Pergamon Presa

Life Sciences Vol . 20, pp . 1715-1722, 1977 . Printed in the II .S .A .

EFFECTS OF ENVIROTJMENTAL LEAD LEVELS ON THE URINARY KALLIKREIN EXCRETIOTi OF EXPOSED WORKERS Paolo Boscolo, Enrico Salimei,

Annamaria Adamo

and Giovanni Porcelli Istituti di Medicina del Lavoro e di Chimica dell'Università Cattclica di Roma Centro .di Chimica Recettari del C .N .R ., E .N .? .I . Via Pineta Sacchetti 526,

I-00168 Roma, Italy

(Received in final form April 20, 1977)

Summary Ten men, working in a factory making car batteries, were hospitalized in order tc establish the diagnosis of lead intoxication . The urinary kallikrein activity, determined in their 24-hr urinea, was found to be lower than that of a control group . Kallikrein activity was then determined in morning urines of another group of 25 lead exposed men working in the same factory . The urines of this group were collected before and after some environmental improvements which reduced lead concentration in the factory ambient air . The urinary kallikrein excretion oP exposed workers was very law before environmental improvements . After the lead reduction in the environmental air, the urinary kallikrein excretion of the same workers was significantly increased ; nevertheless, it remained still lower than the control group . It has been demcnstrated that lead induces alterations in kidney enzymes (1) either by inhibiting their activity (2) or by modifying their synthesis (3) . Ultrastructural studies on the kidney of lead poisoned animals and persons have also demonstrated the presence of intranuclear inclusion bodies (4,5) and of mitochondrial alterations (4,6) . Despite these experimental results, there is considerable controversy about the effects of lead on kidney and on the vascular system (7,8,9) . Support for the view that lead exposure may be correlated with degenerative vascular diseases, 'is found in a British study of battery workers (7) . In another study of Cramér and Dahlberg (8) there is support for the view that lead workers in carefully 1715

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supervised plants do not have a higher risk cf hypertension than the unexposed population . Plevertheless, it seems possible that lead exposed workers may develop hypertension and renal function impairment under ccnditions nct clearly defined (9) . The endocrinclogical alterations of lead-induced hypertension have not, ~intill now, been studied . Sandstead et al . observed, however, in nine lead intoxicated patients (only one of them hypertensive) a decrease of the plasma renin activity and of the aldostercne secretion rate (10) . It has been demonstrated that urinary kallikrein excretion is decreased in essential hypertensive patients (11,12,13) and in strains of hypertensive rats (14) . Urinary kallikrein is an enzyme which releases bradykinin, a potent vasodilatator polypeptide, from an alpha2-globulin called kininogen (15) . The kallikrein excreted in the urine appears tc be synthetized in the kidney (16,17), and a correlation between the synthesis cf the enzyme in the kidney and its excretion in the urine has also been demonstrated (18) . Since hypertension induced by lead may not depend on an increase of a vasopressor substance, such ~as renin, it seemed tc us worthwhile tc study the question of whether it could depend cn the reduction cf vasodilatator substances such as orostglandins (19) or kallikrein . After a preliminary study on the urinary kallikrein excretion on lead poisoned rabbits (20) and on a small group cf men occupationally exposed to lead (20), we decided tc investigate the effect cf environmental lead exposure cn the kallikrein excretion in men working in a factory making car-batteries . Subjects and Methods From 1972 tc 1974 ten lead exposed men, working in a factory making car-batteries, were hospitalized at the Institute of Occupational Pdedicine of the Catholic University of Rome to establish the diagnosis of lead intoxication . When the men were hospi talized their average age was 30 (ranging from 19 to 38 years) and their average length cf lead exposure was 20 months (ranging from 9 months to 3 years) . Clinical examination of workers showed no symptoms of poisoning . In order tc evaluate lead exposure, 24-hr urines were collected before and during versenate treatment (1 .5 g Ca-EDTA in 500 ml of 5°~ glucose solution each day for 3 days) . Urinary kallikrein activity was determined with the method of Porcelli and Croxatto (21) using benzoylarginine-ethylester (BAEE) as substrate . The 24-hr kallikrein activity (21), delta-aminolevulinic acid (ALA) (22) and lead (23) urinary levels of these 10 patients were compared with those determined in the 24-hr urines of a first control group of 22 healthy men of similar age, occupationally not exposed to lead, living in the suburbs of Rome . Since the 10 workers we hospitalized were heavily exposed to

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IIriaary Rsllikrein and Lead Exposure

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lead, corrective measures were taken (from March 1974 to September 1975) in their factory in order to improve the air quality of some The distribution of lead in the ambient air of working areas . the factory was not uniform, but the workers were frequently rotated through various working positions, thus receiving a more uniform exposure . Morning urines oP 25 men employed in the factory were collected in 1Qarch 1974 . Morning urines of the same workers were then collected in September 1975 . When the men were examined (in September 1975) their average age was 32 (ranging from 22 to 45 years) and their average length of lead exposure was 3 years (ranging from 2 to 8 years) . Most cf them were in good health, a Pew suffered from gastritis, only one had been hypertensioe some months before . Kallikrein activity, ALA, lead and creatinine levels of mcrning urines of these 25 exposed workers were compared with those determined in mcrning urines of a second control group cf 25 men (not included in the first ccntral group of 22 men) of similar age, occupationally not exposed to lead, living in the suburbs of Rome . Although the samples were randomly selected, none of controls had suffered frcm hypertension . The creatinine levels determined in morning urines of both control and exposed groups presented no statistical differences . The values (Mean _+ S .E .M .) cf urinary creatinine of the control group were 1 .55 _+ 0 .07 g/1, and these of the exposed group were 1 .63 _+ O .OB g/1 in March 1974 and 1 .52 _+ 0 .08 g/1 in September 1975 . Although we did not complete the study, the urinary kallikrein activity of control subjects seemed to be higher in urines obtained in the morning than in the urines collected during cther times of the day, acccrding to a previous investigation (24) . The statistical evaluation of data was made by the Student "t" test and by the matched pair "t" test . Results The urinary kallikrein activity, determined in the 24-hr urines of the 10 hospitalized workers, was significantly lower than that of the control group . The urinary ALA and lead of the lead exposed patients were also altered (table I) . Although envircnmental improvements were executed only in scme working areas of the factory, factory workers seemed to be less expcsed to lead in September 1975 than in March 1974 (table II) . Kallikrein activity cf the mcrning urinary samples, collected frcm lead expcsed persons in March 1974 was very lcw compared tc the control group . A significant alteraticn was also present in the samples of September 1975 . Plevertheless, in the

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TABLE I Kallikrein . ALA and lead in 24-hr urine of lead exncsed workers ?tallikrein (units/24-hr)

ALA (mg/24-hr)

Lead(ug/24-hr) Before Maximum* EDTA ~ur in¢ EDTA

Control (22)

25 .1 + 1 .7

3 .0 + 0 .2

29 + 4

Exocsed (10)

15 .4 + 4 .2

5 .8 + 0 .7

149 + 13

Student "t" test

p< 0 .05

p< 0 .001

1842 + 126

p< 0 .001

The results given are means _+ S .E .M . * According to Teisinger and Srbcvà (25) subjects not exposed to lead, after a single intravenous injection of 2 .8 .q cf Ca-EDTA, excrete in their 24-hr urinea from 58 to 352 }~g cf lead . same subjects, the alteration cf urinary kallikrein excretion, after the environmental improvements, "was reduced (table III) . Urinary ALA was significantly elevated in the lead exposed grciip in bath samples of March 1974 and September 1975 . Pip significant decrease of ALA was cbserved in the urines cf the same exposed workers in September 1975 in ccmparison with the samples cf March 1974 . On the ccntr.ary, although not all cf the urines were analyzed for lead, it was observed that exposed workers showed higher levels of urinary Pb in March 1974 than in September 1975 . TABLE II Lead ccncentratian in the air cf the factcry making car-batteries befcre and after thg environmental i~ rovements were completed Sampling positicn

47orking place rang of Pb levels (ug/m ) September 1975 March 1974

Foundry

13 - 504

32 - 224

Spreading of plates

83 -

30 -

Welding

48 - 107

14 - 161

Assembling

41 - 101

19 -

90

59

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Urinary Kallikrein and Lead Exposure

Vol . 20, No . 10, 1977

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TABLE III Kallikrein, ALA and lead in morning urine of lead exposed wcrkers before and after environmental imprcvements were completed Groups

Kallikrein (un its/1 )-

1 . Control (25)

29 .9 + 3 .5

3 .2 + 0 .2

24 + 4 (12)

2 . Exposed ( 25) (March 1974)

10 .2 _+ 1 .9

5 .3 _+ 0 .4

106 _+ 21 (8)

3 . Exposed (25) (September 1975)

17 .7 _+ 3 .5

4 .4 _+ 0 .2

63 _+ 9 (12)

Groups

Kallikrein

ALA

1 vs 2

p < 0 .001

p < 0 .001

p < 0 .001

1 vs 3

p

Effects of environmental lead levels on the urinary kallikrein excretion of exposed workers.

Pergamon Presa Life Sciences Vol . 20, pp . 1715-1722, 1977 . Printed in the II .S .A . EFFECTS OF ENVIROTJMENTAL LEAD LEVELS ON THE URINARY KALLIKR...
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