Effects of the new nitrosourea derivative, fotemustine, on the glutathione reductase activity in rat tissues in vivo and in isolated rat hepatocytes
| Autor: | Jean-Pierre Bizzari, Annie Genton, Claude Cudennec, Marie Paraire, Gilbert Lavielle, Peter Moldéus, Jean A. Boutin, Kajsa Norbeck |
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| Rok vydání: | 1989 |
| Předmět: |
Male
Nitrosourea Antineoplastic Agents Cell Separation Biology Diquat Nitrosourea Compounds chemistry.chemical_compound Organophosphorus Compounds In vivo medicine Animals Lung Carcinogen Carmustine Glutathione Rats Inbred F344 Rats Glutathione Reductase Liver Oncology Biochemistry chemistry Enzyme inhibitor biology.protein Fotemustine medicine.drug |
| Zdroj: | European Journal of Cancer and Clinical Oncology. 25:1311-1316 |
| ISSN: | 0277-5379 |
| DOI: | 10.1016/0277-5379(89)90078-3 |
| Popis: | Fotemustine, a new clinically active nitrosourea, is demonstrated herein to be a poor inhibitor of glutathione reductase activity from rat liver, lung and kidney cytosols. In order to show that an intracellular step of activation does not lead to a toxic intermediary metabolite, rat hepatocytes were incubated with fotemustine. Their glutathione-related pathways were checked and shown not to be altered, while under similar experimental conditions BCNU was shown to be dramatically harmful. Furthermore, association of fotemustine with a H 2 O 2 production leading drug, diquat, was shown to be inefficient—while BCNU is efficient—in potentiating the diquat toxicity. Considering the role of glutathione level in the detoxification of mutagens and carcinogens, the advantage of foemustine over BCNU in therapeutic use seems substantiated. |
| Databáze: | OpenAIRE |
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