Lead Does Not Affect Transcription of Intestinal Zinc-Binding Proteins in Growing Rats:

Abstract

Environmental lead exposure remains a serious concern for the growth and development of children. Micronutrient status may affect the absorption and tissue accumulation of lead, but the mechanisms of gastrointestinal uptake and transport remain unknown. Thus, our objective was to investigate the effects of lead on the mRNA levels of intestinal zinc transporter 4 (ZIP4), metallothionein (MT), cysteine-rich intestinal protein (CRIP), and divalent metal transporter 1 (DMT1) in growing rats fed marginal, adequate, and supplemental zinc diets. Weanling Sprague Dawley rats were assigned to marginal zinc (MZ; 8 mg Zn/kg diet), zinc-adequate control (CT; 30 mg Zn/kg), zinc-adequate diet-restricted (DR; 30 mg Zn/kg), or supplemental zinc (SZ; 300 mg Zn/kg) groups, with and without lead acetate-containing drinking water (200 mg Pb/l) for 3 weeks. Duodenum was analyzed for ZIP4, MT, CRIP, and DMT1 mRNA levels by real-time reverse transcription-polymerase chain reaction and MT immunolocalization. Tissues were analyzed for zinc, lead, and iron by inductively coupled plasma spectrometry. MZ rats had higher duodenal ZIP4 mRNA levels, lower MT mRNA levels, lower MT immunostaining intensity, and lower zinc concentrations than DR, CT, and SZ. Duodenal DMT1 mRNA levels were lower in DR and SZ compared with MZ. Tissue lead concentrations responded to dietary zinc with SZ < CT < DR <or= MZ. The greater accumulation of hepatic lead in MZ rats was associated with zinc deficiency as well as diet restriction. Lead treatment resulted in higher hepatic iron concentrations but had no effect on duodenal ZIP4, MT, CRIP, or DMT1 mRNA levels. Thus, tissue lead accumulation was not directly mediated by the transcriptional induction of zinc and iron binding or transport proteins. The mechanisms of lead absorption during nutritional deficiency and supplementation require further investigation.