Effect of fudosteine on mucin production

Rhee, Chin Kook; Kang, Chun; You, Moon Bin; Yoon, Hyung Kyu; Kim, Y K; Kim, K H; Moon, Hwa Sik; Park, S H; Song, Junmin

doi:10.1183/09031936.00018508

Cited by 30 publications

(29 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At this dose, erdosteine was effective in reducing blood ROS levels in patients with COPD 65. Finally, fudosteine shows better bioavailability than NAC and reduces mucus secretion by inhibiting MUC5AC gene expression 66. Other potential therapeutic agents that are under development include Nrf2 activators, spin traps, redox sensor inhibitors, polyphenols, and enzyme mimetics, the details of which are beyond the scope of the current review 67,68…”

Section: Efficacy Of Antioxidant Supplementation In Preventing Progrementioning

confidence: 99%

Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease

Tse¹,

Tseng²

2014

COPD

View full text Add to dashboard Cite

Chronic obstructive pulmonary disease (COPD) is a common and morbid disease characterized by high oxidative stress. Its pathogenesis is complex, and involves excessive oxidative stress (redox imbalance), protease/antiprotease imbalance, inflammation, apoptosis, and autoimmunity. Among these, oxidative stress has a pivotal role in the pathogenesis of COPD by initiating and mediating various redox-sensitive signal transduction pathways and gene expression. The protective physiological mechanisms of the redox balance in the human body, their role in the pathogenesis of COPD, and the clinical correlation between oxidative stress and COPD are reviewed in this paper. N-acetylcysteine (NAC) is a mucolytic agent with both antioxidant and anti-inflammatory properties. This paper also reviews the use of NAC in patients with COPD, especially the dose-dependent properties of NAC, eg, its effects on lung function and the exacerbation rate in patients with the disease. Earlier data from BRONCUS (the Bronchitis Randomized on NAC Cost-Utility Study) did not suggest that NAC was beneficial in patients with COPD, only indicating that it reduced exacerbation in an “inhaled steroid-naïve” subgroup. With regard to the dose-dependent properties of NAC, two recent randomized controlled Chinese trials suggested that high-dose NAC (1,200 mg daily) can reduce exacerbations in patients with COPD, especially in those with an earlier (moderately severe) stage of disease, and also in those who are at high risk of exacerbations. However, there was no significant effect on symptoms or quality of life in patients receiving NAC. Further studies are warranted to investigate the effect of NAC at higher doses in non-Chinese patients with COPD.

show abstract

Section: Efficacy Of Antioxidant Supplementation In Preventing Progrementioning

confidence: 99%

Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease

Tse¹,

Tseng²

2014

COPD

View full text Add to dashboard Cite

show abstract

“…Fudosteine decreased the number of goblet cells increased by lipopolysaccharide or b-stimulant in airway epithelium, and increased serous secretion in broncho-alveolar lavage fluid (BALF) of rats. It also has already reported that fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogenactivated protein kinase in vivo and extracellular signalrelated kinase in vitro [1,2].…”

Section: Introductionmentioning

confidence: 94%

Quantitative Analysis of Fudosteine in Human Plasma Using a Simple Precipitation Step Followed by LC–MS–MS

et al. 2012

View full text Add to dashboard Cite

Fudosteine [(-)-(R)-2-amino-3-(3-hydroxypropylthio) propionic acid] is a synthetic derivative of L-cysteine as a novel expectorant. To facilitate pharmacokinetics studies of fudosteine in man, a sensitive and specific LC-MS-MS method for the quantitative detection of fudosteine in human plasma was developed and validated. The method involved the addition of fosfomycin as internal standards, protein-precipitation, HPLC separation, and quantification by MS/MS system using negative electrospray ionization in the multiple reaction monitoring mode. The precursor ? product ion transitions were monitored at 177.6 ? 90.9 and 136.8 ? 78.9 for fudosteine and the IS, respectively. The lower limit of quantitation (LLOQ) was 5 ng mL -1 . The calibration curves for fudosteine was linear over a concentration range of 0.005-10 lg mL -1 . The intra-and inter-day analyses of QC samples at 0.01, 1, 10 lg mL -1 indicated good precision %RSD between 92.00 and 101.02%. The fudosteine was stable in human plasma stored at room temperature for at least 12 h, 4°C for at least 12 h, -20°C for at least 20 days, and at least three freeze-thaw cycles procedures. This accurate and highly specific assay provides a useful method for evaluating the pharmacokinetics of fudosteine in human.

show abstract

“…Fudosteine, [(−)-(R)-2-amino-3-(3-hydroxypropylthio)] propionic acid (Fig 2), has been used in the treatment of chronic respiratory diseases, such as bronchial asthma, chronic bronchitis, pulmonary emphysema, COPD, and bronchiectasis as a mucoactive agent [156–157]. Fudosteine acts by increasing cysteine levels of the cells and has greater bioavailability than NAC.…”

Section: Small Molecule Thiol Antioxidantsmentioning

confidence: 99%

“…Fudosteine acts by increasing cysteine levels of the cells and has greater bioavailability than NAC. Fudosteine downregulates MUC5AC gene expression thus inhibits mucin hypersecretion [156]. Although, little is known about its mode of action, fudosteine has shown some promising potential in treatment of patients with COPD [158].…”

Section: Small Molecule Thiol Antioxidantsmentioning

confidence: 99%

Pharmacological antioxidant strategies as therapeutic interventions for COPD

Rahman

2012

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

100

View full text Add to dashboard Cite

Cigarette/tobacco smoke/biomass fuel-induced oxidative and aldehyde/carbonyl stress are intimately associated with the progression and exacerbation of chronic obstructive pulmonary disease (COPD). Therefore, targeting systemic and local oxidative stress with antioxidants/redox modulating agents, or boosting the endogenous levels of antioxidants are likely to have beneficial effects in the treatment/management of COPD. Various antioxidant agents, such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn, erdosteine, fudosteine, ergothioneine, and carbocysteine), all have been reported to modulate various cellular and biochemical aspects of COPD. These antioxidants have been found to scavenge and detoxify free radicals and oxidants, regulate of glutathione biosynthesis, control nuclear factor-kappaB (NF-kappaB) activation, and hence inhibiting inflammatory gene expression. Synthetic molecules, such as specific spin traps like α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419, iNOS inhibitors, lipid peroxidation inhibitors/blockers edaravone, and lazaroids/tirilazad have also been shown to have beneficial effects by inhibiting the cigarette smoke-induced inflammatory responses and other carbonyl/oxidative stress-induced cellular alterations. A variety of oxidants, free radicals, and carbonyls/aldehydes are implicated in the pathogenesis of COPD, it is therefore, possible that therapeutic administration or supplementation of multiple antioxidants and/or boosting the endogenous levels of antioxidants will be beneficial in the treatment of COPD. This review discusses various novel pharmacological approaches adopted to enhance lung antioxidant levels, and various emerging beneficial and/or prophylactic effects of antioxidant therapeutics in halting or intervening the progression of COPD.

show abstract

Effect of fudosteine on mucin production

Cited by 30 publications

References 21 publications

Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease

Update on the pathological processes, molecular biology, and clinical utility of N-acetylcysteine in chronic obstructive pulmonary disease

Quantitative Analysis of Fudosteine in Human Plasma Using a Simple Precipitation Step Followed by LC–MS–MS

Pharmacological antioxidant strategies as therapeutic interventions for COPD

Contact Info

Product

Resources

About