Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)

Lei, Changjiang; Wu, Shixing; Wen, Chong; Li, Yuan; Liu, Ning; Huang, Jianbin; Li, Lei; Fu, Meixia; Liu, Jiani

doi:10.1016/j.intimp.2018.12.056

Cited by 13 publications

(11 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports indicated that the expression of Cysltr1 is upregulated in adenoid hypertrophy (Gao et al, 2018). Activation of Cysltr1 stimulates JNK phosphorylation (Lei et al, 2019), leading to the trigger of inflammation (Kondeti et al, 2016). Knockout of Cysltr1 prevents mice from irritant-induced asthma (McGovern et al, 2016) and also reduces colitis-associated colon cancer (Osman et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury

Liu

et al. 2019

Front. Pharmacol.

View full text Add to dashboard Cite

Acetaminophen (APAP) is a widely used over-the-counter antipyretic and analgesic drug. Overdose of APAP is the leading cause of hospital admission for acute liver failure. Montelukast is an antagonist of cysteinyl leukotriene receptor 1 (Cysltr1), which protects from inflammation and oxidative stress. However, the function of montelukast in APAP-induced hepatotoxicity remains unknown. In this study, we examined whether pharmacological inhibition of Cystlr1 could protect mice against APAP-induced hepatic damage. We found that APAP treatment upregulated messenger RNA and protein levels of Cysltr1 both in vitro and in vivo. Pharmacological inhibition of Cysltr1 by montelukast ameliorated APAP-induced acute liver failure. The hepatoprotective effect of montelukast was associated with upregulation of hepatic glutathione/glutathione disulfide level, reduction in c-Jun-NH2-terminal kinase activation and oxidative stress. In mouse primary hepatocytes, inhibition of Cysltr1 by montelukast ameliorated the expression of inflammatory-related genes and APAP-induced cytotoxicity. We conclude that montelukast may be used to treat APAP-induced acute hepatic injury.

show abstract

Section: Introductionmentioning

confidence: 99%

Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury

Liu

et al. 2019

Front. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Zafirlukast had been reported as a competitive leukotriene receptor antagonist for the treatment of bronchial asthma 27 . Moreover, zafirlukast suppressed ROS in chondrocytes as well as used against cardiovascular disease 28,29 . After in vitro antileishmanial analysis, we observed that zafirlukast did not show many promising results as compared to the standard drug.…”

Section: Discussionmentioning

confidence: 87%

“…27 Moreover, zafirlukast suppressed ROS in chondrocytes as well as used against cardiovascular disease. 28,29 After in vitro antileishmanial analysis, we observed that zafirlukast did not show many promising results as compared to the standard drug. Therefore, we proceeded to the second top hit out of 10, that is avodart, showing a similar binding affinity and predicted inhibitory constant as zafirlukast toward LdSDM.…”

Section: Discussionmentioning

confidence: 96%

Targeting sterol alpha‐14 demethylase of Leishmania donovani to fight against leishmaniasis

Tabrez

Rahman

Ali

et al. 2021

J of Cellular Biochemistry

View full text Add to dashboard Cite

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha‐14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)‐approved drugs against LdSDM to identify the potential lead‐drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra‐macrophagic amastigotes. Avodart‐induced reactive oxygen species (ROS) in the parasites in a dose‐dependent manner. ROS induced by avodart led to the induction of apoptosis‐like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA‐approved drug, avodart, establishing a nice example of the drug‐repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.

show abstract

“…A cell surface receptor that has been recently identified on articular chondrocytes is the type 1 cysteine leukotriene receptor (CysLTR1), which is upregulated in case of AGE accumulation and promotes metalloproteinase secretion via the MAPK, AP‐1, and NF‐κB pathways. This downstream effect can be hampered in vitro by the administration of zafirlukast, a selective CysLTR1 antagonist usually adopted in the treatment of asthma …”

Section: The Role Of Advanced Glycation End‐productsmentioning

confidence: 99%

“…This downstream effect can be hampered in vitro by the administration of zafirlukast, a selective CysLTR1 antagonist usually adopted in the treatment of asthma. 63 Another drug that has unexpectedly shown to counteract the AGE-mediated ECM degradation is memantine, officially licensed to Besides, the synovium isolated from the obese diabetic subjects showed an increased macrophage infiltration and higher TNF-α levels which were not counteracted by insulin, thus demonstrating the existence of an insulin-resistance behaviour within the joint. 70 The insulin receptor is expressed by human articular chondrocytes as well and its activation promotes type II collagen and proteoglycan synthesis through the upregulation of the phosphoinositol-3 kinase (PI3K)/Akt pathway.…”

Section: The Role Of Advanced Glycation End-productsmentioning

confidence: 99%

Osteoarthritis and type 2 diabetes: From pathogenetic factors to therapeutic intervention

Cannata

Vadalà

Ambrosio

et al. 2019

Diabetes Metabolism Res

View full text Add to dashboard Cite

Summary Over the last decades, osteoarthritis (OA) and type 2 diabetes (T2D) prevalence increased due to the global ageing population and the pandemic obesity. They currently affect a substantial part of the Western world population and are characterized by enhancing the risk of disability and reduction of quality of life. OA is a multifactorial condition whose development derives from the interaction between individual and environmental factors: The best known primarily include age, female gender, genetic determinants, articular biomechanics, and obesity (OB). Given the high prevalence of OA and T2D and their association with OB and inflammation, several studies have been conducted to investigate the causative role of biological characteristics proper to T2D on the development of OA. This review aims to analyse the relationship between of OA and T2D, in order to explain the pathophysiological drivers of the degenerative process and to delineate possible targets to which appropriate treatments may be addressed in the near future.

show abstract

Zafirlukast attenuates advanced glycation end-products (AGEs)-induced degradation of articular extracellular matrix (ECM)

Cited by 13 publications

References 20 publications

Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury

Montelukast Prevents Mice Against Acetaminophen-Induced Liver Injury

Targeting sterol alpha‐14 demethylase of Leishmania donovani to fight against leishmaniasis

Osteoarthritis and type 2 diabetes: From pathogenetic factors to therapeutic intervention

Contact Info

Product

Resources

About