Experimental Lead Poisoning and Intestinal Transport of Glucose, Amino Acids, and Sodium

P e d i n t . Res. 11: 153-157 (1977)

A'TPase glucosc intestinal a b s o r p t i o n

lead poisoning soclii~~il

Experimental Lead Poisoning and Intestinal Transport of Glucose, Amino Acids, and Sodium R A U L A. WAPNIR."ll RAhlON A. EXENI, hlELlNDA hlCVICAR. A N D FlhlA LIFSHITZ Riorllr .s/lorc, I / l r i ~ ~ ~ ~ rHo.sl~itrr/. .sily t)cpcrrlttrc,trl o f /'c3t/icllric.s, ~\frrtr/rrrs.sc~f, crtrtl C'or~rc,//Utrii8c,r.si!y,\lcc/ic.o/ CoIIc>gc,, N c ~ t );)rk. , New. Y o r k . U S A n ~ ~ p c r r / ~ ~orfc ,Pc~licrtric~.~. ~rt

Sur~~r~~ary

inl: - o n the ilietarv st:~tuso f the animals (5, 19. 22, 50. 5 1 ) . rl'l~is nloclcl, ho\vever. proviclcs tlie closest similarity to tlie conseJ u v e ~ ~ i lrats e fecl a cliet c o ~ ~ t a i ~1 % ~ ileacl ~ ~ g:~cctate for 7 ~ ~ L I ~ I of I C"pica" ~ S i r l chil~lrcn(26, 42. 47. 52). 71'lie rclatioriship weeks, in acltlition to an i1111)aireclgrorrth rate ant1 renal fu~ictior~ bct\vccn adciluacy of ilict ancl the esterit of le;~cl poisoning c l c r a r ~ g e ~ ~ ~ es~llTerecl nts, 111a1al)sorplion of glncose ar~clcertain damage has been invcstigatccl in cspcrimcntal studies ( 5 , 2 2 . 50) Tl~e a ~ n i acicls, ~ ~ o as asscssecl by all ill 1.i1'o perfusion tcch~~iclue. and in nutritional surveys of chilclren (6, 38). recluetion in glucose al~sorptionr a ~ ~ g eI)et\r.eer~ tl 1 0 % ancl 3 1 % The p~rrposcof this stilcly was to tlctcrminc the cffccts of a w l ~ e nthe carbol~yclraten a s p u ~ ~ ~ pin e ccl o r ~ c e ~ ~ t r a t iof o ~ 2-80 ts chronic intake of Icail on the intestinal transport of glucosc. r ~ ~ hTl l. ~ i sa l t e r a t i o ~was ~ cor~~patible wit11 a n o n c o ~ ~ ~ p c t i ttype ive amino acicls. oncl soclium. and the possibility of cellular ariil/or of transport i n h i l ~ i t i o ~.l'lie ~ . intesti~~al al)sorption of glycir~c, physiologic damage to the intestinal rnucosa. in aclclitiorl to thc Iysine, and phel~ylalal~ir~e were, respcctivcly, clecrcasctl 22, 18, prcvioi~slyilcscrihccl impaircil gro\vtli rate and multiple renal ancl 1570 \ \ \ I I ~ I tl~ese I a111i11oocicls a c r e prcser~tat I r ~ ~ levels. hl function clerarige~~lcnts. S o c l i u ~trans~)ort ~~ was severclv rcclucccl (57.6 & 17.9 (SEhI) vs. 124.2 & 1 7 . i pEcl/n~in.~111)' ar~clilltcstillal Illucosa ( ~ a + - k + ) A'I'Pase was concor~iit:~r~tly lower ill t l ~ eIcatl-i~~tosicotccl rats II~ Ilo~v(186.4 & 19.0 vs 268.4 2 29.8 IIIIIOI P / I I I ~ I I . Iprotein). hlale Wistar rats. \veighing 60-80 g, in groups of four to eight. ever, this enzyllle tras not alterecl in liver ar~clkiclncy. Further- ~veregiver] ( i d l i l ~ i ~ ~:I i cor~iplcte t~t ilict (56). eor~t;iir~irig I 76 1e;icI ic Illore, i ~ ~ t e s t itllucosa ~ ~ a l fructose- I ,(,-clipl~osphatase,s u c c i ~ ~clc. acetate plus free access to water, for :I pcriocl of 7 ~ \ c e k s ~I'lie hyclroge~~ase, pyruvatc kinase, ancl tryptopl~anI~yclrosjlasewere effectivc lead intake was cstinlated to be 600 pg/!ig/tl:iy. I>~~ririg 1101 clilTerc~~t in c s p e r i ~ ~ ~ c nand t a l c o ~ ~ t rao~l ~ i r ~ ~T al ~l es s. cstuclies the last ivcck of the esperinients. urine collections were carriccl substar~tiatethe presellcc of functional ar~clbiocl~cn~ical a l ~ l ~ o r -out over several 34-11s periocls. The esperimental :inilnals were 111a1itic.sin the i r ~ i e s t i ~Illucosa ~al of jourlg rats w11e11fecl sul)stan- liousccl in metabolic cages ancl food irltake \vas mei~sureilcl:~ily. tial a n ~ o u n t sof a soluble leacl salt. It is, therefore, reasonal)le to Urinary glucosc \vas ilctcrminccl hy a glucose oxiclase rnetliod accept t l ~ cpossil)ility that pl~ysiologieclau~ageoccurs in tiss~res (58). Arnino acid nitrogen (23). inorganic phosphate (I 8). aricl clircctly s~tl)jccteclto l ~ i g ancl l ~ persistent levels of a tosic agent, creatirline rlitrogerl (9) \vcrc :lssayed by colorimetric proceclures. as it occurs in other organs, u~~clerscoring the parallclist~~ be- Atomic iibsorption tecliniilucs (Perkin-Elmer, moilcl 305A t t r c c l ~trillsport I I I ~ ~ ~ I ~ I I ~atS Ithe I I Srenal a~lcli ~ ~ t c s t ilevels. ~~al (59)) were appliecl for Icacl (32). calcium. ancl nlagncsium clctermini~tions(3) ant1 flame pliotornetsy for sodium ;irlcl potazsi~~m assays (60). 'I'he g a s t r o i ~ ~ t e s t i ~ s y~ ra ~l ~ p t ooften ~ ~ t s associated nit11 c l ~ r o ~ ~ i cTile intestinal i~bsorptionof glucose. amino acicls. ancl clcctrol g itr ~ * i ~proceclurc *o (55. 50). of the Iytes was stucliccl in the rats ~ ~ s i lan lcacl i ~ ~ t o s i e a t i omay n 11e related to physiologic clal~~agc in concentrations of 2 to SO mhl, lahelecl \vith " C in ~ I I I ~ C ~ I ~ I I ~ S I ITherefore, IS. i ~ ~ t e s t i ~ Glucose, ~al i r ~ t e s t i ~ ~I IaI lU ~ O Stra11~11ort Illocosa coultl be consiclerecl a n o t l ~ e rprit~iarytarget organ for tracer ornounts, plus 1 mhl sirlglc L-amino acids. includirig :'H lead p o i s o ~ ~ i n gas, the kiclr~ey,the erytlirol~oieticsyste~n,ant1 tracer, i l l hot11 c;rscs at a level about 50.000 dpm/ml, \vcre aclclecl to Krebs-Ilcnsclcit bicarbonate buffers. Lahclcd mct:~bolitcs nervous tissue are l i ~ ~ o \ to % nbe. \vere purchasccl frorn Nc\v Engl:~rlcl Nuclear (61). l'he tonicity \vas m:~intaincil by ailjusting the conccntr;rtion of N ~ I C I .All Lcacl intosication in humans has been sho\\n to affect the chemicals \Yere obtaineel from Fisher Scientific Co. (62). Polycentral nervous system. the liem:~topoieticsystem, ancl the kicl- cthylerle glycol (PEG), mol \vt 3.000-3.700, C:~rbo\vax4000 ( J . ncys (17, 13. 16. 25). Susceptibility of reel blood cell mcmhranc T . Baker Co. ((13)). 6.0 g/litcr, served as :I nonabsorbable (Nil +-K+)-A'l'l'ascto lead poisoning 11~1sheen shown in ~vorkcrs rnarkcr ancl the ratio of its concentration (35) in the buffer to suffering tlie consccluenccs of escessivc exposure to this agent that of the pcrfusatcs was used as :I correction factor for the (27). The Icacl hurcleri in chililrcn is the highest among those calcul;~tionof absorption rates. The perfusing liiluicls \vcrc hubliving in urharl ghettos. p:~rticularly if they chronically ingest bled with O,:CO,, 95:5 (Liquid C:~rboriic(64)). anil maintained small amounts of \vall peelings covereel with lead-containirig at 37" cluring the espcrirncnts. In brief. the animals \\.ere antspaint (6). 71'his hits been c:illecl "a prevcntahlc childhoocl cliscasc thetizcd \\,it11 1 .2 g/kg urethane given intraperitonc;illy. The of the slums" (42). abdominal cavity was openecl by a micllirle incision ancl thc srn:~ll Nunicrous investigators h:r\,c usccl rats as an animal moclcl of intestine cnnnulated helo\\, the lig;imcnt of Treitz. A 20 cm-long leacl intoxication. tluplic:~ting;~ltcr:rtionsin kiclncy tubules (24); jejunal scgnient was utilized anel the intestinal contents \\,ashcd changes in growth. bcl~:~vior, and catecholamines (21); 1~r:iin out wit11 t\vo 10-ml portions of warm 0.15 hl NaCI. 'l'hc prosimetabolism (43, 48); and damage to the licrnatopoictic mccha- ma1 junction W;IS ; I ~ ~ ; I C I I ~ CtoI a peristaltic pump (Iinrvnril Appanisnls (37. 39). 'I'hc oral :iclrllinistratior~ of lead salts hiis been r i ~ t ~(65)) ~ s :IIILI perfusccl :it a rate of 0.70-0.23 ml/min. The clloscn in most sttldics, in spite of variable rates of :~t>sorption, concentration of tlie glucose o r amino acids was rlctermined by estim;~teclhettvccn 2 76 ;illil 1 0 % of the i~igcstecldose. clcpcrld- isotope clilution computation after counting aliilllots in :I licluicl

'l'ablc I . Urit~rrr:,~ c,.\-c~rc,!iotrof iltrrir~rt.srrrc~rrholitc~.~ it1 I~~rrtl-~~oi.sotrc.tl rrrts (l'h)

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ISxpcri~iient;ilgroups -

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Colitrol .

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p p p p

Urine volutiic (1111174lir) l.c;itl (pd2-4 l ~ r ) Ciluco\e (mg/24 lir) AAN/crc;~ti~iN i~~c C;i/crcati~ii~ie N hlgIcrc;itini~lcN I1/crc;~tinincN Sotliu~n(pllil/24 hr) I'ot;is\iu~li (pli11I24 hr)

10.5 ? 105.8 ? 10.67 t O.86 ? I .Ol ? 25.1 2 1.10 t 004 ? I ,005 t

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I .3 (34)

4.7

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33.6 (55) l .07 (23) 0.00 (22) 0.24 (22) 10.3 (21) 0.38 (21) 70 (38) I03 (35)

0.3

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3.38 ? 0.53 ? 0.(10 ? 64.1 -t 2.40 ? 1.255 ? 7.005 ?

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p p p -

0 . 8 (20) 1.2 (23) 0.78 (13) 0.04 (14) 0.15 (13) 13.8 (14) 0.70 (14) 100 ( 10) 700 ( I 1 )

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