The synthesis of poly-gamma-glutamyl derivatives of 7-hydroxymethotrexate (7-OH-4-NH2-10-CH3-pteroyl-glutamic acid (PteGlu1] was evaluated by direct hydroxylation of the tetraglutamyl derivative of methotrexate (4-NH2-10-CH3-PteGlu4) by a cell-free preparation of rabbit liver aldehyde oxidase and by polyglutamylation of 7-OH-methotrexate in Ehrlich ascites tumor cells in vitro. The polyglutamyl...

background: methotrexate has an important role in treatment of acute leukemia. we measured methotrexate level in csf and blood of children with acute lymphoblastic leukemia to determine complications and outcomes. materials and methods: one hundred and twenty patients (73 male, 47 female), with mean age at diagnosis of 6.1 years (11mo_15years) entered the study. patients were divided into two g...

background and aims: methotrexate (mtx), a folic acid antagonist, is widely used as a treatment for malignancies as well as in the treatment of various inflammatory and autoimmune disorders. nephrotoxicity is an important side-effect of this drug. prevention and treatment of mtx-induced renal dysfunction are essential to prevent potentially life-threatening mtx-associated toxicities, present st...

introduction : methotrexate (mtx) is an anti folate drug that used in malignant and non malignant patients. the usage of high dose methotrexate was limited to patients with: osteogenic sarcoma, ewing sarcoma and lymphoma. the aim this study was to determine the toxicity or side effects of very high dose methotrexate (8-10 gr/m 2 /cycle). this study is the first study in iranian patients and one...

background increases in aminotransferases (transaminitis) are potential major adverse reactions seen with long-term use of methotrexate (mtx). the aim of this study, therefore was to evaluate the incidence of mtx induced hepatotoxicity and its risk factors among rheumatoid arthritis (ra) patients. methods this retrospective study described 286 patients with ra who received ≤ 7.5 mg mtx weekly...

A wild-type Datura innoxia cell line (Px4) was used to select methotrexate-resistant cells through a stepwise procedure. Two independently selected cell lines, MTX161 and MTX132, were stable and shown to be 5 to 15 times more resistant to methotrexate than wild type. These methotrexate-resistant cells were similar to the wild-type cells in levels and kinetic properties of dihydrofolate reductas...

The intracellular accumulation of poly-gamma-glutamyl derivatives of methotrexate was evaluated in the presence of vincristine or probenecid (agents which raise the intracellular level of free methotrexate) in Ehrlich ascites tumor cells. The results show that both intracellular methotrexate and its metabolites are increased by these agents and that, in the presence of L-glutamine, polyglutamat...

The effects of folinic acid on a toxic pulse exposure of cultured hepatoma cells to methotrexate (4-amino-10-methylpteroylglutamic acid) is reported. Inclusion of folinic acid (5formyl-5,6,7,8-tetrahydropteroylglutamic acid) (10/~M) with the 2-hr pulse of methotrexate (10/~M) nearly completely prevents the uptake and y-glutamylation of methotrexate and prevents toxicity. Addition of folinic aci...

Probenecid has been shown to delay the plasma clearance of methotrexate in the rat and to reduce both hepatic and renal excretion of methotrexate in this animal model. In order to probe the mechanism by which probenecid alters hepatic excretion of the antifolate, studies assessed the effects of probenecid on transport, accumulation, distribution, and release of methotrexate in the rat hepatocyt...

The folate analog, methotrexate, binds very tightly to dihydrofolate reductase. However, free intracellular methotrexate in excess of the enzyme-binding capacity is needed to suppress cellular dihydrofolate reduction, and the effects of methotrexate are rapidly reversible if methotrexate is removed from the extracellular media. The apparent paradox may be explained on the basis of a single high...