Acute Exposure to Low Lead Levels and its Implications on the Activity and Expression of Cytosolic Thioredoxin Reductase in the Kidney

作者：Conterato Greicy M M; Quatrin Andreia; Somacal Sabrina; Ruviaro Amanda R; Vicentini Juliana; Augusti Paula R; Sobieski Rocheli; Figueiredo Cassieli; dos Santos Clarissa M M; Pereira Talita C B; Bogo Mauricio R; Flores Erico M M; Emanuelli Tatiana^*

来源：Basic and Clinical Pharmacology and Toxicology, 2014, 114(6): 476-484.

DOI：10.1111/bcpt.12183

Renal thioredoxin reductase-1 (TrxR-1) activity is stimulated at lead doses lower than that necessary to inhibit delta-aminolevulinate dehydratase activity (delta-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 delta-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 48hr after the exposure to 25mg/kg lead acetate (p<0.05), whereas its expression was increased 24 and 48hr 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 25mg/kg). Erythrocyte delta-ALA-D activity was inhibited 6hr after the exposure to 25mg/kg lead acetate (p<0.05) but recovered thereafter. Renal delta-ALA-D activity decreased 24 and 48hr after the exposure to 25mg/kg lead acetate. There were no changes in any parameters at lead acetate doses <25mg/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.

• 出版日期2014-6