Dimethylthiourea consumption reflects H2O2 concentrations and severity of acute lung injury

Abstract

Even though dimethylthiourea (DMTU) effectively scavenges O2 metabolites in vitro, it is often unclear if scavenging of O2 metabolites is the mechanism by which DMTU decreases tissue injury in biological models. Since DMTU not only scavenges O2 metabolites but is also consumed in a dose-response manner following reaction with hydrogen peroxide (H2O2) in vitro, we wondered whether DMTU would also be consumed by O2 metabolites in biological systems and if DMTU consumption would then reflect O2 metabolite concentrations and O2 metabolite-mediated injury. Our results supported this possibility. We found that selected nonprotecting concentrations of DMTU were consumed in isolated rat lungs perfused with H2O2 and that the amounts of DMTU consumed reflected both the added amounts of H2O2 and the corresponding degrees of H2O2-induced acute edematous injury. DMTU consumption was relatively specific for reaction with H2O2 occurring in isolated lungs that were injured by H2O2 but not lungs injured by elastase, oleic acid, histamine, or a venous pressure challenge. Our results suggest that measurement of DMTU consumption may be useful for assessing the presence and toxicity of O2 metabolites and the specificity of the protective effects of DMTU in biological systems.

Inhaled Birch Pollen Extract Induces Airway Hyperresponsiveness via Oxidative Stress but Independently of Pollen-Intrinsic NADPH Oxidase Activity, or the TLR4–TRIF Pathway

“…We also tested 150 mg/kg NAC administered topically and concomitantly with the allergen, in the same intratracheal 60 μl bolus with BPEx. The antioxidant DMTU, a potent scavenger of oxygen metabolites (21,22), was alternatively administered i.p. at a dose of 100 mg/kg in 0.5 ml sterile PBS (pH 7.2), as previously described to prevent chlorine oxidant-induced lung injury (23) (control animals received 0.5 ml of sterile PBS).…”

Dimethylthiourea protects against chlorine induced changes in airway function in a murine model of irritant induced asthma

“…For this purpose we used dimethylthiourea (DMTU), an oxygen metabolite scavenger [10], that is highly cell-permeable [11-13]. We also wished to examine the effects of Cl 2 on markers of oxidative stress and whether DMTU attenuated these effects.…”

Effects of the superoxide radical scavenger superoxide dismutase, and of the hydroxyl radical scavenger mannitol, on reperfusion injury in isolated rabbit hearts

“…In fact, it has been shown that dimethyl-thiourea, mercaptopropionyl-glycine, and other SH-containing compounds can also inactivate the powerful oxidant hypochlorous acid [41][42][43]. Furthermore, dimethyl-thiourea is also an effective scavenger of hydrogen peroxide [44], and it has recently been shown to protect cardiac myocytes from hypoxic injury by inhibition of Na÷-Ca 2÷ exchange, and not by its antioxidant effects [45].…”