Sex-specific effects of gestational and lactational coexposure to lead and cadmium on hepatic phase I and phase II xenobiotic/steroid-metabolizing enzymes and antioxidant status

Prakash Pillai, Ritesh Patel, Chirayukumar D Pandya, Sarita Gupta

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Liver has evolved complex enzymatic mechanisms to detoxify a wide array of xenobiotic substances, ranging from dietary components to environmental toxins to pharmaceuticals. Activities of many steroid-metabolizing enzymes in adult rat liver microsomes are sexually differentiated. Toxic effects of lead and cadmium on hepatic tissue have been well established in our earlier studies. We thus monitored the effects of gestational and lactational coexposure to lead and cadmium on hepatic phase I and phase II xenobiotic- and steroid-metabolizing enzyme activities in both male and female F1 generation postnatal day (PND) 56 rats. Adult pregnant female rats were treated subcutaneously [0.05 mg/(kg body wt. day)] with sodium acetate (control group), lead acetate, and cadmium acetate separately and in combination throughout the gestational and lactational period. Hepatic phase I xenobiotic-metabolizing enzymes (NADPH- and NADH-cytochrome c reductase) activities significantly decreased significantly in all the metal-treated groups in both PND 56 male and female rats as compared with the control group. Hepatic phase II enzymes (uridine diphosphate- glucuronosyl transferase, γ-glutamyl transpeptidase, glutathione- Stransferase, 17-β-hydroxysteroid oxidoreductase)were also highly susceptible to all the metal-treated groups. The observed alterations in the oxidative stress and biochemical parameters in the liver of F1 generation male and female rats resulted from an independent effect of lead and/or cadmium and also from their interaction. Results suggest that early developmental exposure to lead and cadmium both alone and in combination can suppress the hepatic xenobioticmetabolizing enzyme activities in the liver of F1 generation male and female rats in a sex-dependent manner.

Original languageEnglish (US)
Pages (from-to)419-431
Number of pages13
JournalJournal of Biochemical and Molecular Toxicology
Volume23
Issue number6
DOIs
StatePublished - Nov 1 2009

Keywords

  • Cadmium
  • Gestational and lactational exposure
  • Hepatic steroid-metabolizing enzymes
  • Lead

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

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