
Department of Emergency, People's Hospital of Ningxiang City, Ningxiang, Hunan, China.
Introduction: Neonatal sepsis (NS) seriously threatens the health of infants. Coactosin-like protein 1 (COTL1) is a binding protein of F-actin and 5-lipoxygenase which is known to regulate the progression of neonatal sepsis. Nevertheless, the function of COTL1 in NS is not clear.
View Article and Find Full Text PDFRespir Res
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Department of Anesthesiology, Guangxi Medical University Cancer Hospital, He Di Rd No.71, Nanning, 530021, P. R. China.
Mechanical ventilation (MV) remains a cornerstone of critical care; however, its prolonged application can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). Although previous studies have implicated ferroptosis in the pathogenesis of VILI, the underlying mechanisms remain unclear. This study investigated the roles of ferritinophagy in ferroptosis subsequent to VILI.
View Article and Find Full Text PDFFood Chem Toxicol
December 2024
State Key Laboratory of Cellular Stress Biology, Department of Thoracic Surgery in Xiang'an Hospital of Xiamen University, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China. Electronic address:
Black phosphorus nanomaterials (BPNM) exhibit excellent properties and potential applications in electronics, but workers may face inhalation exposure during BPNM production. In addition, there is a lack of biosafety assessments regarding respiratory exposure to BPNM of different sizes. In this study, we investigated the lung toxicity in mice exposed to 5, 50, 500 μg/kg of black phosphorus quantum dots (BPQDs) and black phosphorus nanosheet (BPNS) via single tracheal instillation.
View Article and Find Full Text PDFLancet Child Adolesc Health
December 2024
Department of Pediatrics, University of Ottawa and Children's Hospital of Eastern Ontario and Children's Hospital of Eastern Ontario Research Institute, Ottawa, ON, Canada.
Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.
View Article and Find Full Text PDFInflammation
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Zhejiang Provincial Key Laboratory of Interventional Pulmonology, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
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