Anti-inflammatory effect of thalidomide in an experimental lung donor model of brain death

Abstract

Lung transplantation stands as a vital treatment for severe lung diseases, primarily sourcing organs from donors with brain death (BD). This research delved into the potential anti-inflammatory effects of thalidomide in rats with BD-induced lung complications. In this study twenty-four Wistar rats were divided into three groups: the control (CTR), brain death (BD) and brain death + thalidomide (TLD) groups. Post specific procedures, a 360 min monitoring period ensued. Comprehensive analyses of blood and heart-lung samples were conducted. Elevated IL-6 levels characterized both BD and TLD groups relative to the CTR (p = 0.0067 and p = 0.0137). Furthermore, TNF-α levels were notably higher in the BD group than both CTR and TLD (p = 0.0152 and p = 0.0495). Additionally, IL-1β concentrations were significantly pronounced in both BD and TLD compared to CTR, with the BD group surpassing TLD (p = 0.0256). Immunohistochemical assessments revealed augmented NF-ĸB expression in the BD group in comparison to both CTR and TLD (p = 0.0006 and p = 0.0005). With this study we can conclude that BD induced acute pulmonary inflammation, whereas thalidomide manifested a notable capability in diminishing key inflammatory markers, indicating its prospective therapeutic significance in lung transplantation scenarios.

Figure 1

MAP monitoring in the TLD and BD groups during the 360 min of the experiment. Values are expressed as the mean ± standard error of the mean, and a p value < 0.05 was considered to indicate statistical significance. Two-way ANOVA followed by Sidak’s post hoc test. TTO, treatment. *p = 0.0098.

Figure 2

Analysis of the wet/dry weight ratio Values are expressed as the mean ± standard error of the mean, and groups were tested using analysis of variance (one-way ANOVA) with Tukey’s post hoc test. A p value of < 0.05 was considered to indicate statistical significance. ^#p = 0.0083; *p = 0.0092.

Figure 3

Analysis of IL-6 (a), TNF-α (b), and IL-1β (c) levels and myeloperoxidase activity (d) in lung homogenates. Values are expressed as the mean ± standard error of the mean, and groups were tested using analysis of variance (one-way ANOVA) with Tukey’s post hoc test (Fig. 3a,b,d) and Student’s t test (Fig. 3c). A p value of < 0.05 was considered to indicate statistical significance.

Figure 4

Analysis of superoxide dismutase (a) and malondialdehyde (b) levels in lung homogenates. Values are expressed as the mean ± standard error of the mean, and groups were tested using analysis of variance (one-way ANOVA) with Tukey’s post hoc test. A p value of < 0.05 was considered to indicate statistical significance.

Figure 5

Evaluation of the level of the marker NF-κB in a lung tissue sample (a) and immunoexpression of the anti-NF-κB (p65) antibody (b). Values are expressed as the mean ± standard error of the mean, and groups were tested using analysis of variance (one-way ANOVA) with Tukey’s post hoc test. A p value of < 0.05 was considered to indicate statistical significance.

Figure 6

Total leukocyte count in lung tissue (a), analysis of the final leukocyte count in blood samples (b) and rat leukocyte count over time in blood samples (c). Values are expressed as the mean ± standard error of the mean, and groups were tested using one-way analysis of variance (ANOVA) with Tukey’s post hoc test (a,b) and two-way ANOVA with Sidak’s post hoc test (c). A p value < 0.05 was considered to indicate statistical significance.

Figure 7

Analysis of neutrophils in blood samples over time (a) and neutrophil analysis in blood samples (b). Values are expressed as the means ± standard errors of the means, and the groups were tested using analysis of variance (two-way ANOVA) with Sidak’s post hoc test and (one-way ANOVA) with Tukey’s post hoc test. For both tests, a p value of < 0.05 was considered to indicate statistical significance.