Interaction of methotrexate with lipotropic factors in rat liver.

@article{Tuma1975InteractionOM,
  title={Interaction of methotrexate with lipotropic factors in rat liver.},
  author={D. Tuma and A. J. Barak and M. Sorrell},
  journal={Biochemical pharmacology},
  year={1975},
  volume={24 13-14},
  pages={
          1327-31
        }
}
Abstract Methotrexate (MTX), a drug used in cancer chemotherapy and in the treatment of psoriasis, is known to impair DNA and RNA synthesis by antagonizing folate metabolism. A major side-effect of this drug is the formation of a fatty liver and eventual cirrhosis of the liver. Since levels of certain lipotropic substances in the liver are also synthesized de novo by way of folate-dependent 1-carbon metabolism, this study was conducted to determine if the side-effects of MTX may be a… Expand
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References

SHOWING 1-10 OF 25 REFERENCES
THE MECHANISM OF ACTION OF THE FOLATE ANTAGONISTS IN MAN.
TLDR
A knowledge of the ability of leukemic cells to transport and retain amethopterin may be of value in the prediction of responsiveness to therapy with this agent, as well as other factors that deserve further investigation are cited that may also influence responsiveness. Expand
The relative toxicites of methotrexate and aminopterin.
TLDR
The results support the hypothesis that, in some species, the greater toxicity of aminopterin (as compared with that of methotrexate) is attributable to the lesser ability of am inopterin to serve as a substrate for hepatic aldehyde oxidase. Expand
Effects of folic acid metabolism on serum cholesterol levels.
  • G. Bazzano
  • Medicine
  • Archives of internal medicine
  • 1969
TLDR
A return of serum cholesterol to normal levels has been observed in all patients after folate administration, and a definite statistical correlation between serum cholesterol levels and serum folate levels up to 6.2 mug/ml has been established. Expand
Treatment of leukemia with large doses of methotrexate and folinic acid: clinical-biochemical correlates.
TLDR
Patients with acute leukemia were given repeated cycles consisting of infusions of methotrexate followed by "rescue" with folinic acid, and the rates of incorporation of thymidine and of deoxyuridine into deoxyribonucleic acid (DNA) were measuared in vitro. Expand
The recovery of liver tetrahydrofolate dehydrogenase activity from inhibition by methotrexate.
TLDR
Experiments using tritiated methotrexate indicated that both in vivo and in vitro, recovery of enzymic activity is probably associated with a dissociation of the enzyme-inhibitor complex. Expand
Hepatotoxicity of methotrexate in the treatment of psoriasis.
Fifty patients with psoriasis were evaluated prospectively and retrospectively for possible hepatotoxicity from methotrexate therapy. Liver function studies were not reliable indicators of pathologicExpand
The interaction of folic acid derivatives in the methylation of homocysteine.
TLDR
The cobalamin-dependent and -independent mechanisms of homocysteine methylation were both inhibited by reduced derivatives of aminopterin in a similar manner and it was tentatively concluded that the inhibition was due to a competitive interaction between the folates for N(5)N(10)-methylenetetrahydrofolate reductase. Expand
THE ROLE OF VITAMIN B12 IN METHYL TRANSFER TO HOMOCYSTEINE *
TLDR
It is concluded that two reactions are of basic importance in the synthesis of methionine-methyl from a one-carbon unit at the oxidation level of formaldehyde. Expand
DRUG REACTIONS XV
TLDR
The 2 years since 1969 have seen intensive retrospective investigation of methotrexatetreated psoriatic patients in many centres, by liver biopsy as well as by more conventional means. Expand
NEW APPROACHES TO CHEMOTHERAPY WITH FOLATE ANTAGONISTS: USE OF LEUCOVORIN “RESCUE” AND ENZYMIC FOLATE DEPLETION *
TLDR
This paper will be concerned with two new concepts in folate antagonist chemotherapy, namely the use of leucovorin “rescue” to improve the therapeutic index of amethopterin (Methotrexate) (MTX), and theUse of an enzyme, carboxypeptidase G,, to cause folate depletion. Expand
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3
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