Curcumin Attenuates Hemorrhagic Shock and Blood Replenish Resuscitation-induced Impairment of Pulmonary Barrier Function by Increasing SIRT1 and Reducing Malondialdehyde and TNF-α Contents and Neutrophil Infiltration in Lung in a Dose-Dependent Fashion.

OBJECTIVES

Acute lung injury (ALI) is a critical complication subsequent to hemorrhage shock and resuscitation (HSR) that frequently leads to multiple organ failure. Collective evidence suggested that the activation of pulmonary nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1) plays a critical role in inhibiting the production of reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α, as well as the protection against ALI. Curcumin is a potent activator of SIRT1 and possesses antioxidative and anti-inflammatory effects. In this study, we aim to investigate the dose-dependent protective effectiveness of curcumin pretreatment against HSR-induced ALI.

METHODS

Studies were conducted on Sprague-Dawley male rats in 5 groups: sham-operated, HSR, and HSR pretreated with 50, 200, or 400 mg/kg of curcumin. Curcumin was treated orally for 4 days and 1 hour before HSR induction. HSR was induced by decreasing the mean aortic pressure (MAP) to 40 mm Hg for 60 min through drawing blood from the left femoral artery, followed by blood replenish and leaving for another 120 min. At the end of HSR, the severity of ALI was assessed by pulmonary barrier function, via pulmonary filtration coefficient (K) evaluated using isolated a perfused lung model, lung weight-to-body weight ratio (LW/BW), lung wet-to-dry weight ratio (W/D), and lavage protein concentration (PCBAL). We also examined the level of lung inflammation by lavage TNF-α and differential neutrophil count, and oxidative stress by lavage malondialdehyde (MDA).

RESULTS

HSR significantly increased K, LW/BW, W/D, and PCBAL; decreased pulmonary SIRT1; and increased lavage TNF-α and MDA contents and differential neutrophil count (P < .05). Curcumin pretreatment demonstrated lung protection efficacy with improved pulmonary barrier function, increased lung SIRT1, and reduced pulmonary oxidative stress and lung inflammation in a dose-dependent fashion.

CONCLUSIONS

Curcumin pretreatment protects against HSR-induced pulmonary function impairment by increasing tissue SIRT1, which reduced lavage MDA and TNF-α and differential neutrophil count in a dose-dependent fashion.