title: Pyruvate kinase activity and δ-aminolevulinic acid dehydratase activity as biomarkers of toxicity in workers exposed to lead.
abstract: Lead (Pb(2+)) is a heavy metal that has long been used by humans for a wide range of technological purposes, which is the main reason for its current widespread distribution. Pb(2+) is thought to enter erythrocytes through anion exchange and to remain in the cell by binding to thiol groups. Pyruvate kinase (PK) is a thiol-containing enzyme that plays a key role in erythrocyte cellular energy homeostasis. δ-aminolevulinic acid dehydratase (δ-ALAD) is the second enzyme in the heme biosynthetic pathway and plays a role in the pathogenesis of Pb poisoning. Our primary objective was to investigate the effect of Pb(2+) on the activity of the thiolenzymes δ-ALAD and PK and on the concentration of glutathione (GSH), a nonenzymatic antioxidant defense, in erythrocytes from Pb-exposed workers. The study sample comprised 22 male Pb workers and 21 normal volunteers (15 men and 6 women). The Pb-exposed workers were employed in manufacturing and recycling of automotive batteries. Basic red-cell parameters were assayed and total white blood cell counts performed. PK and δ-ALAD activity and blood Pb (BPb) concentrations were determined in all subjects. Pb-exposed individuals had significantly greater BPb levels than controls. Both PK and δ-ALAD activity levels were significantly lower in Pb-exposed individuals than in controls. Pb significantly inhibited PK and δ-ALAD activity in a dose-dependent manner. We found that erythrocyte GSH levels were lower in Pb-exposed individuals than normal volunteers. Pb-exposed individuals had lower values than controls for several red cell parameters (hemoglobin, hematocrit, red blood cell count, mean corpuscular volume). These results suggest that Pb inhibits δ-ALAD and PK activity by interacting with their thiol groups. It is therefore possible that Pb disrupts energy homeostasis and may be linked with decreased glucose metabolism because it affects the heme synthesis pathway in erythrocytes, contributing to the cell dysfunction observed in these in Pb-exposed individuals. These results indicate an apparent dose-effect relationship between PK activity and BPb. PK activity in human erythrocytes can be used for biological monitoring of Pb exposure. Study of the mechanisms by which Pb acts may contribute to greater understanding of the symptoms caused by Pb.
authors.affiliation: Instituto de Ciências da Saúde, Grupo de Pesquisa em Bioanálise, Universidade Feevale, RS 239, 2755, Novo Hamburgo, RS CEP 93352-000, Brazil. lucianef@feevale.br
authors.forename: Luciane Rosa
authors.initials: LR
authors.lastname: Feksa
authors.forename: Evandro
authors.initials: E
authors.lastname: Oliveira
authors.forename: Thereza
authors.initials: T
authors.lastname: Trombini
authors.forename: Mateus
authors.initials: M
authors.lastname: Luchese
authors.forename: Saiuri
authors.initials: S
authors.lastname: Bisi
authors.forename: Rafael
authors.initials: R
authors.lastname: Linden
authors.forename: Daiane Bolzan
authors.initials: DB
authors.lastname: Berlese
authors.forename: Denise Bertin
authors.initials: DB
authors.lastname: Rojas
authors.forename: Rodrigo Binkowski
authors.initials: RB
authors.lastname: Andrade
authors.forename: Patricia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.forename: Larissa Machado
authors.initials: LM
authors.lastname: Lacerda
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Clovis Milton Duval
authors.initials: CM
authors.lastname: Wannmacher
authors.forename: Tatiana
authors.initials: T
authors.lastname: Emanuelli
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D004912:Erythrocytes; D005982:Glutathione Transferase / Q000378:metabolism; D015386:Hazardous Substances / Q000097:blood / Q000633:toxicity*; D006801:Humans; D007854:Lead / Q000097:blood / Q000633:toxicity*; D008297:Male; D008875:Middle Aged; D016273:Occupational Exposure / Q000032:analysis* / Q000706:statistics & numerical data; D000623:Porphobilinogen Synthase / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015386:Hazardous Substances; D007854:Lead; D005982:Glutathione Transferase; D011770:Pyruvate Kinase; D000623:Porphobilinogen Synthase