Testing lazaroids U-74389G and U-83836E for therapeutic value in experimental allergic encephalomyelitis in the Lewis rat.
Reactive oxygen intermediates (ROI) and reactive nitrogen intermediates (RNI) are toxic molecules that are thought to play a pathogenic role in many disease states, and data from prior studies indicate a role for ROI and RNI in the pathogenesis of experimental allergic encephalomyelitis (EAE). ROI and RNI can elicit tissue damage by initiating the chain reaction of lipid peroxidation. Lazaroids are a series of compounds that have been shown to interrupt lipid peroxidation. In the present study, the lazaroids, U-74389G and U-83836E, were administered to Lewis rats with EAE in order to evaluate their therapeutic effectiveness. Several different doses and administration routes, which were based on the manufacturer's (Upjohn) recommendations and a prior experimental study, were employed: 1) intraperitoneal injection (IP), 1mg drug/kg body weight, 1x/day from 7-18 days postencephalitogen injection (diseases onset approximately 9 day), male; 2) IP, 1mg/kg, 1x/day from 0-18 days, male; 3) intravenous (IV) cannula, 3mg/kg, 2x/day from 7-18 days, female; 4) IV cannula, 3mg/kg, 2x/day from 7-18 days, male; and 5) IV cannula, 10mg/kg, 2x/day from 7-18 days, female. The weights and clinical signs were evaluated on a daily basis. In all treatment regimens, there was an absence of a statistically significant difference between the vehicle-treated animals and the two groups of drug-treated animals. These data imply that lipid peroxidation may not be an effective therapeutic site in EAE. It is important to note that there are several different types of EAE and our study only explored the EAE model in the Lewis rat.(ABSTRACT TRUNCATED AT 250 WORDS)
Milford
C M
CM
Dept. of Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Lynch
S G
SG
Cross
R S
RS
LeVine
S M
SM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy*; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D008297:Male; D009103:Multiple Sclerosis / Q000188:drug therapy; D010879:Piperazines / Q000494:pharmacology*; D011281:Pregnatrienes / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew
D000975:Antioxidants; D002839:Chromans; D016166:Free Radical Scavengers; D010879:Piperazines; D011281:Pregnatrienes; C074965:U 74389F; C066382:U 78517F