Ornithine decarboxylase induction in mouse kidney as indicator of renal damage. Differential nephrotoxic effect of anticancer antifolate drugs.
High doses of folate and its quinazoline analogue with antitumour activity, N10-propargyl-5,8-dideazafolic acid (CB 3717), caused severe renal damage in mice, leading in the case of folate to death. The mouse kidneys increased in weight, which was accompanied by time- and dose-dependent induction of ornithine decarboxylase (ODC) activity. In contrast, methotrexate (MTX) had negligible effect on mouse kidneys except when applied together with the non-steroidal antiinflammatory drug, indomethacin.
Manteuffel-Cymborowska
M
M
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Warsaw, Poland.
Chmurzyńska
W
W
Grzelakowska-Sztabert
B
B
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D015415:Biomarkers; D004790:Enzyme Induction; D005260:Female; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000633:toxicity*; D005493:Folic Acid Antagonists / Q000633:toxicity; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects* / Q000201:enzymology; D007674:Kidney Diseases / Q000139:chemically induced*; D008727:Methotrexate / Q000633:toxicity*; D051379:Mice; D009929:Organ Size; D009955:Ornithine Decarboxylase / Q000096:biosynthesis*; D011799:Quinazolines / Q000633:toxicity*
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D005493:Folic Acid Antagonists; D011799:Quinazolines; C031662:CB 3717; D005492:Folic Acid; D009955:Ornithine Decarboxylase; D007213:Indomethacin; D008727:Methotrexate