Genotoxicity and acute and subchronic toxicity studies of a bioactive polyoxometalate in Wistar rats

BMC Pharmacol Toxicol. 2017 Apr 5;18(1):26. doi: 10.1186/s40360-017-0133-x.

Abstract

Background: Cs2K4Na [SiW9Nb3O40] (POM93) is a novel broad-spectrum antiviral agent with high activity, high stability, and low toxicity in vitro. Most toxicity studies for POM93 have been performed in cultured cell lines rather than in animals. Like other POMs, there is a lack of evidence for in vivo toxicity limits, oral bioavailability, and therapeutic applications.

Methods: The toxic properties of POM93 were evaluated comprehensively in vivo, including the acute and subchronic oral toxicity studies and genotoxicity tests.

Results: The acute toxicity study showed no abnormal changes or mortality in rats treated with POM93 even at the single high dose of 5000 mg/kg body weight. In the subchronic toxicity study, regardless of the body weight, the organ weight, and the hematological parameters, similar results were observed between the control group and the experimental groups. POM93 produced mild changes in rare hematological parameters in the liver and kidneys, but did not induce the clinical symptoms of liver or kidneys injury in rats as confirmed by histopathological analysis. Moreover, neither mutagenicity nor clastogenicity was caused by POM93 treatment in vitro and in vivo.

Conclusions: The present study demonstrates that the oral administration of POM93 is presumed safe and poses a low risk of potential health risks.

Keywords: Acute oral toxicity; Genotoxicity; Polyoxometalate; Subchronic oral toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / toxicity*
  • Female
  • Kidney / drug effects
  • Liver / drug effects
  • Male
  • Mice, Inbred ICR
  • Micronucleus Tests
  • Mutagens / administration & dosage
  • Mutagens / toxicity*
  • Prospective Studies
  • Rats
  • Rats, Wistar
  • Salmonella typhimurium / drug effects
  • Toxicity Tests, Acute
  • Toxicity Tests, Subchronic
  • Tungsten Compounds / administration & dosage
  • Tungsten Compounds / toxicity*

Substances

  • Antiviral Agents
  • Mutagens
  • Tungsten Compounds
  • polyoxometalate I