A 28-day Sub-acute Genotoxic and Behavioural Assessment of Garcinielliptone FC

Basic Clin Pharmacol Toxicol. 2018 Aug;123(2):207-212. doi: 10.1111/bcpt.13010. Epub 2018 May 23.

Abstract

Garcinielliptone FC (GFC) is a polyisoprenylated benzophenone isolated from Platonia insignis Mart (Clusiaceae) with promising anticonvulsant properties. However, its safe use and other effects on the central nervous system require assessment. This study assessed the toxicological effects of GFC using the comet assay and the micronucleus test in mice treated for 28 days. A behavioural model was employed to detect possible injuries on the central nervous system. Mice treated with GFC (2, 10 and 20 mg/kg; i.p.) daily for 28 days were submitted to rotarod test, open-field test and tail suspension test (TST). After the behaviour tasks, biological samples were assessed to evaluate genotoxic and mutagenic effects using the comet assay and the micronucleus test. Garcinielliptone FC did not impair the performance of the animals in the rotarod and open-field tests, with no antidepressant-like effect in TST. No genotoxic effects in blood and cerebral cortex were observable in the comet assay; however, there was a significant increase in index and frequency of damage in liver after treatment with GFC 20 mg/kg. Garcinielliptone FC did not increase micronucleus frequency in bone marrow. At the tested doses, GFC was not toxic to the CNS and did not induce genotoxic damage to blood or bone narrow cells. DNA damage to liver tissue was caused only by the highest dose, although no mutagenic potential was observed.

MeSH terms

  • Animals
  • Anticonvulsants / isolation & purification
  • Anticonvulsants / toxicity*
  • Behavior, Animal / drug effects*
  • Central Nervous System / drug effects*
  • Clusiaceae / chemistry
  • Comet Assay
  • DNA Damage / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Injections, Intraperitoneal
  • Liver / drug effects
  • Male
  • Mice
  • Micronucleus Tests
  • Models, Animal
  • Rotarod Performance Test
  • Toxicity Tests, Subacute
  • Treatment Outcome
  • Triterpenes / isolation & purification
  • Triterpenes / toxicity*

Substances

  • Anticonvulsants
  • Triterpenes
  • garcinielliptone FC