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己酮可可碱在管理新冠病毒感染炎症性疾病中的应用前景。

A raising dawn of pentoxifylline in management of inflammatory disorders in Covid-19.

机构信息

Pharmacology Department and Health Research Unit, Medical College, Jouf University, Jouf, Saudi Arabia.

Department of Clinical Pharmacology and Medicine, College of Medicine, ALmustansiriyia University, M.B.Ch.B, FRCP, Baghdad, Iraq.

出版信息

Inflammopharmacology. 2022 Jun;30(3):799-809. doi: 10.1007/s10787-022-00993-1. Epub 2022 Apr 29.

Abstract

The existing pandemic viral infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) leads to coronavirus disease 2019 (Covid-19). SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as an entry-point into affected cells and down-regulation of ACE2 by this virus triggers the release of pro-inflammatory cytokines and up-regulation of angiotensin II. These changes may lead to hypercytokinemia and the development of cytokine storm with the development of acute lung injury and acute respiratory distress syndrome. Different repurposed had been in use in the management of Covid-19, one of these agents is pentoxifylline (PTX) which has anti-inflammatory and antioxidant properties. Therefore, the objective of the present mini-review is to highlight the potential role of PTX in Covid-19 regarding its anti-inflammatory and antioxidant effects. PTX is a non-selective phosphodiesterase inhibitor that increases intracellular cyclic adenosine monophosphate which stimulates protein kinase A and inhibits leukotriene and tumor necrosis factor. PTX has antiviral, anti-inflammatory and immunomodulatory effects, thus it may attenuate SARS-CoV-2-induced hyperinflammation and related complications. As well, PTX can reduce hyper-viscosity and coagulopathy in Covid-19 through increasing red blood cell deformability and inhibition of platelet aggregations. In conclusion, PTX is a non-selective phosphodiesterase drug, that has anti-inflammatory and antioxidant effects thereby can reduce SARS-CoV-2 infection-hyperinflammation and oxidative stress. Besides, PTX improves red blood cells (RBCs) deformability and reduces blood viscosity so can mitigate Covid-19-induced hyper-viscosity and RBCs hyper-aggregation which is linked with the development of coagulopathy. Taken together, PTX seems to be an effective agent against Covid-19 severity.

摘要

由严重急性呼吸系统综合征冠状病毒 2 型(SARS-CoV-2)引起的现有大流行病毒感染导致 2019 年冠状病毒病(Covid-19)。SARS-CoV-2 利用血管紧张素转换酶 2(ACE2)作为进入受影响细胞的切入点,这种病毒下调 ACE2 会触发促炎细胞因子的释放和血管紧张素 II 的上调。这些变化可能导致细胞因子过度释放和细胞因子风暴的发展,从而导致急性肺损伤和急性呼吸窘迫综合征的发生。在 Covid-19 的治疗中已经使用了不同的药物,其中一种药物是己酮可可碱(PTX),它具有抗炎和抗氧化作用。因此,本迷你综述的目的是强调 PTX 在 Covid-19 中的潜在作用,因为它具有抗炎和抗氧化作用。PTX 是一种非选择性磷酸二酯酶抑制剂,可增加细胞内环磷酸腺苷,刺激蛋白激酶 A 并抑制白三烯和肿瘤坏死因子。PTX 具有抗病毒、抗炎和免疫调节作用,因此可能减轻 SARS-CoV-2 诱导的过度炎症及其相关并发症。此外,PTX 通过增加红细胞变形性和抑制血小板聚集,可降低 Covid-19 中的高粘度和凝血异常。总之,PTX 是一种非选择性磷酸二酯酶药物,具有抗炎和抗氧化作用,可减少 SARS-CoV-2 感染引起的过度炎症和氧化应激。此外,PTX 可改善红细胞(RBC)的变形性并降低血液粘度,从而减轻 Covid-19 引起的高粘度和 RBC 过度聚集,这与凝血异常的发生有关。综上所述,PTX 似乎是一种对抗 Covid-19 严重程度的有效药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4984/9051499/f2cb775d10f8/10787_2022_993_Fig1_HTML.jpg

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