title: Mutated glutathione S-transferase in combination with reduced glutathione shows a synergistic effect in ameliorating oxidative stress and airway inflammation.
abstract: Oxidative stress is implicated in the pathogenesis of asthma, and antioxidant levels are reduced in asthma patients. Previously, glutathione S-transferase (GST) with reduced IgE binding suppressed oxidative stress and modulated airway inflammation to some extent in mice. GST catalyzes the quenching of reactive oxygen species by reduced glutathione (GSH) and the absence of any one of them may limit antioxidative behavior. This study evaluates the effects of mutated (m) GST with GSH in combination and individually in limiting oxidative stress and inflammatory responses in a mouse model. BALB/c mice were immunized and challenged with ovalbumin. The mice were treated with mGST, GSH, mGST + GSH, or alpha-lipoic acid by inhalation and sacrificed to evaluate inflammation and oxidative stress parameters. Treatment with the mGST + GSH combination showed significantly reduced total cell (p<0.01) and eosinophil (p<0.01) counts in BALF compared to other groups. The lung inflammation score was lowest for the mGST + GSH group, along with reduced IL-4 (p<0.01) and OVA-specific IgE compared to the other treatment groups. Oxidative stress as per the lipid peroxidation and 8-isoprostane level in BALF of mGST + GSH mice was reduced significantly compared to the individual antioxidants. In conclusion, mGST in combination with GSH has a synergistic effect in reducing airway inflammation compared to the individual antioxidants and has potential for the treatment of asthma.
authors.affiliation: Institute of Genomics and Integrative Biology (Council of Scientific and Industrial Research), Delhi 110 007, India.
authors.forename: Prabhanshu
authors.initials: P
authors.lastname: Tripathi
authors.forename: Smitha
authors.initials: S
authors.lastname: Nair
authors.forename: B P
authors.initials: BP
authors.lastname: Singh
authors.forename: Naveen
authors.initials: N
authors.lastname: Arora
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy*; D004195:Disease Models, Animal; D004357:Drug Synergism; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000235:genetics / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000517:prevention & control; D008171:Lung Diseases / Q000139:chemically induced / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000235:genetics / Q000494:pharmacology*; D009154:Mutation; D010047:Ovalbumin; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000276:immunology; D008063:Thioctic Acid / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D050505:Mutant Proteins; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D010047:Ovalbumin; D005982:Glutathione Transferase; D005978:Glutathione