Effects of cyclosporin A pre-treatment combined with etomidate post-treatment on lung injury induced by limb ischemia-reperfusion in rats

Zou, Haibo; Sun, Xiaofang

doi:10.1177/0300060520934627

Cited by 5 publications

(4 citation statements)

References 25 publications

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“…Our previous studies indicated curcumin post-conditioning could play a protective role in the lung injuries induced by limb I/R via inhibiting the TRL4/NF-κB p65 pathway. 11 Our previous research results also showed similar protective effects in the rat kidney, as assessed using the matrix metalloproteinase (MMP)-9/ tissue inhibitors of metalloproteinase (TIMP)-1 ratio during the process of limb I/R, 12 but the protective effects in the rat lung via the Notch2/Hes-1 signal pathway were not reported. In our experiment, inflammatory cell infiltration, alveolar septum thickening, alveolar interstitial congestion and edema, and occasional localized atelectasis were observed in the lung HE pathology section in the I/R group.…”

Section: Discussionmentioning

confidence: 77%

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Feng

2019

J Int Med Res

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Objective To investigate the influence of curcumin on the Notch2/Hes-1 pathway after pulmonary injury induction via limb ischemia–reperfusion (I/R). Methods Adult male Sprague–Dawley rats were randomly divided into four groups (n = 30 each): sham, I/R, curcumin post-treatment (I/R+Cur), and inhibitor (I/R+DAPT). Hind-limb ischemia was induced for 4 hours, followed by reperfusion for 4 hours. After ischemia, curcumin (200 mg/kg) or DAPT (0.5 µm) was injected intraperitoneally in the I/R+Cur or I/R+DAPT group, respectively. PaO2 was examined after 4 hours of reperfusion. Pathological changes in the lung and the apoptotic index (AI) were examined. Lung malondialdehyde (MDA), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β levels, the wet/dry (W/D) ratio, semi-quantitative score of lung injury (SSLI), and Notch2 protein and Hes-1 mRNA expression were also examined. Results In the I/R group, inflammatory changes were observed, AI increased, and MDA, SSLI, W/D, TNF-α, IL-1β, Notch2, and Hes1-mRNA expression increased, while PaO2 decreased compared with the Sham group. Pathological changes in the I/R+Cur group were reversed. All indexes in the I/R+DAPT and I/R+Cur group were similar. Conclusion Curcumin post-treatment reduced I/R-induced lung injury in rats. Its mechanism may be related to the inhibition of Notch2/Hes-1 signaling pathway and the release of inflammatory factors.

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Section: Discussionmentioning

confidence: 77%

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Feng

2019

J Int Med Res

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“…The pretreatment protocol design is widely used in the field of solid organ transplantation and pathologies involving uncontrolled production of circulating inflammatory cells. Immunosuppressants, such as calcineurin inhibitors, have been used as a pretreatment in several models of ALI (15,16) and in the field of transplantation (29,30). Our experimental protocol evaluating therapeutic intervention with tacrolimus as a pretreatment before brain death is the first step to highlight the potential therapeutic use of tacrolimus in lung allograft preservation in the condition but requires further study in a more clinically translational way after declaration of brain death.…”

Section: Discussionmentioning

confidence: 99%

“…Tacrolimus, a macrolide immunosuppressant belonging to the calcineurin inhibitor family, modulates the cellular immune and nonimmune mechanisms responsible for acute lung graft rejection, such as reduced pulmonary capillary leakage and decreased leukocyte infiltration, as well as the altered release of proinflammatory cytokines (12)(13)(14). Interestingly, calcineurin inhibitors have already been used successfully as a pretreatment in several models of acute lung injury (ALI) (15)(16)(17)(18), but never in brain death-induced lung injury.…”

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confidence: 99%

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death–induced Lung Injury in Pigs

Belhaj

Dewachter

Hupkens

et al. 2022

Am J Respir Crit Care Med

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Rationale: Donor brain death-induced lung injury may compromise graft function after transplantation. Establishing strategies to attenuate lung damage remains a challenge because the underlying mechanisms remain uncertain.Objectives: The effects of tacrolimus pretreatment were evaluated in an experimental model of brain death-induced lung injury.Methods: Brain death was induced by slow intracranial infusion of blood in anesthetized pigs after randomization to tacrolimus (orally administered at 0.25 mg Á kg 21 twice daily the day before the experiment and intravenously at 0.05 mg Á kg 21 1 h before the experiment; n = 8) or placebo (n = 9) pretreatment. Hemodynamic measurements were performed 1, 3, 5, and 7 hours after brain death. After euthanasia of the animals, lung tissue was sampled for pathobiological and histological analysis, including lung injury score (LIS).Measurements and Main Results: Tacrolimus pretreatment prevented increases in pulmonary arterial pressure, pulmonary vascular resistance, and pulmonary capillary pressure and decreases in systemic arterial pressure and thermodilution cardiac output associated with brain death. After brain death, the ratio of Pa O 2 to FI O 2 decreased, which was prevented by tacrolimus. Tacrolimus pretreatment prevented increases in the ratio of IL-6 to IL-10, VCAM1 (vascular cell adhesion molecule 1), circulating concentrations of IL-1b, and glycocalyx-derived molecules. Tacrolimus partially decreased apoptosis (Bax [Bcl2associated X apoptosis regulator]-to-Bcl2 [B-cell lymphoma-2] ratio [P = 0.07] and number of apoptotic cells in the lungs [P , 0.05]) but failed to improve LIS.Conclusions: Immunomodulation through tacrolimus pretreatment prevented pulmonary capillary hypertension as well as the activation of inflammatory and apoptotic processes in the lungs after brain death; however, LIS did not improve.

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“…However, after the ischaemia-reperfusion of tissues and organs, the injury does not stop and it may be further aggravated. 1 Organs with an abundant blood supply can even experience two phases of pathological damage. Research has shown that pulmonary injury induced by limb ischaemia-reperfusion is a complex process involving multiple signalling pathways and factors.…”

Section: Introductionmentioning

confidence: 99%

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway

Zou

Sun

2020

J Int Med Res

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Objective To investigate the mechanism by which curcumin prevents lung injury in a rat model of limb ischaemia-reperfusion injury. Methods Rats were randomized into four groups ( n = 20): control group (sham group); ischaemia-reperfusion group (I/R group); curcumin group (I/R+Cur group); and inhibitor of agomir-21 group (I/R+Cur+antagomir-21 group). At 3 h after reperfusion, lung tissues were collected for histopathology and immunohistochemistry to determine the apoptosis index (AI). Lung injury score (LIS) and lung wet/dry (W/D) ratio were determined. Lung microRNA-21 (miR-21) mRNA levels were measured using reverse transcription–polymerase chain reaction. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B p65 (NF-κB p65) protein levels were measured by Western blot analysis. Tumour necrosis factor (TNF)-α and interleukin (IL)-1β levels were determined by enzyme-linked immunosorbent assays. Results In the I/R group, the W/D, LIS, AI, miR-21 mRNA, TLR4, NF-κB p65, TNF-α and IL-1β were significantly increased and the PaO2 was decreased compared with the sham group. Evidence of lung injury was observed in the I/R group and this was alleviated in the I/R+Cur group. An inhibitor of miR-21 (antagomir-21) reversed the protective effects of curcumin. Conclusion Curcumin post-treatment can alleviate the lung injuries induced by limb ischaemia-reperfusion via downregulating the levels of miR-21 mRNA.

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Effects of cyclosporin A pre-treatment combined with etomidate post-treatment on lung injury induced by limb ischemia-reperfusion in rats

Cited by 5 publications

References 25 publications

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Post-treatment curcumin reduced ischemia–reperfusion-induced pulmonary injury via the Notch2/Hes-1 pathway

Tacrolimus Prevents Mechanical and Humoral Alterations in Brain Death–induced Lung Injury in Pigs

The mechanism of curcumin post-treatment relieving lung injuries by regulating miR-21/TLR4/NF-κB signalling pathway

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