Long-term treatment of the MRL/lpr mouse with methotrexate and 10-deazaaminopterin.
Female MRL/lpr mice were treated with I.P. doses of methotrexate (MTX) and 10-deazaaminopterin (DAAM) in the range of 1 to 100 mg/kg body weight/week, in two equally divided doses. Treatment began at 7 weeks of age and continued to 30 weeks of age. Joint histopathology scores were tightly correlated with skin lesion-proteinuria scores at 30 weeks of age. MTX at levels of 5, 25, and 100 mg/kg body weight/week and DAAM at a level of 25 mg/kg body weight/week significantly reduced skin lesion-proteinuria scores below controls in a dose dependent manner. Animals receiving MTX at 25 mg/kg body weight/week had a significantly longer median life span and animals receiving MTX at 100 mg/kg body weight/week had a greater than 15% suppression of growth when compared with controls. Longevity and skin lesion-proteinuria scores appeared to be good indicators of drug efficacy while growth suppression appeared to be a good indicator of drug toxicity.
Baggott
J E
JE
Department of Nutrition Sciences, University of Alabama, Birmingham 35294.
Morgan
S L
SL
Freeberg
L E
LE
Hudson
B B
BB
Vaughn
W H
WH
Gopal Nair
M
M
Krumdieck
C L
CL
Koopman
W J
WJ
Gay
R E
RE
Gay
S
S
D000630:Aminopterin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000473:pathology; D001806:Blood Urea Nitrogen; D003872:Dermatitis / Q000188:drug therapy / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007596:Joints / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use*; D051379:Mice; D011507:Proteinuria / Q000188:drug therapy / Q000276:immunology
D000630:Aminopterin; C017178:10-deazaaminopterin; D008727:Methotrexate