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The evaluation of organs damage in acute lead poisoning
toimpropmuse. handiinganddispasal.Theaim~fthep,e~”tedstuh, wastoavaluatwelfeclsof Oelor 103,nalong-termexperiment Gmups of female W&tar ratswere led alotatdose of 40.2OOand 4Mmghg of Delo, 103 eve, a period of three months. In al: PC&fed gmups. there was a marked increase!n live, P450 content and bye, EROD acwaty However,the developmentof hepatis uropurphyriawas absewed in wneanimak of theZOOand4Wm~groupan~ Although the PC8 administmtbn wes discontinued after fhfee months. lh6 urinarypotphyrin content of some animals continued to rise during the ,ecovew periodand reached a peakst4-6mcnthspost trealment 9monthsalter treatmem. the liuerEROD act&v returnedto control ,ev& but the
at about 2W mgikg. Also. is obvious that’che induciion oimic,oscmalenwmes is not thee& factw respons,blstorthe development of polychlorinatedbiphenyls: porphyria:in viw: bpadperoxi-
This study tested the hypothesis lhat a pepide. correeqonding10 thelirst (HXh motif ofphwa. forms a binsrysandwich in the presswe 0‘ trall~ition metal ton lZnz+ and Nb+). Synthetic peptide I-KHRHRHE-I was linked to a resin bead 0, to biotin. Peptic& .-are mixed and mcubated (1 h, 25-C. 10 mM tns, pH 7.4)wilh and withoulZn2+ 0, Niz+. Theassauation 01 both complexes wes assayed by adding the avidin-alkalinephosphatare. After incubation and washing an associated alkaline phorphatase activitywas ana;minun added metal. ihe foil&ing &&s were obtaned: alk&e pbwphatase activity tmsm i SE: umollminA) wm 6.S f 2.0 miny9 Zn2+ VBRUS20.5 I3.9 plus Zn2+ (p < 0 Olland 5.7 f 1 S m,nw Ni2+ versus 12.4 * 2.1 plus N?+ (p c 0 05). Thacalaredcompkxlonedwhenpeptidelinkedtobiotin(l.5mlM~ wee mixed with NiC12solution IO.75 o, 1.5 mM) and studied bv spw tropbotomeby and circula, dichroism. Tiw spectral absorprion bends ,394 (8.1). ,339 (4.2,. 745 12.71, 1060 14.4,) and CD spectra suggest sn octahedral (high spinl binding mwJe oi Ni (111.These resuhe in-
es a result 01 the lack of &vopwhygii in lead ccmamiwatedenvironments. and byingesliondwingsubrdala~empts 01 wetwwiubk kad compounds.
Obj.&&w The am of tha stud” wbj to ealuale the orgam damage in acute lead paiaamngvia inhaktbn h4afer;afandMertrods:Tha clinicalcou,~? ol acute lead poisoningin 3 males zq., 57.40 and 23 yeem was ~rsected Tw of them were exposedto lead steem dwingths unprofess:onaibenew bumme the tn,,d was exposed during the rwxal making. All the poixlned were sem to the Cliwc Imm the augicai depanrrents of rqonal ho$ptals wh,le hosp~bksabonbecause ot colicky abdominal pain. Tha high blmd lead levels1110. 149. 12E ~9961 and Ihe skvated kvals of caproporphyrinand ULA in urinewere found.
Due to evaluation of organs damage the ultraaonograpky of ab dominal catty. ltetic scmtigraphy and hepaiography. brain computer tomography ek?ctracardiagraphy and echocardiography were per. ‘armed. Resulfs: Any Mary eafculOs~swas nottound in ultrasonographic ex. amination. The static scintigraphv welded an abnormal iknage of liver in efl sublti~. Hepatohifiary dynamic %intigraphy Ihepatglraphy) revealed liver function failure of respectively 45%. 30% end 35%. The brain dystrophywas found in Gland neuropsqchological examination. TM retuft5 Of EEG were normel. Al%? the electrocardiography and echocardiographywere within normel limfts. Conclusions: As the result of ecute lead poisoning the injury of the WerandtheCentml ner”0”S s~ternwere found. Nowm~tomsafc.rdiovarcufar ?.vstem disorders &en noted. The bran computer tomography. staCc liver scintigraphy end hcp atography combined with biochemical end loricologicaf analysis al. lows an appropriate assessment of poisoning severity and evaluation of organs damage
In damaged renal tubules small round epithelial cells exfoliante [I). Thw occurrence m urine is a certain relatively specific index of the deqree of fubulotoxicitv. After e~osure to the “referent* direct tubtab t&s (HgCIZ. amphot&icin 31. ihe intensity of tubular epithelial cells in urine in experimentat rate is twenty times higher comment~ng wth day 2 already after a singiwdose administration. With the use of a referent drug inducing tubuloto%icity in e mediated wey (sub lethal doses of cvclosporine A. inducing an intensive idtw of Caz, into the cells of tfw smwth muscles of the vesw4% reeufting in vesoconstriction with subsequent ischeemi2etion of the ktiney as a organ StrOnQly supplied with blood). the increase in spithelial cells excreted in urine is onhr slwfold end ontv after rawated sdminisiratffn. In an indirect tubuIOtonic agent, this b!agna& test appears to be an earlier parameter than the examinatton glucosaminidese. alanine-amirwpepMaee8).
tento
The snails Amphimelenia fwlandti and Planarhwius CWRBUSvv~reexposed to 0.58 end Ns-PCP for 16 days. The pa,ho,ogicaf alterations ware ftrst evidentin the gills of A. holandri treated with 1 mgll N&PCP for 3 day, and 0.53 mgJ Na.PCP for 4 days. Sufxhronic wprsw@resultedin greeter gill damage. Epithalial necrosis and sloughing were massive and the only recognizable gil .WucWre was the chitinoue rod. The digesbve gland. gonads and kidney were also affected. Exteneive damage of these organs was observed after 6 days. Snail I comeus was more resistanL The fint changes in gonad and digestive gland were Bvident after4daysof exposure to 1 mgtl Na-PCPandaher 6 days of e~w?.“re to 0.56 r”g,l Ne-PCP
t ma”
holandri;
planorbarfus
CO,“B”S:
Manaterf~nes are present in fumes liberated dunng sawing and pmcessing of fresh wood end are e potentisl risk forworkere in sawmills. Turpenhnecondsts 01 a mixture of monoterpenes. karena being one of the major eom~nents. Tsrpenea.espaciallyBcarene. may irrftate tfteskin and rnuccu~ membranesand prolonged expasure may result in $llergfccontactdermaritfla w chronic lung function Impairment. Inhaled 3carane et a concantration ot 5ooO mg& caused bronchwrmstriction in isolated. vemilatad and perfwzd giriia pig fu,lgs. lb@ effectwes inhibited bythecyctooxypanaseinhibItordicfofenac(1W yMf andthethromboxanelproslaglandinendopsroxid~~ceptorantbSon~t L870.598 (1 t&I. 3.csrene exposure atso increased the amount of thromboxanein ihe fwfusate from the lungs and in cultured calf pulmonarvanerialendothelialceflrXarenecausedados~related:elease of arach~dcnicacid. Thus. the results obtained in this experimental models may have implications in the understanding of the pathophysiologyof %careneinduced obPtructivepulmananldi~aea in humrms.
Oturinary enzymes {Nacely!-,3-D-
1119cc~H.Ml,ch9..Ma”eR.SackI:‘Armaim.+worh.lDr”gRs..29.~35.1919
11,L. Llstbwn.Fali.*~lipswA. Soye,S
Keywords: “eph,otox,crty; d,agnostk teet
Studyaf C&ular Effectsof Chloramphmkaland ita Matabdlks Cytotoxk,Gmnofoxlc Effect8md Dan-R#ponre RmkUonshlp C. Fafarge-Frayssinet. S. Robbane-Bemat. C. Frayssinet. L. Toucas. J-M Seigneunn. E Decfoitre. UPR 42 IFC F-94.901 Vdfajui~France The vbjective was to mvesugete the C)nOtoxic and genotoxn: effe~(s of Chlaramtihen~caffCAP~ and six metabolilesiNOCAF! DH-CAl? NPAP NAPD, CAt’G and Hid’) in human cells in o&r to p&se the’natur~ of actwe metaholites, determine dose-response relaricnship and rw effects concentrations. compare the sensitivity of 3 target cells. Methods The human cells used were: peripheral blood lymphocytes IPBL). Raillymphoma cells, immortalized RiBM from humanbane marrow. The cyioloxic effect was mesured by inhibition 01 3H th-,midineincwporatbninDNAandthegenotaxiceffecibydetect~pnof DNA single strands breaks bvakstlne elution &sr&%: three CAP metabolitee: NOCAA DHCAP end NPAE prs. sented a cytotox~c effect: no-effect concentration were comprised between 1 x 10-e M end 2 9 x 10-e M. CAP end NAPD were cytotoxic at much higer cwcenlratfon (0.7 x 10-4 MI. CAPG and HAP wre no toxicupto4 x 1OJ M. NO.CAf? DH-CAPand NPhPweretheonly CAP meldMites producing a gel~ltoxa effect. The weffea concentralion was 2 x We M in P9L and Rail cells: it was supar~or to 2 x 10-e M in RiEM cells with were lower suncsptibleto cqtotaxicand genotoxic eflect of NO.CAFI OH-CAP and NPAP than human PBLand Raiicells.
cells
Mom”, P.Rymdl A,R~spiratmn.
Keywords: Xarene: lung; thmmboxane; bionchoconstrfctian
S&cllronlcTonknyOf SUB
I.& m29
A. LevriC’ D. Tibaut’. K. Culiakz, M. Nsmec3.
’
RbDB,amedical DepbLek’d d Uublana, Shwenie: 2 Dept of f?3fho&,! Univ of Zagreb, Croat%;3 Dept. of&chsmiro: Unl~. ofLjubf,liana.Sfwenia In sxprimeni ot the 30 daw subchmnlc toxicityof ths substance Lek 8828. a new potemial amipsychatic 111.eighty rats of both sexes divided into 4 groups were used. The first grwp wee treated WMhM.0. the second with 159. and the third wth 5.0 malkaldav substance lek 8929 orally. while to the fourth group 1 mlfiglday dtstilled weter wee given. The msults showad that the male and female rats in all amum survived. Neither clinical svmptcmatolow. nor food CODSURID bon.‘nor haematological examine&a% and uri&is differed among the groups. Also body weight (except decreased weight in the last week at the highest doss) and weight of organs (exc~t decreased weigMc4 llverinmaleratsatthehighe~tdoseanddecreasedweightof adreM at the middle doSe)did not ddfer between the groups. Some differencesin biochemical parameterswere not doredependant and irr&vant for toxicity of the substance Histolcgycel examination of different organs caused no regressive changes which would be an evident indicatorof toxic effect.
at about 2W mgikg. Also. is obvious that’che induciion oimic,oscmalenwmes is not thee& factw respons,blstorthe development of polychlorinatedbiphenyls: porphyria:in viw: bpadperoxi-
This study tested the hypothesis lhat a pepide. correeqonding10 thelirst (HXh motif ofphwa. forms a binsrysandwich in the presswe 0‘ trall~ition metal ton lZnz+ and Nb+). Synthetic peptide I-KHRHRHE-I was linked to a resin bead 0, to biotin. Peptic& .-are mixed and mcubated (1 h, 25-C. 10 mM tns, pH 7.4)wilh and withoulZn2+ 0, Niz+. Theassauation 01 both complexes wes assayed by adding the avidin-alkalinephosphatare. After incubation and washing an associated alkaline phorphatase activitywas ana;minun added metal. ihe foil&ing &&s were obtaned: alk&e pbwphatase activity tmsm i SE: umollminA) wm 6.S f 2.0 miny9 Zn2+ VBRUS20.5 I3.9 plus Zn2+ (p < 0 Olland 5.7 f 1 S m,nw Ni2+ versus 12.4 * 2.1 plus N?+ (p c 0 05). Thacalaredcompkxlonedwhenpeptidelinkedtobiotin(l.5mlM~ wee mixed with NiC12solution IO.75 o, 1.5 mM) and studied bv spw tropbotomeby and circula, dichroism. Tiw spectral absorprion bends ,394 (8.1). ,339 (4.2,. 745 12.71, 1060 14.4,) and CD spectra suggest sn octahedral (high spinl binding mwJe oi Ni (111.These resuhe in-
es a result 01 the lack of &vopwhygii in lead ccmamiwatedenvironments. and byingesliondwingsubrdala~empts 01 wetwwiubk kad compounds.
Obj.&&w The am of tha stud” wbj to ealuale the orgam damage in acute lead paiaamngvia inhaktbn h4afer;afandMertrods:Tha clinicalcou,~? ol acute lead poisoningin 3 males zq., 57.40 and 23 yeem was ~rsected Tw of them were exposedto lead steem dwingths unprofess:onaibenew bumme the tn,,d was exposed during the rwxal making. All the poixlned were sem to the Cliwc Imm the augicai depanrrents of rqonal ho$ptals wh,le hosp~bksabonbecause ot colicky abdominal pain. Tha high blmd lead levels1110. 149. 12E ~9961 and Ihe skvated kvals of caproporphyrinand ULA in urinewere found.
Due to evaluation of organs damage the ultraaonograpky of ab dominal catty. ltetic scmtigraphy and hepaiography. brain computer tomography ek?ctracardiagraphy and echocardiography were per. ‘armed. Resulfs: Any Mary eafculOs~swas nottound in ultrasonographic ex. amination. The static scintigraphv welded an abnormal iknage of liver in efl sublti~. Hepatohifiary dynamic %intigraphy Ihepatglraphy) revealed liver function failure of respectively 45%. 30% end 35%. The brain dystrophywas found in Gland neuropsqchological examination. TM retuft5 Of EEG were normel. Al%? the electrocardiography and echocardiographywere within normel limfts. Conclusions: As the result of ecute lead poisoning the injury of the WerandtheCentml ner”0”S s~ternwere found. Nowm~tomsafc.rdiovarcufar ?.vstem disorders &en noted. The bran computer tomography. staCc liver scintigraphy end hcp atography combined with biochemical end loricologicaf analysis al. lows an appropriate assessment of poisoning severity and evaluation of organs damage
In damaged renal tubules small round epithelial cells exfoliante [I). Thw occurrence m urine is a certain relatively specific index of the deqree of fubulotoxicitv. After e~osure to the “referent* direct tubtab t&s (HgCIZ. amphot&icin 31. ihe intensity of tubular epithelial cells in urine in experimentat rate is twenty times higher comment~ng wth day 2 already after a singiwdose administration. With the use of a referent drug inducing tubuloto%icity in e mediated wey (sub lethal doses of cvclosporine A. inducing an intensive idtw of Caz, into the cells of tfw smwth muscles of the vesw4% reeufting in vesoconstriction with subsequent ischeemi2etion of the ktiney as a organ StrOnQly supplied with blood). the increase in spithelial cells excreted in urine is onhr slwfold end ontv after rawated sdminisiratffn. In an indirect tubuIOtonic agent, this b!agna& test appears to be an earlier parameter than the examinatton glucosaminidese. alanine-amirwpepMaee8).
tento
The snails Amphimelenia fwlandti and Planarhwius CWRBUSvv~reexposed to 0.58 end Ns-PCP for 16 days. The pa,ho,ogicaf alterations ware ftrst evidentin the gills of A. holandri treated with 1 mgll N&PCP for 3 day, and 0.53 mgJ Na.PCP for 4 days. Sufxhronic wprsw@resultedin greeter gill damage. Epithalial necrosis and sloughing were massive and the only recognizable gil .WucWre was the chitinoue rod. The digesbve gland. gonads and kidney were also affected. Exteneive damage of these organs was observed after 6 days. Snail I comeus was more resistanL The fint changes in gonad and digestive gland were Bvident after4daysof exposure to 1 mgtl Na-PCPandaher 6 days of e~w?.“re to 0.56 r”g,l Ne-PCP
t ma”
holandri;
planorbarfus
CO,“B”S:
Manaterf~nes are present in fumes liberated dunng sawing and pmcessing of fresh wood end are e potentisl risk forworkere in sawmills. Turpenhnecondsts 01 a mixture of monoterpenes. karena being one of the major eom~nents. Tsrpenea.espaciallyBcarene. may irrftate tfteskin and rnuccu~ membranesand prolonged expasure may result in $llergfccontactdermaritfla w chronic lung function Impairment. Inhaled 3carane et a concantration ot 5ooO mg& caused bronchwrmstriction in isolated. vemilatad and perfwzd giriia pig fu,lgs. lb@ effectwes inhibited bythecyctooxypanaseinhibItordicfofenac(1W yMf andthethromboxanelproslaglandinendopsroxid~~ceptorantbSon~t L870.598 (1 t&I. 3.csrene exposure atso increased the amount of thromboxanein ihe fwfusate from the lungs and in cultured calf pulmonarvanerialendothelialceflrXarenecausedados~related:elease of arach~dcnicacid. Thus. the results obtained in this experimental models may have implications in the understanding of the pathophysiologyof %careneinduced obPtructivepulmananldi~aea in humrms.
Oturinary enzymes {Nacely!-,3-D-
1119cc~H.Ml,ch9..Ma”eR.SackI:‘Armaim.+worh.lDr”gRs..29.~35.1919
11,L. Llstbwn.Fali.*~lipswA. Soye,S
Keywords: “eph,otox,crty; d,agnostk teet
Studyaf C&ular Effectsof Chloramphmkaland ita Matabdlks Cytotoxk,Gmnofoxlc Effect8md Dan-R#ponre RmkUonshlp C. Fafarge-Frayssinet. S. Robbane-Bemat. C. Frayssinet. L. Toucas. J-M Seigneunn. E Decfoitre. UPR 42 IFC F-94.901 Vdfajui~France The vbjective was to mvesugete the C)nOtoxic and genotoxn: effe~(s of Chlaramtihen~caffCAP~ and six metabolilesiNOCAF! DH-CAl? NPAP NAPD, CAt’G and Hid’) in human cells in o&r to p&se the’natur~ of actwe metaholites, determine dose-response relaricnship and rw effects concentrations. compare the sensitivity of 3 target cells. Methods The human cells used were: peripheral blood lymphocytes IPBL). Raillymphoma cells, immortalized RiBM from humanbane marrow. The cyioloxic effect was mesured by inhibition 01 3H th-,midineincwporatbninDNAandthegenotaxiceffecibydetect~pnof DNA single strands breaks bvakstlne elution &sr&%: three CAP metabolitee: NOCAA DHCAP end NPAE prs. sented a cytotox~c effect: no-effect concentration were comprised between 1 x 10-e M end 2 9 x 10-e M. CAP end NAPD were cytotoxic at much higer cwcenlratfon (0.7 x 10-4 MI. CAPG and HAP wre no toxicupto4 x 1OJ M. NO.CAf? DH-CAPand NPhPweretheonly CAP meldMites producing a gel~ltoxa effect. The weffea concentralion was 2 x We M in P9L and Rail cells: it was supar~or to 2 x 10-e M in RiEM cells with were lower suncsptibleto cqtotaxicand genotoxic eflect of NO.CAFI OH-CAP and NPAP than human PBLand Raiicells.
cells
Mom”, P.Rymdl A,R~spiratmn.
Keywords: Xarene: lung; thmmboxane; bionchoconstrfctian
S&cllronlcTonknyOf SUB
I.& m29
A. LevriC’ D. Tibaut’. K. Culiakz, M. Nsmec3.
’
RbDB,amedical DepbLek’d d Uublana, Shwenie: 2 Dept of f?3fho&,! Univ of Zagreb, Croat%;3 Dept. of&chsmiro: Unl~. ofLjubf,liana.Sfwenia In sxprimeni ot the 30 daw subchmnlc toxicityof ths substance Lek 8828. a new potemial amipsychatic 111.eighty rats of both sexes divided into 4 groups were used. The first grwp wee treated WMhM.0. the second with 159. and the third wth 5.0 malkaldav substance lek 8929 orally. while to the fourth group 1 mlfiglday dtstilled weter wee given. The msults showad that the male and female rats in all amum survived. Neither clinical svmptcmatolow. nor food CODSURID bon.‘nor haematological examine&a% and uri&is differed among the groups. Also body weight (except decreased weight in the last week at the highest doss) and weight of organs (exc~t decreased weigMc4 llverinmaleratsatthehighe~tdoseanddecreasedweightof adreM at the middle doSe)did not ddfer between the groups. Some differencesin biochemical parameterswere not doredependant and irr&vant for toxicity of the substance Histolcgycel examination of different organs caused no regressive changes which would be an evident indicatorof toxic effect.