Zinc-induced arsenite tolerance in mice

Area of Science:

• Toxicology
• Biochemistry
• Environmental Health

Background:

• The mechanism of arsenic toxicity tolerance remains unclear.
• Metallothionein (MT), a metal-binding protein, is known to reduce toxicity of certain metals.
• Arsenic has been shown to induce MT, suggesting a potential role in arsenic tolerance.

Purpose of the Study:

• To investigate the role of metallothionein (MT) in arsenic toxicity.
• To determine the mechanism by which zinc (Zn) pretreatment protects against arsenite lethality.
• To examine the effect of Zn pretreatment on arsenic distribution and elimination.

Main Methods:

• Mice were pretreated with zinc (Zn) to induce hepatic metallothionein (MT).
• Lethal effects of arsenite were assessed in Zn-pretreated and control mice.
• Subcellular distribution of arsenic-73 and its binding to MT were analyzed.
• Arsenic-73 content in various tissues was measured to assess elimination.

Main Results:

• Zn pretreatment significantly increased hepatic MT levels and protected against arsenite lethality.
• No direct correlation was observed between MT induction and protection against arsenic toxicity across various inducers.
• Zn pretreatment did not alter arsenic distribution in liver, kidney, or small intestine cytosol or organelles.
• Significantly lower arsenic-73 levels were found in blood and tissues of Zn-pretreated mice, indicating enhanced arsenic elimination.

Conclusions:

• Zinc pretreatment confers protection against arsenite toxicity in mice.
• The protective mechanism is not mediated by the induction of metallothionein (MT).
• Enhanced arsenic elimination appears to be the primary mechanism of zinc-induced tolerance to arsenic toxicity.