Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning

Wu, Liaozhang; Cen, Yifang; Feng, Mei; Zhou, Yanna; Tang, Hui; Liao, Xueli; Wang, Yanze; Wang, Min; Zhou, Manhong

doi:10.1155/2019/1709718

Cited by 35 publications

(31 citation statements)

References 33 publications

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“…Studies have shown that metformin alleviates inflammation and protects against acute lung injuries in several animal models. First, metformin treatment significantly reduces lipopolysaccharide (LPS)-induced lung destruction and paraquat poisoning-induced acute lung injury (42)(43)(44)(45). Second, metformin attenuates lung injury caused by the high pressure of mechanical ventilation (46).…”

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confidence: 99%

Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury

et al. 2020

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The pandemic of coronavirus disease 2019 (COVID-19), a disease which causes severe lung injury and multiple organ damage, presents an urgent need for new drugs. The case severity and fatality of COVID-19 are associated with excessive inflammation, namely, a cytokine storm. Metformin, a widely used drug to treat type 2 diabetes (T2D) mellitus and metabolic syndrome, has immunomodulatory activity that reduces the production of proinflammatory cytokines using macrophages and causes the formation of neutrophil extracellular traps (NETs). Metformin also inhibits the cytokine production of pathogenic Th1 and Th17 cells. Importantly, treatment with metformin alleviates various lung injuries in preclinical animal models. In addition, a recent proteomic study revealed that metformin has the potential to directly inhibit SARS-CoV-2 infection. Furthermore, retrospective clinical studies have revealed that metformin treatment reduces the mortality of T2D with COVID-19. Therefore, metformin has the potential to be repurposed to treat patients with COVID-19 at risk of developing severe illness. This review summarizes the immune pathogenesis of SARS-CoV-2 and addresses the effects of metformin on inhibiting cytokine storms and preventing SARS-CoV-2 infection, as well as its side effects.

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confidence: 99%

Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury

et al. 2020

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“…Animal models are frequently used in basic researches to study the function of drugs or molecules, and rats are frequently used as models of PQ‐induced lung injury 21,22 . Besides, type II rat alveolar epithelial cells (RLE‐6TN) are frequently used for in vitro studies in the toxicity of PQ 23,24 . Compared to the type I alveolar cell, type II cell has the potential of division, proliferation and differentiation into type I cells, and they can repair the damaged epithelium.…”

Section: Introductionmentioning

confidence: 99%

“…21,22 Besides, type II rat alveolar epithelial cells (RLE-6TN) are frequently used for in vitro studies in the toxicity of PQ. 23,24 Compared to the type I alveolar cell, type II cell has the potential of division, proliferation and differentiation into type I cells, and they can repair the damaged epithelium. Damage of type II alveolar cells may reduce the surfactant on alveoli, leading to lung oedema and respiratory distress, which is concert with the features of PQ-induced rats.…”

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confidence: 99%

Thal protects against paraquat‐induced lung injury through a microRNA‐141/HDAC6/IκBα‐NF‐κB axis in rat and cell models

Zheng

Zhu

Zhang

et al. 2020

Basic Clin Pharma Tox

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Paraquat (1,1-dichloro-4,4-bipyridine, PQ) is a widely used herbicide in agriculture and with extremely potent toxicity that leads to serious public health problem once misused. By accidental or voluntary ingestion, PQ poisoning results in numerous deaths annually, mainly in developing countries where PQ is more largely used. 2 In oral ingestion cases, the mortality rate is over 90%. 3 PQ poisoning through oral, skin and respiratory tracts contributes to multiple organ failure including lungs, kidneys, liver and nervous system, in which the lung is the primary target organ. 4,5 This phenomenon was attributed to high affinity of PQ to alveolar cells. 6 Therefore, PQ poisonings usually cause acute lung injury and, ultimately, acute respiratory distress syndrome and death. 7 Unfortunately, despite the large volume of studies in the past

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“…However, it is lethal to human and animals when ingested orally and there are still no effective and specific antidotes for PQ. Patients with acute PQ poisoning usually died within several days to weeks after confirmed exposure due to hypoxemia or multiple organs failure, which causes a considerable economic burden and increased medical resource use for families and countries [3][4][5][6]. Therefore, for patients, especially in critically ill patients, clinical outcome evaluation and risk assessment in a timely manner is crucial and essential for medical resources using wisely, which has become a public health problem concerned by doctors and patients, as well as social security agency.…”

Section: Introductionmentioning

confidence: 99%

A Novel and Simple Risk Model Predicts the Prognosis for Patients with Paraquat Poisoning

Gao

Liu

Li³

et al. 2020

SSRN Journal

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Background: Acute paraquat (PQ) poisoning is characterized by multi-organ failure and lacking effective therapies. Therefore, identifying risk factors and developing model that could predict early prognosis for patients with PQ poisoning is of great importance. Methods: This was a retrospective cohort study employed with patients suffered from acute PQ poisoning (n=1199). Patients (n=913) with PQ poisoning from 2011 to 2018 were randomly divided into 2 mutually exclusive groups: training (609 patients) and test (304 patients). Another 2 external cohorts containing 207 cases from Zhengzhou 2019 were used as validation from different time and 79 from Shenyang as validation from different site. Risk factors were identified by a logistic model with Markov Chain Monte Carlo (MCMC) simulation and further evaluated by a latent class analysis. The prediction score of this model was developed based on the training sample and was further evaluated using the testing and validation samples. Results: Eight risk factors including age, ingestion volume, CK-MB, platelet (PLT), white blood cell (WBC), neutrophil counts (N), gamma-glutamyl transferase (GGT) and serum creatinine (Cr) were identified as in dependent risk indicators of in-hospital death events. The risk model had a C statistic of 0.895 (95% CI 0.855-0.928), 0.891 (95% CI 0.848-0.932) and 0.829 (95% CI 0.455-1.000) and a predictive range of 4.6%-98.2%, 2.3%-94.9% and 0%-12.5% for the test, validation_time and validation_site group, respectively. In the training group, the risk model classified 18.4%, 59.9% and 21.7% of patients into the high, average and low-risk groups, with corresponding probabilities of 0.985, 0.365, and 0.03 for in-hospital death events. Conclusion: Eight risk factors were identified in this study. And we developed and evaluated a simple risk model to predict the prognosis of patients with acute PQ poisoning. This simple and reliable risk score system could be helpful in recognizing high-risk patients and reducing in-hospital death rate due to PQ poisoning.

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Metformin Activates the Protective Effects of the AMPK Pathway in Acute Lung Injury Caused by Paraquat Poisoning

Cited by 35 publications

References 33 publications

Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury

Immunomodulatory and Antiviral Activity of Metformin and Its Potential Implications in Treating Coronavirus Disease 2019 and Lung Injury

Thal protects against paraquat‐induced lung injury through a microRNA‐141/HDAC6/IκBα‐NF‐κB axis in rat and cell models

A Novel and Simple Risk Model Predicts the Prognosis for Patients with Paraquat Poisoning

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