Fig. 5: Redox and immune metabolism during acute and chronic cutaneous DTHR.

a Overview of reactive oxygen and nitrogen species (RONS) production by resident and infiltrating immune cells during an immune response initiating the RONS cascade and their scavengers. The most important small molecule RONS scavengers, such as glutathione (GSH), ascorbate and taurine, are illustrated at their site of action. The ear swelling response during the acute cutaneous DTHR peak at 24 h is illustrated by the orange arrow, and the chronic cutaneous DTHR peak at 4 h is illustrated by the blue arrow. b Normalised concentration changes illustrated as box plots with max. to min. whisker, individual replicate points and median of GSH and glutathione disulfide (GSSG) concentration sum, ascorbate and taurine changes during acute 24 h (grey, downward triangle) and chronic 0 h (bright yellow, dot) and 4 h (dark yellow, dot) cutaneous DTHR (compared to naive control (grey, square), P values ****<0.0001, ***<0.001, **<0.01, *<0.05, one-way ANOVA). c Correlation pattern hunter graph of the top 25 most significantly correlated metabolites to glutathione (GSH) concentration changes over time, based on Pearson r distance measure (n = 5 animals, except A 24 h n = 4 animals). DHA dehydroascorbate, GPC sn-glycero-3-phosphocholine, GPX glutathione peroxidase, GRX glutaredoxin, GSSG glutathione disulfide, MPO myeloperoxidase, NADPH reduced nicotinamide adenine dinucleotide phosphate, NOX NADPH oxidase, SOD superoxide dismutase, TauCl taurine chloramine, UDP uridine diphosphate, UOX urate oxidase, XAO xanthine oxidase.