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Effects of etodolacTM and naproxen on adjuvant arthritis in the rat
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Efffftsof EKWI.?Cm andNapruxencmI!djwantArthritis in the Rat
lMartel,R., O'Cmmr, D., andWetze1,J. Ayerst ResearchIaboratories
AnimalHealthDivisiar Chazy,Nsw York 12921
lAyerstMcKennaiiRarrisCm,Inc. 1025bmrenti~ Blvd. Saint-Laurent, QuebecH4R lJ6
'IherelativeefficacyOf mlac ad nsprxxenwas exambd histologically and radiologicallyusing the rat djuvant art&it&i mdel. Thirty-six male rats wre divided ~lyinto6groups. &tt~itiswasiduodingrcups2-6bysubcu~sinjecticmof Ebund*son@ete adjwant in the tail. Grrruplservedasa nmarthriticantrol. Gross evi.&nceof arthritisin the hind legs was evidmtby day10 and anti-inflamatoq therapywasbsguncndayl6. Qmps3 and 4 received 2 and 8ng Etabladkg, respectively, andgraqs 5 and 6 rec+xd 2 ad 8rq napruxedkg,respectively. Drugs were~stereddaily~the~oftheshrdy.Grarp2servedasanarthritic positivecontrol. Mdiographsof UKI legsvmxtakenonday16 am3 againat the end of the study on day 44. RatsweIekilledonday44dbothhildlegswereI!emved, X-raysrevealedtissue , erosiaw, and bone loss in all djuvant-treatearats. These dmgess" presentdn days 16 am3 44. Their severitywasgreatestin the positive Rats mceiving 2ng/kg Etadolacor Znq/kg naproxenalso had considerable dsmqe.'ltmsere&ving8ng/kg mqmxen had xess mvere dmnges, while rats reosiving 8mg/kgRW&lacm far less-. Microsa@zexaminatim revealed lesionsinthe hind legs of all rats which receivedca@ete sdjuvant. These changesrepresented a Fs\qithkrvlDlvene?tof~~purfacesana.~iatea~,hcnes,and . SvbJectiveseverity samlng ldlcated that InflarmatoIy joint disease in grmp4 rate (Snq/kg Rtc&lac) was amsizy2d3 si?ficantly less severethan in all other adjwant-injectedanimsls. ad 6 were histologically irdistinguiddlefran each otherand arthritisd i&se l-ats was of amrked to severe nature. AterIudl~,Etodolacwasbet~abkthanneproxgntoretardtheproqres~ of djwant arthritis.
Anticholinesterase activityin rats follaring sublethal oral and intravenous doses of carbosulfan (2,3-dihydr~-2,2-dlirnethyl-7-benzofuranyl[di-n-butylaminosulfenyl][methyl] carbamate)
RENZI, B.E., DEY, M.S., KRIEGER. R.I. AND TANAKA, A.K.,* WOI Regional Program in Veterinary Medical Education, University of Idaho, Moscow, Idaho 83843 and *Division of Toxicology and Physiology. Department of Entanology, University of California, Riverside, California 92521.
a selective N-methyl carbamate Sublethal mammalian toxfclty of carbosulfan, (AChE) insecticide, was characterlteo in rats. Red blood cell acetylcholinesterase actlvltv was measured usina a radianetrlc assay. Female Sprague-Dawley rats (220-3169) with jugular cannulas u&e-given oral or intravenous dosages of 86.4, 245 or 692 *g/kg. Proovlene elvcol was administered (0.4 ml/kg) orally or intravenously as the vehicle -.a 4- or 5-hour test period. control. Bio&I smples (0.2 ml) were drawn throughout AChE was saximally inhibited (62, 77 and 83%) one minute after iv administration of AChE activity had returned to carbosulfan (86.4. 245 and 692 ug/kg, respectively). pretreatwent levels at 4 hours. Maximtan AChE Inhibition (36%) was measured 45 minutes after oral adninlstratfon of 692 ug/kg and enzyme activity returned to pretreatment levels after approximately 5 hours. Signs of toxictty included urlnation, defecation. facial muscle fasciculatlons and, at the two higher Iv dosages, salivation and tremors. Carbosulfan causes a dose-related Inhlbitlon of RBC acetylchclinesterase and has loner toxicity when given orally. (Supported in part by NIH Bluaedica. Research Development Grant 1 5OB RR 09073-OlA2).
Efffftsof EKWI.?Cm andNapruxencmI!djwantArthritis in the Rat
lMartel,R., O'Cmmr, D., andWetze1,J. Ayerst ResearchIaboratories
AnimalHealthDivisiar Chazy,Nsw York 12921
lAyerstMcKennaiiRarrisCm,Inc. 1025bmrenti~ Blvd. Saint-Laurent, QuebecH4R lJ6
'IherelativeefficacyOf mlac ad nsprxxenwas exambd histologically and radiologicallyusing the rat djuvant art&it&i mdel. Thirty-six male rats wre divided ~lyinto6groups. &tt~itiswasiduodingrcups2-6bysubcu~sinjecticmof Ebund*son@ete adjwant in the tail. Grrruplservedasa nmarthriticantrol. Gross evi.&nceof arthritisin the hind legs was evidmtby day10 and anti-inflamatoq therapywasbsguncndayl6. Qmps3 and 4 received 2 and 8ng Etabladkg, respectively, andgraqs 5 and 6 rec+xd 2 ad 8rq napruxedkg,respectively. Drugs were~stereddaily~the~oftheshrdy.Grarp2servedasanarthritic positivecontrol. Mdiographsof UKI legsvmxtakenonday16 am3 againat the end of the study on day 44. RatsweIekilledonday44dbothhildlegswereI!emved, X-raysrevealedtissue , erosiaw, and bone loss in all djuvant-treatearats. These dmgess" presentdn days 16 am3 44. Their severitywasgreatestin the positive Rats mceiving 2ng/kg Etadolacor Znq/kg naproxenalso had considerable dsmqe.'ltmsere&ving8ng/kg mqmxen had xess mvere dmnges, while rats reosiving 8mg/kgRW&lacm far less-. Microsa@zexaminatim revealed lesionsinthe hind legs of all rats which receivedca@ete sdjuvant. These changesrepresented a Fs\qithkrvlDlvene?tof~~purfacesana.~iatea~,hcnes,and . SvbJectiveseverity samlng ldlcated that InflarmatoIy joint disease in grmp4 rate (Snq/kg Rtc&lac) was amsizy2d3 si?ficantly less severethan in all other adjwant-injectedanimsls. ad 6 were histologically irdistinguiddlefran each otherand arthritisd i&se l-ats was of amrked to severe nature. AterIudl~,Etodolacwasbet~abkthanneproxgntoretardtheproqres~ of djwant arthritis.
Anticholinesterase activityin rats follaring sublethal oral and intravenous doses of carbosulfan (2,3-dihydr~-2,2-dlirnethyl-7-benzofuranyl[di-n-butylaminosulfenyl][methyl] carbamate)
RENZI, B.E., DEY, M.S., KRIEGER. R.I. AND TANAKA, A.K.,* WOI Regional Program in Veterinary Medical Education, University of Idaho, Moscow, Idaho 83843 and *Division of Toxicology and Physiology. Department of Entanology, University of California, Riverside, California 92521.
a selective N-methyl carbamate Sublethal mammalian toxfclty of carbosulfan, (AChE) insecticide, was characterlteo in rats. Red blood cell acetylcholinesterase actlvltv was measured usina a radianetrlc assay. Female Sprague-Dawley rats (220-3169) with jugular cannulas u&e-given oral or intravenous dosages of 86.4, 245 or 692 *g/kg. Proovlene elvcol was administered (0.4 ml/kg) orally or intravenously as the vehicle -.a 4- or 5-hour test period. control. Bio&I smples (0.2 ml) were drawn throughout AChE was saximally inhibited (62, 77 and 83%) one minute after iv administration of AChE activity had returned to carbosulfan (86.4. 245 and 692 ug/kg, respectively). pretreatwent levels at 4 hours. Maximtan AChE Inhibition (36%) was measured 45 minutes after oral adninlstratfon of 692 ug/kg and enzyme activity returned to pretreatment levels after approximately 5 hours. Signs of toxictty included urlnation, defecation. facial muscle fasciculatlons and, at the two higher Iv dosages, salivation and tremors. Carbosulfan causes a dose-related Inhlbitlon of RBC acetylchclinesterase and has loner toxicity when given orally. (Supported in part by NIH Bluaedica. Research Development Grant 1 5OB RR 09073-OlA2).