Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034063 (pulmonary edema)
 10,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were exposed under static conditions to phosgene at concentrations within the LCt50 range and above. Lungs were removed at various postexposure intervals. Degrees of pulmonary edema were estimated by increases in percentage of water in the lungs of exposed groups as opposed to control animals. Lungs were fractionated into four major subcellular organelle fractions: nuclear debris, mitochondrial-lysosomal, microsomal, and soluble (cytoplasmic). Activities of p-nitrophenyl phosphatase, cytochrome C oxidase, ATP'ase, and LDH within these fractions were decreased after phosgene exposure. There was a concomitant increase in serum LDH levels. One possible mechanism that may play a role in phosgene damage can be associated with either inhibition or loss of enzyme activities from the lung.
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PMID:Effect of phosgene on rat lungs after single high-level exposure. 20 Dec 20

[methyl-14C]-3-Methylindole (3MI) was incubated with goat-lung microsomes, an NADPH-generating system and glutathione. An adduct between an oxidative metabolite of 3MI and glutathione was formed only when the complete system was employed. The adduct, which was detected by u.v. absorbance and scintillation counting of h.p.l.c. fractions, was purified to homogeneity by reverse-phase h.p.l.c. The ability of 3MI to bind to microsomal protein was reduced to 52% and 46% of controls when 2 mM and 4 mM glutathione, respectively, were included in the incubations. These results suggest the involvement of an electrophilic metabolite as the toxic intermediate in 3MI-mediated pulmonary oedema.
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PMID:Electrophilic metabolites of 3-methylindole as toxic intermediates in pulmonary oedema. 650 69

Primary thiomides such as thiobenzamide (TB) are well known hepatotoxins in the rat. Among para-substituted TB derivatives relative hepatotoxicity varies in accordance with the electronic properties of the parasubstituent. In contrast, several N-substituted TBs have been found to be potent lung toxins in rats and mice. For N-methylthiobenzamide (NMTB) the LD50 was found to be 0.315 (95% confidence interval (CI) 0.228-0.436) mmol/kg in the rat and 0.224 (95% CI 0.191--0.264) mmol/kg in the mouse. The N-mono-substituted TBs produce alveolar and perivascular pulmonary edema, together with massive pleural effusions (hydrothorax). In this regard their toxicity resembles qualitatively that of the arylthioureas. Furthermore, pretreatment of rats with sub-lethal doses of NMTB was found to protect them against subsequent challenge with supra-lethal doses. N,N-Dimethylthiobenzamide (DMTB) also causes lung injury in the rat, but only at much higher doses than with the N-mono-substituted TBs. The similarity in toxic responses elicited by the N-mono-substituted TBs and the arylthioureas is paralleled by similarities in their chemical structures and their metabolic disposition which involves (among other things) S-oxygenation by the microsomal flavin-containing monooxygenase (EC 1.14.13.8). Thus, a possible role for S-oxidized metabolites in the lung toxicity of these compounds must be considered.
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PMID:Pneumotoxic effects of thiobenzamide derivatives. 708 87

The antioxidant and anti-inflammatory activities of two transition metal complexes of bioflavonoid rutin, Fe(rut)Cl(3) and Cu(rut)Cl(2), were studied. It was found that Cu(rut)Cl(2) was a highly efficient in vitro and ex vivo free radical scavenger that sharply decreased (by 2-30 times compared to the parent rutin): oxygen radical production by xanthine oxidase, rat liver microsomes, and rat peritoneal macrophages; the formation of thiobarbituric acid-reactive products in microsomal lipid peroxidation; and the generation of oxygen radicals by broncho-alveolar cells from bleomycin-treated rats. The copper-rutin complex was also a superior inhibitor of inflammatory and fibrotic processes (characterized by such parameters as macrophage/neutrophil ratio, wet lung weight, total protein content, and hydroxyproline concentration) in the bleomycin-treated rats. The antioxidant activity of Fe(rut)Cl(3) was much lower and in some cases approached that of rutin. Fe(rut)Cl(3) also stimulated to some degree spontaneous oxygen radical production by macrophages. We suggested that the superior antioxidant and anti-inflammatory activity of the copper-rutin complex is a consequence of its acquiring the additional superoxide-dismuting copper center. The inhibitory activity of Fe(rut)Cl(3) was lower, probably due to the partial reduction into Fe(rut)Cl(2) in the presence of biological reductants; however, similarly to the copper-rutin complex, this complex efficiently suppressed lung edema.
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PMID:Enhancement of antioxidant and anti-inflammatory activities of bioflavonoid rutin by complexation with transition metals. 1126 52

Thiourea-based molecules cause pulmonary edema when administered to rats at relatively low doses. However, rats survive normally lethal doses after prior exposure to a lower, nonlethal dose; this phenomenon is known as tolerance. The present study investigated the morphological and functional aspects of acute lung injury (ALI) induced by methylphenylthiourea (MPTU) in the Wistar rat and the pulmonary response involved in prevention of the injury. We identified pulmonary endothelial cells as the main target of acute MPTU injury; they exhibited ultrastructural alterations that can result in increased vascular permeability. In tolerant rats, the lungs showed only transient endothelial changes, at 24-hour post dosing, and mild type II pneumocyte hyperplasia on day 7 post dosing. They exhibited glutathione levels similar to the controls and increased expression of flavin-containing monooxygenase 1 (FMO1), the enzyme responsible for bioactivation of small thioureas in the laboratory rat. Incubation of rat pulmonary microsomal preparations with MPTU inhibited FMO activity, indicating that tolerance is related to irreversible inhibition of FMOs. The rat model of thiourea-induced pulmonary toxicity and tolerance represents an interesting approach to investigate certain aspects of the pathogenesis of ALI and therapeutic approaches to lung diseases, such as acute respiratory distress syndrome.
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PMID:Morphological and Mechanistic Aspects of Thiourea-Induced Acute Lung Injury and Tolerance in the Rat. 3281 62