Elsevier

Transplantation Proceedings

Volume 52, Issue 6, July–August 2020, Pages 1875-1879
Transplantation Proceedings

16th Congress of the Asian Society of Transplantation
Experimental studies
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

https://doi.org/10.1016/j.transproceed.2020.01.133Get rights and content

Highlights

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    Hemorrhagic shock and resuscitation (HSR)-impaired pulmonary barrier function, decreased pulmonary SIRT1, and increased pulmonary oxidative stress and inflammation.

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    In a dose-dependent fashion, curcumin pretreatment increased SIRT1, decreased oxidative stress and inflammation in the lungs, and protected pulmonary barrier function against HSR.

Abstract

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 (Kfc) 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 Kfc, 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.

Section snippets

Experimental Design

The study was performed on male Sprague-Dawley rats, weighted 250 to 300 g (Biolasco Co, Taipei, Taiwan) in 5 groups: sham-operated (sham; n=6), HSR (n=6), and HSR pretreated orally with 50, 200, and 400 mg/kg of curcumin (HSR+C50, HSR+C200, HSR+C400, n=6 each) 4 days and 1 hour before the induction of HSR. The doses of 50, 200, and 400 mg/kg of oral curcumin treatment had previously been utilized in studies of indomethacin-induced small intestinal damage in rats by Menozzi et al [10], in

Data Analysis

Data were presented as mean ± SD. Comparisons across multiple groups were analyzed using one-way analysis of variance with a Tukey post hoc test. P < .05 was considered statistically significant.

Results

As shown in Fig 1, hemorrhagic shock and resuscitation (HSR)-induced pulmonary barrier function impairment was evident by markedly increased Kfc (Fig 1A), lung W/D weight ratio (Fig 1B), lung LW/BW ratio (Fig 1C), and protein concentration in the bronchoalveolar lavage fluid PCBAL (Fig 1D); increased pulmonary oxidative stress with increased lavage malondialdehyde (Fig 1E); elevated lung inflammation with increased lavage TNF-α (Fig 1F) and neutrophil differential count (Fig 1G); and

Discussion

In the current study, we demonstrated that HSR induced a marked decrease in pulmonary SIRT1 content, as well as impaired pulmonary barrier function with significantly increased Kfc, lung water content, and protein leak, along with notably increased pulmonary oxidative stress and lung inflammation. Curcumin pretreatment attenuated HSR-induced ALI in a dose-dependent fashion: 50 mg/kg/day of curcumin comprehensively restored pulmonary SIRT1 content and reduced pulmonary oxidative stress and lung

References (20)

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Sources of Funding: Operating grants (107-SKH-FJU-06) from the Shin Kong Wu Ho-Su Memorial Hospital, Taiwan.

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