Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The short-term toxicity of 2-hydroxy-1,4-naphthoquinone (lawsone) and 2-methyl-1,4-naphthoquinone (menadione) has been compared in rats. 2-Methyl-1,4-naphthoquinone has been shown previously to cause haemolytic anaemia in animals, and this was confirmed in the present experiment. 2-Hydroxyl-1,4-naphthoquinone was found also to cause haemolysis, in a dose-dependent manner, as reflected by decreased blood packed cell volumes and haemoglobin levels and by histopathological changes in spleen, liver and kidney. With both naphthoquinones, the haemolysis was of the oxidative type, characterized by the presence of Heinz bodies within erythrocytes. Haemolysis was the only toxic change identified in rats dosed with 2-methyl-1,4-naphthoquinone. In contrast, 2-hydroxyl-1,4-naphthoquinone was not only a haemolytic agent but also a nephrotoxin, causing renal enlargement, elevated plasma levels of urea and creatinine and histologically-identified tubular necrosis, largely confined to the distal segment of the proximal convoluted tubules. The relationship between the in vivo toxic effects of these naphthoquinones and previously-reported data on their in vitro cytotoxic action is discussed.
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PMID:Haemolytic activity and nephrotoxicity of 2-hydroxy-1,4-naphthoquinone in rats. 206 55

A phase II trial of menadione (2.5 g/m2 as a continuous intravenous infusion over 48 h) followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4-6 weeks was performed in 43 patients with advanced gastrointestinal cancer. Menadione, a vitamin K analog that lowers intracellular pools of reduced glutathione, was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating-agent chemotherapy. The median age of patients entered on this trial was 58 years; performance status ranged from 60%-100%. None of the 43 evaluable patients obtained an objective response to this combination regimen. Median survival was 6.6 months. Treatment with menadione and mitomycin C was reasonably well tolerated except for hematological toxicity. A total of 27% of treatment courses were complicated by grade 3 or 4 hematological toxicity including one episode of hemolytic anemia and one episode of hemolytic uremic syndrome. One patient developed irreversible interstitial pneumonitis, and 1 patient had an asymptomatic decrease in the left-ventricular ejection fraction. Despite preclinical evidence indicating that menadione pretreatment enhances the cytotoxicity of mitomycin C, our study documents the resistance of advanced gastrointestinal cancers, particularly colorectal cancer, to mitomycin C modulated by menadione.
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PMID:Mitomycin C and menadione for the treatment of advanced gastrointestinal cancers: a phase II trial. 788 72

A phase II trial of menadione [2.5 gm/m2 as a continuous intravenous (i.v.) infusion over 48 hours] followed by mitomycin C (10-20 mg/m2 i.v. bolus) administered every 4 to 6 weeks was performed in 23 patients with advanced lung cancer. Menadione, a vitamin K analog which lowers intracellular pools of reduced glutathione (GSH), was combined with mitomycin C in an attempt to overcome thiol-mediated resistance to alkylating agent chemotherapy. The median age of patients entered on this trial was 62 years; performance status ranged from 60-90%. Two of the 23 patients (9%; 95% confidence interval, 1% to 28%) had objective responses lasting 3.5 months and 13 months respectively, while 4 additional patients developed short unconfirmed responses (lacking follow-up response data to estimate response duration). Median survival for all patients was 5.5 months. Treatment with mitomycin C and menadione was well tolerated except for hematologic toxicity and cardiac events of unclear relationship to the study drugs. Thirty-one percent of treatment courses were complicated by grade 3 or 4 hematologic toxicity including one episode of hemolytic anemia. One patient developed interstitial pneumonitis. Two patients developed a decrease in left ventricular ejection fraction: one patient remained asymptomatic, but the other patient developed congestive heart failure. Although only 9% of patients had confirmed objective responses, 28% (5 of 18) of the patients with non-small cell lung cancer demonstrated biological activity (tumor regression fulfilling the criteria for objective response on a single occasion but 3 patients lacking a follow-up measurement to document response duration) to this combination of mitomycin C and menadione. We conclude that further studies of chemomodulation in non-small cell lung cancer are appropriate.
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PMID:Mitomycin C and menadione for the treatment of lung cancer: a phase II trial. 861 79

Previous studies demonstrated that menadione, a representative quinone compound, reacts nonenzymatically with thiols in plasma, resulting in the generation of reactive oxygen species and potentiation of menadione-induced platelet damage. Because of the reported association of menadione with hemolytic anemia in vivo, investigations were undertaken to identify the free radicals generated from the interaction of menadione with plasma, and to assess the potential role of plasma-generated free-radical species in menadione-dependent erythrocyte toxicity. In rat plasma, menadione increased the rate of oxygen consumption and both luminol- and lucigenin-amplified chemiluminescence in a concentration-dependent manner. Superoxide dismutase (SOD) inhibited lucigenin-amplified chemiluminescence, suggesting formation of superoxide anion. Menadione also induced significant increases in chemiluminescence when erythrocytes were suspended in plasma, but not when cells were suspended in buffer. Consistent with these findings, menadione-dependent hemolysis of erythrocytes occurred only when the cells were suspended in plasma. Various free-radical inhibitors were tested for their ability to inhibit menadione-induced hemolysis. Catalase and mannitol each produced significant inhibition, including an additive effect when both compounds were present, while SOD had no marked effect. In addition, pretreatment with 3-amino-1,2,4-triazole, an intracellular catalase inhibitor, potentiated menadione-induced cytotoxicity in the presence of plasma. These results suggest that both hydrogen peroxide and hydroxyl radicals are involved in menadione-mediated plasma erythrocyte cytotoxicity; however, superoxide anion does not appear to play a direct role.
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PMID:Adverse consequences of erythrocyte exposure to menadione: involvement of reactive oxygen species generation in plasma. 1154 21