Disease relevance of RV 144

• Erdosteine is a thiol derivative developed for the treatment of chronic obstructive bronchitis, including acute infective exacerbation of chronic bronchitis [1].
• Clinical studies in patients with chronic obstructive lung disease have demonstrated the efficacy and tolerability of erdosteine [1].
• Although hypertonic saline aerosol and erdosteine in patients with bronchitis, and amiloride aerosol in patients with cystic fibrosis have been shown to improve mucus clearance, their clinical utility has not been adequately studied [2].
• The effects of aminoguanidine and erdosteine on the bleomycin-induced lung fibrosis were evaluated in rats [3].
• Comparison of the effects of erdosteine and N-acetylcysteine on apoptosis regulation in endotoxin-induced acute lung injury [4].

High impact information on RV 144

• Erdosteine modulates mucus production and viscosity and increases mucociliary transport, thereby improving expectoration [1].
• Erdosteine significantly increased antibiotic concentrations in sputum but not in serum [5].
• Twenty four patients with acute infective exacerbations of chronic bronchitis received amoxycillin alone or in combination with erdosteine (a mucolytic agent) for a week in a double blind, placebo controlled study [5].
• Erdosteine treatment with rotenone led to an increase in catalase (CAT) and superoxide dismutase (SOD) activities in comparison with the rotenone group (P < 0.05) [6].
• The rats treated with rotenone plus erdosteine produced a significant decrease in lipid peroxidation and XO activities in comparison with rotenone group (P < 0.05) [6].

Chemical compound and disease context of RV 144

• Bleomycin produced a fivefold increase in fibrosis score that was decreased by 87% by erdosteine (P>0.001) and almost twofold increases in hydroxyproline content which were completely prevented by erdosteine [7].
• Cisplatin-induced acute renal failure is ameliorated by erdosteine in a dose-dependent manner [8].
• Erdosteine against acetaminophen induced renal toxicity [9].
• The results obtained suggested that the glucose metabolizing metabolic pathways of renal tissue were partially affected from cisplatin toxicity and erdosteine have some protective effects on these enzyme activities [10].

Biological context of RV 144

• Bleomycin administration resulted in prominent lung fibrosis as measured by lung hydroxyproline content and lung histology, which is completely prevented by erdosteine and aminoguanidine [3].
• It is concluded that oxidative tubular damage plays an important role in the VCM-induced nephrotoxicity and the modulation of oxidative stress with erdosteine reduces the VCM-induced kidney damage both at the biochemical and histological levels [11].
• Regulation of sepsis-induced apoptosis of pulmonary cells by posttreatment of erdosteine and N-aceylcysteine [12].
• The pharmacokinetics of erdosteine and theophylline were also studied [13].
• A combination of budesonide and the SH-metabolite I of erdosteine acts synergistically in reducing chemiluminescence during human neutrophil respiratory burst [14].

Anatomical context of RV 144

• Protection of erdosteine on smoke-induced peripheral neutrophil dysfunction both in healthy and in bronchitic smokers [15].
• There were a significant dilatation of tubular lumens, extensive epithelial cell vacuolization, atrophy, desquamation, and necrosis in VCM-treated rats more than those of the control and the erdosteine groups [11].
• The aim of this study was to investigate whether erdosteine has a protective effect against spinal cord ischemia during aortic cross clamping [16].
• After metabolization, erdosteine (a mucoactive drug) produces an active metabolite (Met I) with an SH group that is capable of opening disulphide bonds, including those of pilin, a protein of bacterial fimbriae [17].
• Erdosteine treatment ameliorated lipid peroxidation after torsion/detorsion in ipsilateral testis (p < 0.05) [18].

Associations of RV 144 with other chemical compounds

• Female Wistar rats were given oral erdosteine (10-500 mg kg(-1)) or N-acetylcysteine (10-500 mg kg(-1)) once a day for 3 consecutive days [4].
• Bleomycin-induced decrease in GSH and SOD levels in the lung tissue also prevented by erdosteine [(GSH levels were 213.5 +/- 12.4, 253.2+/- 25.2, and 287.9+/- 34.4 nmol/mg protein) (SOD levels were 1.42+/- 0.12, 1.75+/- 0.17, and 1.89+/- 0.09 U/mg protein) in BLM, BLM + ERD, and control groups respectively] [19].
• The protective effect of vitamin E on lung histology was stronger than that of erdosteine or NAC [20].
• This study was carried out to investigate comparatively the frequency of apoptosis in lung epithelial cells after intratracheal instillation of endotoxin [lipopolysaccharide (LPS)] in rats and the role of tumor necrosis factor alpha (TNF-alpha) on apoptosis, and the effects of erdosteine and N-acetylcysteine on the regulation of apoptosis [4].
• Erdosteine has positive effects on mucus rheology and transport due to the active metabolite (Metabolite I) which contains a free thiol group [21].

Gene context of RV 144

• The effects of NAC on apoptosis, the increases in the local production of TNF-alpha and VEGF, were weaker than the effects of erdosteine [12].
• The erythrocyte catalase (CAT) activity of Dxr plus erdosteine group was higher than control and Dxr groups [22].
• Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities [23].
• On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production [24].
• We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH [24].

Analytical, diagnostic and therapeutic context of RV 144

• Furthermore, erdosteine administration led to an increase in antioxidant enzyme activities in comparison with the control group [25].
• In erdosteine group, the administration of erdosteine solution (50 mg/kg) was started two days before aortic cross-clamping and rabbits (n=8) were subjected to ischemia and reperfusion [16].
• The results indicate that 8 months of treatment with erdosteine is effective in reducing exacerbation and hospitalization rates and in improving health status [26].
• HPLC with on-line mass spectrometry detection application to elucidate erdosteine metabolism: preliminary study [27].
• The experiment on PMN from healthy smokers (in a double-blind crossover design versus placebo) has indicated that the chemotaxis can be improved only after treatment with erdosteine [15].

References