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Abstract - ,”” - i, , - 179 - CONCLUSION , l. The analgesic nephropathy is well r ecoqn Ls ed ove r ! long period. An important partial explanation iii the I ’ inhibition of local synthesis of PG in the kt~ney. Neverthless this effect does not invariably occur in ftll NSAIOs. The identity of the ~nalgesics involved a~d the ,pa~hogen~sis of the lesion remain contraversial. This work aimed at studying the implicatiprt of , I , adjuvent induced polyarthritis in ra ts( as aq.’experiillental ,-;,”” ” ; model of rheumatoid-arthritis) on some biochemical and histopathological parameters of kidney function nam~ly, (serum urea, serum creatinine and H Iii & E section o~ :k,id”; ney). Moreover, the effect o’f four widely used, ~~At~s , , ’ ’Ii” , , I namely Pirprofen, diclofenac, indomethacin and pirbx l’cam on the. above:’ menti,oned parameters arthritio rat. wa•• tudied. i ! in adjuvant in,du, ced To aohieve this ’goal, the rats were divided into six groups, each one was comprised of thirty animals., The first one served as nor,mal control which it i’, non- ” , arthritic, non- treated rats in which we administer only daily orally l’ml of gum arabic mucilage, the second one served to study the effect of experimental polyarthritis on rehal function. Experimental polyarthritis was induced j1 --’,,---_.- ----- -----. ._------.’-_. __ .. -------’ , -’ _ .. -’. --- • - 180 - by single intradermal 0.05 ml of FCA which conta in 0 .:4mg’ ! I of mycobacterium injected at ,the base tail of ra,ts (Bar .• bier et al •• 1986). The full blown picture of arthr-iiHs, I: i was achieved after 16 days of the single intradermal , Ilitl~ ! ,, , jection of FCA, this group was not treated with any d~s! i ’ The other four groups, of arthritic rats were daily Clr~~lY ; :! !(I· administrqtion ot: pirprofen (20 mg/kg) dielofehac (2imojJ/:, I : ’! • iii kg) ,indomethacin (3mg/kg) and piroxicam 11 mg/kg) r~H; I’ Ii • pe c t.LveLy , ,, ,, The drug administration was begun aHer : I i ! the appearance Of, full blown picture of poiyC\rthriltH: (after the 16th day of the single intradermal inject~~rt ,, of FCA). The choice of the doses depend on publis,hed i·”: literatures and pilot experiment. The doses of variou, s, drugs hav~ equivalent antiinflammatory potency. , , ii , animal ’groups were subdevided into three sUbgroups. The il’he I; ’ first subgroup were sacrified after ten days of daily’ , oral administration of drug, the second subgroup was ---’ -. I . - • .. I sacrified ,after twenty’days .and the third one was saci:i-’ ”l fied after tllrity days . • ’:j All animals were subjected to ’the folloWing experimental proc,dures: ’! l.· , i ” I ~, ---,~-- ~ i-: :’) - 181 - - Serum urea level - seru~ creatinine level H & E. sect.joon of the kidney ; Arthritic non treated rats showed immunologically, med.iated nephro.toxici ty in the form of some glomerular shrunkage, some tubular degeneration and cyst formation., Serum creatinine level was significantly increased compared with normal group at 10, 20 and 30 days. Serum urea level was a l sc s igni ficantly increased compared, wit~ normal rats after 10 and 30 days,but after twenty days ’of treatment, it !’las pa~lIdoxically decreased compared with ;er~m u~ea’ after t~n days of treatment. T~is . . , is due to some. improvemen.t of inflammatory cOt,t,cHtion. ! ” The most severe microscopical lesions was encountered with pirprofen which showed progress ive tubular’ degeneration, papillary necrosis, interstitial focal necros is wi th lymphocytic infi 1tration, the glomeruiar showed hypercel~ularity and cresent formation. Setum ’creatinine level and,serum urea level was signirican~ly progressively increaSed after thrity days ”f daily. drUg administration. ’” Serum urea level was increased after ten days, of daily drug administration but the serum urea level was . -- _._’ -’ - -_ .. , ,, - 182 paradoxically decreased after twenty days of daily d~ug’ administration compared with the results after 10 and :30, days. The nephrotoxicity of pirprofen was attributed to i~ strong PGinhibito~y effect, on the other hand, pir~ profen being a propionic acid derivative can activate , cel’lular immunological reaction which may lead to nephr o-, toxicity especially glomerular lesion and to its phar~a-, , cokiiletic character’that faver its intrarena1 conl=e~t!-” i ’ , ration. Concerning diclofenac treated group,diclof_nae’ caused milder nephrotoxIc reaction than pirprofen ’’’d indomethl!lcln. Serum creatinine level s igni f icantly! , increased compared with arthritic non treated rats after thirty days of daily drug administration. i Serum Urea level significantly increased compared ~ith arthritic non treated rats after ten days and after thirty days : i of daily drug administration. Its nephrotoxicity may be due to its local selac”” tive renal concentration, high renal tubular reabsorption of, the drug, as a result of its pharmaeokinetic ! ; properties as well as through PG inhibition. I The daily administration of indomethacin resulted, in marked’ renal toxicity in the form of tubular degeneration. C++l, interstitial necrosis together with hyperctUlularit¥Qf . ! ,’U ,,. ’ ,~ ---”--- -_ ..- -----._ .•..._- i j .------ ..,’l;”’;’c..’..~_ - 183 - the glomeruli: mild oedema and mild haemorrhage.’ After ! twenty days of daily drug administration.serum cre~tinine , level w.. • i;nif1c:antly h10h1y increaud compared wilh arthritic non treated rats. also it was significantly increased after . thiTty - days of daily drug administration compared with arthritic non trea ted ra ts. Serum urea level was significantly highly increased compared with arthritic non treated rats after ten days and thirty days Of daily dru~ administration. This can be explained on the light of the property of indomethacin being powerful inhibitory -t of prosta\;fl;llndin synthesis. These lead to vasoconstriction of renal vessels with consequent tubular degeneration and pap~llary necrosis. Contrarly to other tes’ted very mild histological lesions. affect serum creatinine level. drug. piroxicam icaused i It did not significaNtly , ; i’ ;’ ., Serum uJ;”e~ level was trans iently decreased ’after ’ twenty days of daily drug administration. The mild i renal effect of piroxicam was due to its weak PO inhib.itory act1vity and due to it. l!avourable pha,rmal;j,olcinetic, pro~ .,,” . pertie. whiC’h prevl.nt high renal concentration ~( the drug, prevent its tubular reab.orption. A more prdlon~.d ! !: ’ study is needed to assess its nephrotoxic potential:. , i The , !I, ,, - ---’~-’-_._~- ! - 194 - pharmacokinetic properties of NSAIDs should be ta~~rl in consideration during prolonged use of these drugsih patients of high risk especially renal patients. A’ more sensitive parameter is needed other than serum urea concentration and’ serum creatinine to moni eo r i nephrotoxicity of NSAIDs. .,I I’ i· i iI ! --------”-- ..... -- .. ----- --- I ’”. II .. I __ f ! i i, ! . , |