pmc logo imageJournal ListSearchpmc logo image
Logo of brjindmedJournal URL: redirect3.cgi?&&auth=0n3iXq5PhWPfTTfuS7mShHHAEwkJHm1LZ7eXzQ5_o&reftype=publisher&artid=1008057&article-id=1008057&iid=103370&issue-id=103370&jid=173&journal-id=173&FROM=Article|Banner&TO=Publisher|Other|N%2FA&rendering-type=normal&&http://www.pubmedcentral.nih.gov/tocrender.fcgi?journal=172&action=archive
Br J Ind Med. 1975 August; 32(3): 181–192.
PMCID: PMC1008057
Comparison of in vivo effect of inorganic lead and cadmium on glutathione reductase system and delta-aminolevulinate dehydratase in human erythrocytes.
H A Roels, J P Buchet, R R Lauwerys, and J Sonnet
Abstract
The activity of delta-aminolevulinate dehydratase (ALAD) of erythrocytes, the lead (Pb-B) and cadmium (Cd-B) concentration in whole blood, the content of reduced glutathion (GSH) in erythrocytes, and the regeneration rate of GSH by intact erythrocytes were measured during an epidemiological survey of 84 men employed in a Belgian cadmium and lead producing plant. A control group of 26 persons (students and laboratory staff) was also examined. The logarithm of the ALAD activity is highly inversely correlated with log Pb-B (r = -0.760) but no correlation was found with log Cd-B. There exists a significant negative correlation between GSH and log Pb-B (r = -0.423) but not between GSH AND LOG Cd-B. The apparently good relationship between log ALAD and GSH disappeared completely by holding log Pb-B constant, but log ALAD remained highly inversely correlated with log Pb-B when standardized for GSH concentration (r = -0.748). In vivo investigation of the GSH regeneration rate of intact erythrocytes demonstrated clearly that the overall activity of the glutathione oxidation-reduction pathways is not impaired in Pb and Cd-exposed workers with significantly increased Pb-B and Cd-B, since their initial GSH regeneration rate (first 15 minutes) was identical with that of the control group. Results of similar in vitro experiments in which control whole blood was incubated before-hand with Pb2+ or Cd2+, or both, reinforce this conclusion. Since increased Cd-B and Pb-B do not influence the glutathione reductase system of erythrocytes, and since endogenous erythrocyte GSH is not correlated with Cd-B, the moderate decrease in endogenous erythrocyte Gsh found in Pb-exposed workers might result from a Pb-induced impairment for the erythrocyte mechanism for glutathione synthesis.
Full text
Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.9M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
  • Barltrop, D; Smith, A. Interaction of lead with erythrocytes. Experientia. 1971 Jan 15;27(1):92–93. [PubMed]
  • Basecqz, JM; Lauwerys, R; Buchet, JP. Etude comparative de divers tests biologiques d'exposition au plomb. Arch Mal Prof. 1971 Jun;32(6):453–463. [PubMed]
  • Batolska, A; Marinova, H. Modifications du glutathion chez les travailleurs d'une entreprise métallurgique minière. Arch Mal Prof. 1970 Mar;31(3):117–122. [PubMed]
  • BEUTLER, E; DURON, O; KELLY, BM. Improved method for the determination of blood glutathione. J Lab Clin Med. 1963 May;61:882–888. [PubMed]
  • BEUTLER, E; ROBSON, M; BUTTENWIESER, E. The mechanism of glutathione destruction and protection in drug-sensitive and non-sensitive erythrocytes; in vitro studies. J Clin Invest. 1957 Apr;36(4):617–628. [PubMed]
  • Bruenger, FW; Stevens, W; Stover, BJ. The association of 210Pb with constituents of erythrocytes. Health Phys. 1973 Jul;25(1):37–42. [PubMed]
  • CARLSON, LA; FRIBERG, L. The distribution of cadmium in blood after repeated exposure. Scand J Clin Lab Invest. 1957;9(1):67–70. [PubMed]
  • Cartasegna, C; Vergnano, C; Ardoino, V. Livelli di glutatione ridotto e attività ALA-deidratasica nel sangue e nel fegato dopo trattamento con N-etil-meleimide. Boll Soc Ital Biol Sper. 1967 Sep 30;43(18):1209–1210. [PubMed]
  • Chisolm, JJ., Jr Lead poisoning. Sci Am. 1971 Feb;224(2):15–23. [PubMed]
  • Colucci, AV; Hammer, DI; Williams, ME; Hinners, TA; Pinkerton, C; Kent, JL; Love, GJ. Pollutant burdens and biological response. Arch Environ Health. 1973 Sep;27(3):151–154. [PubMed]
  • De Barreiro, OL. 5-aminolaevulinate hydro-lyase from yeast. Isolation and purification. Biochim Biophys Acta. 1967 Jul 11;139(2):479–486. [PubMed]
  • DOORNBOS, DA; FABER, JS. STUDIES ON METAL COMPLEXES OF DRUGS; D-PENICILLAMINE AND N-ACETYL-D-PENICILLAMINE. Pharm Weekbl. 1964 Mar 20;99:289–309. [PubMed]
  • Erich, C; Waller, HD. Zum Verhalten von SH-Verbindungen in Erythrocyten nach in vivo-Vergiftung mit Schwermetallen und Arsen. Klin Wochenschr. 1967 Oct 1;45(19):983–986. [PubMed]
  • Gibson, SL; Goldberg, A. Defects in haem synthesis in mammalian tissues in experimental lead poisoning and experimental porphyria. Clin Sci. 1970 Jan;38(1):63–72. [PubMed]
  • GRANICK, S; MAUZERALL, D. Pbrphyrin biosynthesis in erythrocytes. II. Enzymes converting gamma-aminolevulinic acid to coproporphyrinogen. J Biol Chem. 1958 Jun;232(2):1119–1140. [PubMed]
  • Granick, JL; Sassa, S; Granick, S; Levere, RD; Kappas, A. Studies in lead poisoning. II. Correlation between the ratio of activated to inactivated delta-aminolevulinic acid dehydratase of whole blood and the blood lead level. Biochem Med. 1973 Aug;8(1):149–159. [PubMed]
  • Ganzoni, A; Rhomberg, F. Hämolytische Krise bei Mangel an Glukose-6-Phosphat-dehydrogenase und Bleiintoxikation. Acta Haematol. 1965 Dec;34(6):338–346. [PubMed]
  • Hapke, HJ; Prigge, E. Interactions of lead and glutathione with delta-aminolevulinic acid dehydratase. Arch Toxikol. 1973;31(2):153–161. [PubMed]
  • Hernberg, S; Nurminen, M; Hasan, J. Oxygen and glucose consumption and lactate production of erythrocytes of workers exposed to inorganic lead. Int Arch Arbeitsmed. 1967;23(2):117–126. [PubMed]
  • Hernberg, S; Tola, S; Nikkanen, J; Valkonen, S. Erythrocyte delta-aminolevulinic acid dehydratase in new lead exposure: a longitudinal study. Arch Environ Health. 1972 Aug;25(2):109–113. [PubMed]
  • Icén, A. Glutathione reductase of human erythrocytes. Purification and properties. Scand J Clin Lab Invest Suppl. 1967;96:1–67. [PubMed]
  • Jacob, HS; Brain, MC; Dacie, JV. Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital Heinz body hemolytic anemia. J Clin Invest. 1968 Dec;47(12):2664–2677. [PubMed]
  • JACOB, HS; JANDL, JH. Effects of sulfhydryl inhibition on red blood cells. I. Mechanism of hemolysis. J Clin Invest. 1962 Apr;41:779–792. [PubMed]
  • JONDERKO, G. [Diagnostic value of the determination of the blood glutathione level in chronic lead poisoning in human subjects.]. Pol Arch Med Wewn. 1961;31:647–655. [PubMed]
  • Kao, RL; Forbes, RM. Effects of lead on heme-synthesizing enzymes and urinary -aminolevulinic acid in the rat. Proc Soc Exp Biol Med. 1973 May;143(1):234–237. [PubMed]
  • Lauwerys, RR; Buchet, JP. Occupational exposure to mercury vapors and biological action. Arch Environ Health. 1973 Aug;27(2):65–68. [PubMed]
  • Lauwerys, RR; Buchet, JP; Roels, HA. Comparative study of effect of inorganic lead and cadmium on blood delta-aminolevulinate dehydratase in man. Br J Ind Med. 1973 Oct;30(4):359–364. [PubMed]
  • Lauwerys, R; Buchet, JP; Roels, HA; Materne, D. Relationship between urinary delta-aminolevulinic acid excretion and the inhibition of red cell delta-aminolevulinate dehydratase by lead. Clin Toxicol. 1974;7(4):383–388. [PubMed]
  • LENZ, GR; MARTELL, AE. METAL CHELATES OF SOME SULFUR-CONTAINING AMINO ACIDS. Biochemistry. 1964 Jun;3:745–750. [PubMed]
  • LICHTMAN, HC; FELDMAN, F. In vitro pyrrole and porphyrin synthesis in lead poisoning and iron deficiency. J Clin Invest. 1963 Jun;42:830–839. [PubMed]
  • Majerus, PW; Brauner, MJ; Smith, MB; Minnich, V. Glutathione synthesis in human erythrocytes. II. Purification and properties of the enzymes of glutathione biosynthesis. J Clin Invest. 1971 Aug;50(8):1637–1643. [PubMed]
  • McIntire, MS; Angle, CR. Air lead: relation to lead in blood of black school children deficient in glucose-6-phosphate dehydrogenase. Science. 1972 Aug 11;177(48):520–522. [PubMed]
  • Millar, JA; Battistini, V; Cumming, RL; Carswell, F; Goldberg, A. Lead and delta-aminolaevulinic acid dehydratase levels in mentally retarded children and in lead-poisoned suckling rats. Lancet. 1970 Oct 3;2(7675):695–698. [PubMed]
  • Moore, MR; Beattie, AD; Thompson, GG; Goldberg, A. Depression of delta-aminolaevulic acid dehydrase activity by ethanol in man and rat. Clin Sci. 1971 Jan;40(1):81–88. [PubMed]
  • Nakao, K; Wada, O; Yano, Y. Delta-aminolevulinic acid dehydratase activity in erythrocytes for the evaluation of lead poisoning. Clin Chim Acta. 1968 Feb;19(2):319–325. [PubMed]
  • PIHL, A; ELDJARN, L; BREMER, J. On the mode of action of x-ray protective agents. III. The enzymatic reduction of disulfides. J Biol Chem. 1957 Jul;227(1):339–345. [PubMed]
  • Roels, HA; Buchet, JP; Lauwerys, RR. Inhibition of human erythrocyte delta-aminolevulinate dehydratase by lead. In vitro artifact or real phenomenon in vivo? Int Arch Arbeitsmed. 1974;33(4):277–284. [PubMed]
  • Rogers, LE; Battles, ND; Reimold, EW; Sartain, P. Erythrocyte enzymes in experimental lead poisoning. Arch Toxikol. 1971;28(3):202–207. [PubMed]
  • RUBINO, GF; COSCIA, GC; PERRELLI, G; PARIGI, A. [Behavior of glutathione, the glutathione stability test and glucose-6-phosphate dehydrogenase activity in lead poisoning.]. Minerva Med. 1963 Apr 4;54:930–932. [PubMed]
  • Saita, G; Lussana, S. Intossicazione da piombo in portatrice di emazie fabiche. Med Lav. 1971 Jan;62(1):22–27. [PubMed]
  • SCOTT, EM; DUNCAN, IW; EKSTRAND, V. PURIFICATION AND PROPERTIES OF GLUTATHIONE REDUCTASE OF HUMAN ERYTHROCYTES. J Biol Chem. 1963 Dec;238:3928–3933. [PubMed]
  • Secchi, GC; Alessio, L; Cambiaghi, G. Na plus-K plus-ATPase activity of erythrocyte membranes: in urban populations not occupationally exposed to lead. Arch Environ Health. 1973 Dec;27(6):399–400. [PubMed]
  • Secchi, GC; Erba, L; Cambiaghi, G. Delta-aminolevulinic acid dehydratase activity of erythrocytes and liver tissue in man: relationship to lead exposure. Arch Environ Health. 1974 Mar;28(3):130–132. [PubMed]
  • Srivastava, SK; Beutler, E. Permeability of normal and glucose-6-phosphate dehydrogenase deficient erythrocytes to glutathione. Biochem Biophys Res Commun. 1967 Sep 7;28(5):659–664. [PubMed]
  • Tietze, F. Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: applications to mammalian blood and other tissues. Anal Biochem. 1969 Mar;27(3):502–522. [PubMed]
  • Tomio, JM; Tuzman, V; Grinstein, M. Delta-aminolevulinate dehydratase from rat Harderian gland. Purification and properties. Eur J Biochem. 1968 Oct 17;6(1):84–87. [PubMed]
  • Vens, MD; Lauwerys, R. Détermination simultanée du plomb et du cadmium dans le sang et l'urine par le couplage des techniques de chromatographie sur résine échangeuse d'ions et de spectrophotométrie d'absorption atomique. Arch Mal Prof. 1972 Mar;23(3):97–105. [PubMed]
  • Vergnano, C; Cartasegna, C; Bonsignore, D. Livelli di glutatione ridotto nella intossicazione sperimentale da piombo. Boll Soc Ital Biol Sper. 1967 Sep 15;43(17):1099–1102. [PubMed]
  • Waldron, HA. The anaemia of lead poisoning: a review. Br J Ind Med. 1966 Apr;23(2):83–100. [PubMed]
  • Wilson, EL; Burger, PE; Dowdle, EB. Beef-liver 5-aminolevulinic acid dehydratase. Purification and properties. Eur J Biochem. 1972 Sep 25;29(3):563–571. [PubMed]
  • Yawata, Y; Tanaka, KR. Studies on glutathione reductase and regeneration of reduced glutathione in normal human adult and cord red cells. Clin Chim Acta. 1973 Jul 14;46(3):267–275. [PubMed]