Chronic Cadmium Exposure Lead to Inhibition of Serum and Hepatic Alkaline Phosphatase Activity in Wistar Rats

J Biochem Mol Toxicol. 2015 Dec;29(12):587-94. doi: 10.1002/jbt.21732. Epub 2015 Jul 27.

Abstract

Alkaline phosphatase (ALP) activity in the serum and liver from rats administered with cadmium (Cd) in drinking water was studied. After metal administration, Cd showed a time-dependent accumulation in the liver, meanwhile metallothionein had a maximum increase at 1 month, remaining in this level until the end of the study. On the other hand, serum and liver ALP activity was decreased after 3 months exposure. To determine if Cd produced an inhibition on enzyme, apo-ALP prepared from both nonexposed and exposed rats was reactivated with Zn, showing 60% more activity as compared with the enzyme isolated from nonexposed rats. In vitro assays showed that Cd-ALP was partially reactivated with Zn; however, in the presence of cadmium, Zn-ALP was completely inhibited. Kinetic studies indicate a noncompetitive inhibition by Cd; these results suggest that Cd can substitute Zn, and/or Cd can interact with nucleophilic ligands essential for the enzymatic activity.

Keywords: Alkaline Phosphatase; Cadmium; Enzymatic Inhibition.

MeSH terms

  • Alkaline Phosphatase / antagonists & inhibitors
  • Alkaline Phosphatase / blood
  • Alkaline Phosphatase / metabolism*
  • Animals
  • Binding, Competitive
  • Cadmium / metabolism
  • Cadmium / toxicity*
  • Kinetics
  • Liver / drug effects*
  • Liver / enzymology
  • Male
  • Rats
  • Rats, Wistar
  • Zinc / metabolism

Substances

  • Cadmium
  • Alkaline Phosphatase
  • Zinc