title: Acute exposure to low lead levels and its implications on the activity and expression of cytosolic thioredoxin reductase in the kidney.
abstract: Renal thioredoxin reductase-1 (TrxR-1) activity is stimulated at lead doses lower than that necessary to inhibit δ-aminolevulinate dehydratase activity (δ-ALA-D), which is a classical early biomarker of lead effects. Thus, we hypothesized that the activity of TrxR-1 could be a more sensitive early indicator of lead effects than is δ-ALA-D. To evaluate this hypothesis, we assessed the blood and renal TrxR-1 activity and its gene expression along with biomarkers of oxidative damage, antioxidant enzyme activities and biomarkers of lead exposure in rats acutely exposed to lead. A histopathological analysis was performed to verify renal damage. The increase in renal TrxR-1 activity paralleled the increase in the blood and renal lead levels at 6, 24 and 48 hr after the exposure to 25 mg/kg lead acetate (p < 0.05), whereas its expression was increased 24 and 48 hr after exposure. These effects were not accompanied by oxidative or tissue damage in the kidneys. Blood TrxR-1 activity was not affected by lead exposure (up to 25 mg/kg). Erythrocyte δ-ALA-D activity was inhibited 6 hr after the exposure to 25 mg/kg lead acetate (p < 0.05) but recovered thereafter. Renal δ-ALA-D activity decreased 24 and 48 hr after the exposure to 25 mg/kg lead acetate. There were no changes in any parameters at lead acetate doses <25 mg/kg. Our results indicate that blood TrxR-1 activity is not a suitable indicator of lead effects. In contrast, the increase in renal TrxR-1 expression and activity is implicated in the early events of lead exposure, most likely as a protective cellular mechanism against lead toxicity.
authors.affiliation: Health Sciences Area, Community University of Chapeco Region, Chapecó, Brazil.
authors.forename: Greicy M M
authors.initials: GM
authors.lastname: Conterato
authors.forename: Andréia
authors.initials: A
authors.lastname: Quatrin
authors.forename: Sabrina
authors.initials: S
authors.lastname: Somacal
authors.forename: Amanda R
authors.initials: AR
authors.lastname: Ruviaro
authors.forename: Juliana
authors.initials: J
authors.lastname: Vicentini
authors.forename: Paula R
authors.initials: PR
authors.lastname: Augusti
authors.forename: Rocheli
authors.initials: R
authors.lastname: Sobieski
authors.forename: Cassieli
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Clarissa M M
authors.initials: CM
authors.lastname: dos Santos
authors.forename: Talita C B
authors.initials: TC
authors.lastname: Pereira
authors.forename: Maurício R
authors.initials: MR
authors.lastname: Bogo
authors.forename: Erico M M
authors.initials: EM
authors.lastname: Flores
authors.forename: Tatiana
authors.initials: T
authors.lastname: Emanuelli
mesh_terms: D000818:Animals; D003600:Cytosol / Q000201:enzymology*; D004912:Erythrocytes / Q000201:enzymology; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D000072019:Kelch-Like ECH-Associated Protein 1; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D007854:Lead / Q000493:pharmacokinetics / Q000633:toxicity*; D008297:Male; D000623:Porphobilinogen Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054481:Thioredoxin Reductase 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D007854:Lead; D054481:Thioredoxin Reductase 1; C516126:Txnrd1 protein, rat; D000623:Porphobilinogen Synthase