The effect of methotrexate on lipoxygenase metabolism in neutrophils from rats: in vitro and ex vivo studies.
Studies were undertaken to examine the effect of methotrexate (MTX) administered in vivo or added in vitro upon the production of the 5-lipoxygenase (5-LO) metabolites of arachidonic acid (AA) by rat neutrophils. Peptone-induced peritoneal exudate cells were stimulated by A23187 and the cell suspensions assayed for leukotriene B4 (LTB4), the all-trans isomers of LTB4 and 5-hydroxyeicosatetraenoic acid (5-HETE) using high-pressure liquid chromatography. MTX added in vitro to rat cells was weakly inhibitory; however, no inhibition of LTB4 production was seen following in vivo administration of MTX by oral, subcutaneous or intraperitoneal routes. On the basis of these findings, inhibition of 5-LO metabolism does not appear to explain the anti-inflammatory effects of MTX.
Hawkes
J S
JS
Rheumatology Unit, Royal Adelaide Hospital, Australia.
Cleland
L G
LG
James
M J
MJ
D000284:Administration, Oral; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D005122:Exudates and Transudates / Q000166:cytology / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D066298:In Vitro Techniques; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007975:Leukotriene B4 / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D007975:Leukotriene B4; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D008084:Lipoxygenase; D008727:Methotrexate