Pulmonary Toxicity of Thioureas in the Rat

Abstract

Administration of a-naphthylthiourea (ANTU) to rats causes damage to pulmonary endothelial cells and possibly mesothelial lining ceils that together may account for the massive pleural effusion characteristic of thiourea toxicity. Using 35S-thiourea as a model compound, the extent of binding of 35S to lung proteins correlated weli with the extent of edema, suggesting that the extent of binding of thiourea metabolites is a measure of lung toxicity. ANTU and phenylthiourea (PTU) compete for 35S binding to lung slices, suggesting that these toxins may act in a similar way. Binding of 35S in lung slices from resistant rats is much less than in controls, and resistance cannot be explained by differences in either whole body metabolism or redistribution of thiourea in vivo. Lung glutathione levels (in vitro and in vivo) in normal and resistant rats foliowing thiourea administration were essentially the same. However, at doses ofthiourea that cause pleural effusion, there was an increase in total lung glutathione.

Effect of the endothelin receptor antagonist tezosentan on alpha‐naphthylthiourea‐induced lung injury in rats

“…The majority of edemagenic agents enhance the passage of fluid into the alveolar airways, presumably by damaging the alveolar epithelium lining, resulting in alveolar edema. However, ANTU causes severe PE, possibly because of the sensitivity of the mesothelial cell lining layer and because it targets capillary endothelial cells [14]. The exact mechanism responsible for the formation of PE is unclear, but we postulate that the acute inhibitory effects of tezosentan on fluid accumulation have a greater effect on the pleural cavity than the interstitial compartment in this model of ALI.…”

“…Alpha‐naphthylthiourea (ANTU), a widely used rodenticide, causes ALI in a dose‐dependent manner by changing the permeability of the lung microvasculature [14]. Because the effects of ANTU are specifically directed at the lungs, the use of this agent has become a popular means of investigating the physiological changes that result from acute lung injury [15–17].…”

Oxyhalogen–Sulfur Chemistry: Kinetics and Mechanism of Oxidation of 1,3-Dimethylthiourea by Acidic Bromate

“…Since the general path to metabolic activation of DMTU is oxidative (specifically through S-oxygenation), a thorough knowledge of its oxidation mechanism as well as its oxidation metabolites should be essential in any attempts at rationalizing DMTU’s physiological effects. Previously, we studied the oxidation mechanisms of substituted thioureas, and no generic oxidation pathways were obtained. − Physiological effects of substituted thioureas span a wide range, also suggesting their oxidative bioactivation mechanisms are also different. − We report, in this manuscript, on the oxidation of DMTU by acidic bromate and bromine. We used bromate as an oxidant because it is a precursor to HOBr, hypobromous acid.…”

Silver recovery from greywater: Role of competing cations and regeneration

“…The reuse of thiourea was an intended goal of the study. Thiourea reuse makes the process sustainable and environmental friendly, as thiourea is toxic [59] and its disposal is a concern.…”