Effects of zileuton: A Synthesis of Findings from 28 Studies

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Original Abstract of the Article

Major Research Findings

Zileuton, a selective 5-lipoxygenase (5-LO) inhibitor, has shown potential benefits in various inflammatory diseases, including asthma, spinal cord injury, colitis, and skin conditions. 3 suggests that zileuton might prevent airway smooth muscle remodeling after repeated allergen challenge in rats. 8 reports that zileuton can reduce airway inflammation caused by inhaled swine house dust in healthy subjects. 24 suggests that zileuton can inhibit ferroptosis, a type of cell death, in neurons after spinal cord injury, potentially promoting functional recovery. 12 found that zileuton improved pruritus score, general well-being, and electroencephalographic activity in patients with Sjögren-Larsson syndrome. Other research indicates that zileuton may protect against lung damage during endotoxemia 25 , protect against cardiac ischemia/reperfusion injury 2 , prevent esophageal adenocarcinoma 11 , have anti-inflammatory effects in allergic asthmatics 13 , inhibit pancreatic cancer invasion and metastasis 22 , prevent oral cancer 10 , enhance the effectiveness of temozolomide in treating glioblastoma 19 , improve acute kidney injury 21 , protect against spinal cord injury 6 , suppress cardiomyocyte apoptosis 5 , exert antitumor effects in cervical cancer 1 , and mitigate kidney injury and fibrosis 23 . 26 suggests that zileuton may influence biomarkers associated with tobacco-related carcinogenesis in smokers. 18 found that zileuton can reduce colitis in an experimental rat model. 16 showed that a single dose of zileuton can improve bronchial hyperresponsiveness in asthmatics. 4 reports that zileuton can protect against testicular torsion/detorsion injury in rats. 15 suggests that zileuton can suppress platelet-activating-factor-induced pulmonary abnormalities in mild asthma. 9 indicates that zileuton may affect interleukin-13 secretion from activated murine spleen cells. assesses 5-lipoxygenase activity in vivo by analyzing leukotriene B4 in saliva and examines the effects of treatment with zileuton. 17 provides results from a six-month randomized, multicenter trial on the acute and chronic effects of a 5-lipoxygenase inhibitor in asthma. 14 examines the effects of multiple dosing with zileuton on antigen-induced responses in sheep. 7 suggests that zileuton may influence the development of autoimmune myocarditis in an experimental rat model. 27 reports that a disease-associated missense mutation in CYP4F3 affects the metabolism of leukotriene B4 by disrupting electron transfer. 20 examines the LC-QToF chemical profiling of Euphorbia grantii Oliv. and its potential to inhibit LPS-induced lung inflammation in rats.

Benefits and Risks

Benefit Summary

Research suggests that zileuton, a 5-lipoxygenase inhibitor, may have potential benefits in treating a variety of inflammatory diseases. These potential benefits include reducing airway inflammation, protecting against tissue damage, promoting cell recovery, and easing symptoms of certain conditions.

Risk Summary

While research shows potential benefits, zileuton can cause side effects. Common side effects include digestive issues, headaches, dizziness, and rashes. In rare cases, more serious side effects like liver damage and blood cell reduction may occur. It is crucial to use zileuton under the guidance of a doctor and carefully monitor for any side effects.

Study Comparisons

Similarities in Studies

Across many studies, zileuton demonstrates the ability to reduce inflammation by inhibiting the enzyme 5-lipoxygenase. Research also suggests potential benefits, including anti-inflammatory, cell-protective, and functional recovery effects in various diseases.

Differences in Studies

Research on zileuton varies significantly. The diseases where zileuton shows promise, the effectiveness of different dosages and administration methods, and the reported side effects differ between studies. Therefore, further research is needed to clarify the effectiveness and safety of zileuton.

Consistency and Contradictions in Results

While numerous studies suggest that zileuton might be beneficial for treating inflammatory diseases, the effectiveness and safety of the drug are not consistently demonstrated. Variations in the severity of the diseases, the dosages used, and other factors can influence the outcomes. Further research is needed to establish the reliability of zileuton's effects.

Considerations for Real-World Applications

It is essential to consult with a doctor for a proper diagnosis and treatment plan before using zileuton. Self-medication is not recommended. Regular check-ups with your doctor are crucial to monitor for any side effects.

Limitations of Current Research

Many studies on zileuton rely on animal models or small clinical trials. Larger, more comprehensive clinical trials are necessary to fully confirm the safety and effectiveness of this drug for treating human conditions.

Future Research Directions

Despite the promising potential of zileuton, further research is necessary. Areas that need further investigation include long-term effects, optimal dosage, and the precise mechanisms behind its efficacy in different diseases.

Conclusion

Zileuton, a 5-lipoxygenase inhibitor, has shown potential benefits in treating various inflammatory conditions, but further research is needed to fully understand its effectiveness and safety. If you are considering using zileuton, it is crucial to consult with a doctor and use the drug under their guidance.

Literature analysis of 28 papers
Positive Content
23
Neutral Content
1
Negative Content
4
Article Type
5
0
0
0
28
1.

Zileuton inhibits arachidonate-5-lipoxygenase to exert antitumor effects in preclinical cervical cancer models.

Author: LiLiling, XiaoYifang, XuZhengzheng, WangShaoshuai

Cervical cancer treatment

This study evaluated the efficacy of zileuton, an FDA-approved ALOX5 inhibitor, in treating cervical cancer. Zileuton demonstrated anticancer activity and was shown to regulate ALOX5 expression in cervical cancer patients. The study also investigated the molecular mechanism of action of zileuton in this context.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

2.

The effects of zileuton and montelukast in reperfusion-induced arrhythmias in anesthetized rats.

Author: GoncaErsöz

Heart I/R injury treatment
Arrhythmias

Zileuton and montelukast are drugs used to treat heart ischemia/reperfusion injury, but their effects on arrhythmias are unknown.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

3.

Effects of zileuton on airway smooth muscle remodeling after repeated allergen challenge in brown Norway rats.

Author: ChenWei-Ji, LiawShwu-Fang, LinChing-Chi, LinMei-Wei, ChangFeng-Ting

Beneficial effects on asthma
Reduced bronchial hyperresponsiveness

Zileuton effectively prevented bronchial hyperresponsiveness, airway inflammation and airway smooth muscle (ASM) remodeling in rats sensitized to ovalbumin (OA) by inhibiting the PI3K/Akt pathway, which reduces cyclin D1 expression. This suggests that zileuton can be used to treat chronic asthma.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

The cardioprotective effects of zileuton, a 5-lipoxygenase inhibitor, are mediated by COX-2 via activation of PKC delta.

Author: KwakHyun-Jeong, ParkKyoung-Mi, ChoiHye-Eun, LimHyun-Joung, ParkJin-Hee, ParkHyun-Young

Cardioprotection
Ischemia/reperfusion injury treatment
Unknown

Zileuton, a 5-lipoxygenase inhibitor, exerts a protective effect against cardiomyocyte apoptosis by activating PKC delta and inducing COX-2 expression. This suggests a potential therapeutic strategy for ischemia/reperfusion injury of the heart.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

6.

Effects of zileuton and montelukast in mouse experimental spinal cord injury.

Author: GenoveseT, RossiA, MazzonE, Di PaolaR, MuiàC, CaminitiR, BramantiP, SautebinL, CuzzocreaS

This study examines the role of cysteinyl-leukotrienes (Cys-LTs) in the inflammatory response and tissue injury associated with spinal cord injury (SCI), using a 5-lipoxygenase inhibitor (zileuton) and a Cys-LT receptor antagonist (montelukast).

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

8.

Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects.

Author: LarssonBritt-Marie, KumlinMaria, SundbladBritt-Marie, LarssonKjell, DahlénSven-Erik, PalmbergLena

Increased airway inflammation
Increased bronchial responsiveness

Zileuton, a 5-lipoxygenase inhibitor, did not prevent the increase of bronchial reactivity induced by swine house dust exposure. However, it did completely abolish the LTB4 release in nasal lavage fluid and partially inhibited the formation of leukotrienes in urine.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

9.

Differential effects of hydroxyurea and zileuton on interleukin-13 secretion by activated murine spleen cells: implication on the expression of vascular cell adhesion molecule-1 and vasoocclusion in sickle cell anemia.

Author: KuvibidilaSolo, BaligaB Surendra, GardnerRenee, YuLolie, WarrierRaj, VelezMaria, OdeDavid, HaynesJohnson

Improved SCD status

This study examines the effect of hydroxyurea, a treatment for sickle cell disease, on IL-13 secretion. IL-13 is a cytokine that contributes to vasoocclusion in sickle cell disease.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

10.

Overexpression of 5-lipoxygenase and cyclooxygenase 2 in hamster and human oral cancer and chemopreventive effects of zileuton and celecoxib.

Author: LiNing, SoodSandeep, WangSu, FangMingzhu, WangPeng, SunZheng, YangChung S, ChenXiaoxin

This study aims to evaluate the contribution of the 5-lipoxygenase (5-Lox) pathway to oral carcinogenesis and the potential synergistic or additive effects of combining inhibitors of both the cyclooxygenase (Cox) and 5-Lox pathways.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

11.

Overexpression of 5-lipoxygenase in rat and human esophageal adenocarcinoma and inhibitory effects of zileuton and celecoxib on carcinogenesis.

Author: ChenXiaoxin, WangSu, WuNan, SoodSandeep, WangPeng, JinZhe, BeerDavid G, GiordanoThomas J, LinYong, ShihWei-Chung J, LubetRonald A, YangChung S

Aberrant AA metabolism

Aberrant arachidonic acid metabolism through the 5-lipoxygenase (5-Lox) pathway is implicated in the development of esophageal adenocarcinoma (EAC). Zileuton, a specific 5-Lox inhibitor, shows potential chemopreventive effects in a rat model of EAC.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, U.S. Gov't, P.H.S.Research funding provided by the Public Health Service (PHS).

Language : English

12.

Clinical and biochemical effects of zileuton in patients with the Sjögren-Larsson syndrome.

Author: WillemsenM A, LuttM A, SteijlenP M, CruysbergJ R, van der GraafM, Nijhuis-van der SandenM W, PasmanJ W, MayatepekE, RotteveelJ J

Pruritus treatment

This study investigates the use of zileuton, a leukotriene synthesis inhibitor, for treating Sjögren-Larsson syndrome (SLS). The results suggest potential benefits in reducing pruritus and improving general well-being, but further research is needed to confirm these findings.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

13.

Anti-inflammatory effects of zileuton in a subpopulation of allergic asthmatics.

Author: HasdayJ D, MeltzerS S, MooreW C, WisniewskiP, HebelJ R, LanniC, DubéL M, BleeckerE R

Reduce eosinophils

This study investigated the effects of allergen exposure on leukotriene generation and inflammation within the airways of allergic asthmatics and the effects of the 5-lipoxygenase inhibitor zileuton on these responses. The 5-lipoxygenase inhibitor zileuton reduced postantigen BALF eosinophil count by 68% in patients with high leukotriene levels, but had no detectable effect on BALF composition in patients with low leukotriene levels. Leukotriene inhibition may be more effective in patients with high leukotriene levels.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
Research Support, U.S. Gov't, Non-P.H.S.Research funding provided by US government agencies other than the Public Health Service.

Language : English

14.

The effects of multiple dosing with zileuton on antigen-induced responses in sheep.

Author: ScuriM, AllegraL, AbrahamW M

Reduced airway inflammation

Multiple dosing with the 5-LO inhibitor, zileuton, provides protection against the antigen-induced EAR as well as LAR.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

15.

The effects of 5-lipoxygenase inhibition by zileuton on platelet-activating-factor-induced pulmonary abnormalities in mild asthma.

Author: GómezF P, IglesiaR, RocaJ, BarberàJ A, ChungK F, Rodriguez-RoisinR

Asthma treatment
None reported

Zileuton, a selective 5-lipoxygenase inhibitor, effectively reduces platelet-activating factor (PAF)-induced neutropenia, lung function disturbances, and ventilation-perfusion (VA/Q) defects in patients with mild asthma.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

16.

Effects of single-dose zileuton on bronchial hyperresponsiveness in asthmatic patients treated with inhaled corticosteroids.

Author: DekhuijzenP N, BootsmaG P, WieldersP L, van den BergL R, FestenJ, van HerwaardenC L

Bronchial hyperresponsiveness attenuation

Zileuton, a 5-lipoxygenase inhibitor, attenuated bronchial hyperresponsiveness to histamine and ultrasonically nebulized distilled water in asthmatic patients with marked bronchial hyperresponsiveness.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

17.

Acute and chronic effects of a 5-lipoxygenase inhibitor in asthma: a 6-month randomized multicenter trial. Zileuton Study Group.

Author: LiuM C, DubéL M, LancasterJ

Improved lung function
Reduced asthma symptoms
Reduced beta-agonist use
Reduced need for steroid rescue

Zileuton produces objective and subjective improvements in patients with mild to moderate asthma and is well tolerated.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Effects of zileuton, a new 5-lipoxygenase inhibitor, in experimentally induced colitis in rats.

Author: ZingarelliB, SquadritoF, GrazianiP, CameriniR, CaputiA P

Treat colitis
None mentioned

Zileuton, a 5-lipoxygenase inhibitor, was compared to sulphasalazine in an experimental model of rat colitis. Zileuton was more effective than sulphasalazine in reducing colonic leukotriene levels, inflammation, and tissue damage, suggesting its potential benefit in treating inflammatory bowel diseases.

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

21.

Zileuton ameliorates aminoglycoside and polymyxin-associated acute kidney injury in an animal model.

Author: HudsonCole S, SmithJames E, EalesBrianna M, KajijiShama, LiuXinli, TruongLuan D, TamVincent H

Reduced nephrotoxicity

Aminoglycosides and polymyxins are antibiotics effective against multidrug-resistant Gram-negative bacteria, but they have dose-limiting nephrotoxicity. This study investigated whether zileuton can reduce nephrotoxicity associated with amikacin and polymyxin B in a rat model of acute kidney injury.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

24.

Zileuton Ameliorates Neuronal Ferroptosis and Functional Recovery After Spinal Cord Injury.

Author: SunPiyun, ZhouJinlong, ZhaoTianshu, QiHuiping, QianGuibin

Spinal cord injury complication

This abstract discusses the role of ferroptosis in spinal cord injury (SCI) and whether zileuton (ZIL), a selective 5-lipoxygenase (5-LO) inhibitor, can inhibit ferroptosis in SCI.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

27.

A disease-associated missense mutation in CYP4F3 affects the metabolism of leukotriene B4 via disruption of electron transfer.

Author: SmeetsElien, HuangShengyun, LeeXiao Yin, Van NieuwenhoveErika, HelsenChristine, HandleFlorian, MorisLisa, El KharrazSarah, EerlingsRoy, DevliesWout, WillemsenMathijs, BückenLeoni, PrezzemoloTeresa, Humblet-BaronStephanie, VoetArnout, RochtusAnne, Van SchepdaelAnn, de ZegherFrancis, ClaessensFrank

Immune dysfunction

This case report describes a 26-year-old female with a complex immune phenotype, mainly marked by exhaustion, muscle weakness, and inflammation-related conditions. The cause of her symptoms is unknown, but the involvement of the LTB4 pathway is suspected.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

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