Niacin Pretreatment Attenuates Lung Ischemia and Reperfusion-Induced Pulmonary Barrier Function Impairment by Reducing Oxidative Stress and Activating SIRT1 in an Isolated-Perfused Rat Lung Model.
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OBJECTIVE
Alveolar-capillary barrier dysfunction, characterized by alveolar protein leak and lung edema, is a common scenario following cardiopulmonary surgery and thoracic organ transplantation. Reactive oxygen species generated through lung ischemia and reperfusion (I/R) injury during surgery plays a crucial role. Niacin, also known as vitamin B3, has been demonstrated to possess antioxidative and anti-inflammatory capacity. In this study, we examine the pulmonary barrier function via capillary filtration coefficient (Kfc) following lung I/R injury with and without niacin treatment.
METHODS
Studies were conducted on male Sprague-Dawley rats in 3 groups: sham-operated, lung I/R injury, and niacin-pretreated lung I/R injury group. Rats were subjected to isolated perfused lung preparation. Lung ischemia was established by continuous perfusion and stopping ventilation for 60 minutes, followed by 60 minutes of ventilation. We assessed the Kfc, lung water content, and protein concentration in the lung lavage; pulmonary oxidative stress and lung inflammation were assessed by leukocyte counts, tissue level of tumor nercrosis factor alpha (TNF-α), and tissue content of malondialdehyde (MDA), respectively. We also assessed the tissue protein level of sirtuin (silent mating type information regulation 2 homolog) 1 (SIRT1).
RESULTS
Lungs subjected to I/R injury significantly increased Kfc, pulmonary oxidative stress, lung water content, and lavage leukocyte count and protein concentration (P < .05). Rats treated with niacin of 100 mg/kg/day for 4 days increased lung SIRT1 (P < .05) and attenuated lung I/R injury-induced pulmonary oxidative stress and inflammation and also improved Kfc.
CONCLUSIONS
Niacin pretreatment protects lungs against I/R injury-induced barrier function impairment through the activation of SIRT1 and reduced pulmonary oxidative stress and lung inflammation.
