title: A whey-based glutathione-enhancing diet decreases allergen-induced airway contraction in a guinea-pig model of asthma.
abstract: Since an allergen-induced early asthmatic reaction is likely to be accompanied by oxidative stress and since levels of the endogenous antioxidant glutathione can be enhanced by a whey-based diet (undenatured whey protein concentrate, UWPC), it was investigated whether UWPC could alleviate allergen-induced lung contractions. Guinea pigs were fed water or UWPC twice a day starting at day - 3 up to day 20. The animals were sensitised to ovalbumin or received saline on day 0. Serum samples were taken at several days after sensitisation to measure allergen-specific IgG. On day 20, lungs were isolated and perfused with buffer containing the allergen ovalbumin. Airway contractions were assessed, and mediators and indicators for oxidative stress were measured in the lung effluent. Moreover, glutathione levels were determined in the liver. The indicator of oxidative stress and airway contractile mediator, 8-iso-PGF(2α), was increased upon ovalbumin challenge in ovalbumin-sensitised groups. Furthermore, thiobarbituric acid-reactive substances (TBARS) were increased as well. Sensitisation with ovalbumin increased IgG levels from day 12 up to day 20, which were not influenced by the UWPC diet. In contrast, the UWPC diet significantly enhanced glutathione levels in the liver. Moreover, the UWPC diet significantly reduced the ovalbumin-induced anaphylactic response by 45 % and decreased PGE2 levels by 55 % in the effluent fluid. We show for the first time that during anaphylaxis, there is acute oxidative stress in the respiratory tract. The UWPC diet did not influence the sensitisation response to the allergen but did increase endogenous glutathione levels. The UWPC diet profoundly reduces allergen-induced airway constrictions, which opens new avenues for dietary management of allergic diseases.
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Sciences, Utrecht University, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Kloek
authors.forename: E
authors.initials: E
authors.lastname: Mortaz
authors.forename: I
authors.initials: I
authors.lastname: Van Ark
authors.forename: N
authors.initials: N
authors.lastname: Bloksma
authors.forename: J
authors.initials: J
authors.lastname: Garssen
authors.forename: F P
authors.initials: FP
authors.lastname: Nijkamp
authors.forename: G
authors.initials: G
authors.lastname: Folkerts
mesh_terms: D000818:Animals; D001249:Asthma / Q000178:diet therapy*; D016084:Bronchoconstriction; D004195:Disease Models, Animal; D005978:Glutathione / Q000008:administration & dosage*; D006168:Guinea Pigs; D008297:Male; D008894:Milk Proteins; D018384:Oxidative Stress; D000067816:Whey Proteins
chemical_list: D008894:Milk Proteins; D000067816:Whey Proteins; D005978:Glutathione