Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclophosphamide (CP) requires metabolic activation for its therapeutic action, and this metabolism results in the formation of two toxic metabolites, acrolein (ACR) and phosphoramide mustard (PM). To determine which metabolite is responsible for CP-induced lung injury, biochemical indices of toxicity and histopathologic changes in the lungs of CP-, ACR-, or PM-treated rats were evaluated. Experimental rats were given 200 mg kg-1 day-1 CP, 5 mg kg-1 day-1 ACR, or 50 mg kg-1 day-1 PM for 1 to 3 days, or were given 100 mg/kg CP for 1 day; control rats received vehicle alone for 1 to 3 days. Twenty-four hr after the last treatment the lungs were analyzed for (a) microsomal NADPH cytochrome c reductase and aniline hydroxylase activities; (b) microsomal lipid peroxide formation; and (c) glutathione content. In rats given 200 mg/kg CP, NADPH cytochrome c reductase and aniline hydroxylase activities decreased 66% (p less than 0.001) and 40% (p less than 0.001), respectively. Lipid peroxidation was increased 100 to 200% (p less than 0.001), and glutathione content was increased 60 to 70% (p less than 0.001). Similar but smaller changes were observed in the lungs of rats given 100 mg/kg CP. In rats given ACR, NADPH cytochrome c reductase and aniline hydroxylase activities decreased 66% (p less than 0.001) and 45% (p less than 0.001), and glutathione content increased 38% (p less than 0.05). In rats given PM, none of the biochemical variables examined were significantly altered. Phenobarbital and SKF 525-A prevented CP-induced biochemical alterations. Despite CP-induced biochemical alterations, no significant light microscopic changes were observed in the lungs. Alterations in lung mixed-function oxidase activity, GSH content, and microsomal lipid peroxide formation are early biochemical indices of CP-induced lung toxicity, and are due at least in part to the reactive metabolite ACR.
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PMID:Biochemical indices of cyclophosphamide-induced lung toxicity. 643 86

Using histological, morphometric, histochemical and immunocytochemical methods, the effect of cytotoxic treatment on structural and functional characteristics of the epithelium of esophageal mucosa was studied in mice together with the reversibility of the changes induced by cytotoxic drug. Fourfold intraperitoneal injection of cyclophosphamide (400 mg/kg of body mass) resulted in such morpho-functional changes, as thickening of epithelial layer, increase in proportion of its stratum corneum and its loosening, disturbances in cornification process, hyperkeratosis, vacuolization of cell cytoplasm in stratum basale and stratum spinosum, interstitial edema, nuclear hypertrophy and parakeratosis. Mitotic activity and the activity of NADH-diaphorase were significantly reduced, while the number of PCNA' cells was increased. Cyclophosphamide had no significant affect on the concentration of total proteins. 15 days after the discontinuation of cytostatic treatment, most of the indexes did not return to normal values, indicating profound disturbances in the esophageal epithelium.
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PMID:[Morphological and functional changes in the esophageal epithelium after treatment with a cytostatic agent]. 1733 19