title: Long-term treatment of the MRL/lpr mouse with methotrexate and 10-deazaaminopterin.
abstract: 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.
authors.affiliation: Department of Nutrition Sciences, University of Alabama, Birmingham 35294.
authors.forename: J E
authors.initials: JE
authors.lastname: Baggott
authors.forename: S L
authors.initials: SL
authors.lastname: Morgan
authors.forename: L E
authors.initials: LE
authors.lastname: Freeberg
authors.forename: B B
authors.initials: BB
authors.lastname: Hudson
authors.forename: W H
authors.initials: WH
authors.lastname: Vaughn
authors.forename: M
authors.initials: M
authors.lastname: Gopal Nair
authors.forename: C L
authors.initials: CL
authors.lastname: Krumdieck
authors.forename: W J
authors.initials: WJ
authors.lastname: Koopman
authors.forename: R E
authors.initials: RE
authors.lastname: Gay
authors.forename: S
authors.initials: S
authors.lastname: Gay
mesh_terms: 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
chemical_list: D000630:Aminopterin; C017178:10-deazaaminopterin; D008727:Methotrexate