The acute systemic toxicity of thallium in rats produces oxidative stress: attenuation by metallothionein and Prussian blue

Biometals. 2021 Dec;34(6):1295-1311. doi: 10.1007/s10534-021-00343-8. Epub 2021 Sep 16.

Abstract

Thallium (TI) is one of the most toxic heavy metals. Human exposure to Tl occurs through contaminated drinking water and from there to food, a threat to health. Recently, environmental contamination by Tl has been reported in several countries, urging the need for studies to determine the impact of endogenous and exogenous mechanisms preventing thallium toxicity. The cytoprotective effect of metallothionein (MT), a protein with high capacity to chelate metals, at two doses (100 and 600 µg/rat), was tested. Prussian blue (PB) (50 mg/kg) was administered alone or in combination with MT. A dose of Tl (16mg/kg) was injected i.p. to Wistar rats. Antidotes were administered twice daily, starting 24h after Tl injection, for 4 days. Tl concentrations diminished in most organs (p < 0.05) by effect of PB, alone or in combination with MT, whereas MT alone decreased Tl concentrations in testis, spleen, lung and liver. Likewise, brain thallium also diminished (p < 0.05) by effect of PB and MT alone or in combination in most of the regions analyzed (p < 0.05). The greatest diminution of Tl was achieved when the antidotes were combined. Plasma markers of renal damage increased after Tl administration, while PB and MT, either alone or in combination, prevented the raise of those markers. Only MT increased the levels of reduced glutathione (GSH) in the kidney. Finally, increased Nrf2 was observed in liver and kidney, after treatment with MT alone or in combination with PB. Results showed that MT alone or in combination with PB is cytoprotective after thallium exposure.

Keywords: Metallothionein; Nrf2; Oxidative stress; Prussian blue; Reduced glutathione; Systemic toxicity; Thallium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ferrocyanides
  • Male
  • Metallothionein* / metabolism
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Thallium* / metabolism
  • Thallium* / toxicity

Substances

  • Ferrocyanides
  • Metallothionein
  • Thallium
  • ferric ferrocyanide