Cytotoxicity, mutagenicity, and antimutagenicity of the gentisic acid on HTC cells

Drug Chem Toxicol. 2018 Apr;41(2):155-161. doi: 10.1080/01480545.2017.1322606. Epub 2017 May 16.

Abstract

Gentisic acid (GA) exhibits antioxidant, anti-inflammatory, and antibiotic activities. This substance can be found in citrus fruits, grapes, olive oil, and peas. Considering that there are few studies in the literature on the toxicity of GA, the present work aimed to investigate its cytotoxic, mutagenic, and antimutagenic activities on HTC cells. GA was diluted in culture medium at the final concentration of 0.08, 0.16, 0.8, 1.6, and 8 μg/mL. The cytotoxicity was determined by the MTT assay and Trypan Blue exclusion method, with methyl methanesulfonate and doxorubicin as positive controls, respectively. The cytokinesis-block micronucleus assay determined the mutagenic/antimutagenic activity with benzo[a]pyrene as positive control. Negative control received culture medium only. GA (0.08-8 μg/mL) was not cytotoxic to HTC cells by the MTT assay nor the Trypan Blue exclusion method as no statistical difference was observed when compared to the control. Concentration of 0.08 and 0.8 μg/mL showed no mutagenic or clastogenic effects, as no significant micronuclei inductions were observed, different from 8 μg/mL, that was mutagenic. Furthermore, none of the concentrations presented an antiproliferative activity. The antimutagenic activity of GA (0.08 μg/mL) was observed at the simultaneous treatment, as it reduced the frequency of micronuclei by 76% (24 h) and 79% (48 h). Although pre- and post-treatments were not statistically different from the mutagen, they reduced the induced-damage by 11% and 21%, respectively. The present study indicated the absence of cytotoxicity and antiproliferative activities of GA, in addition to their antimutagenic/protective effects that may contribute to human health.

Keywords: HTC cells; MTT assay; Phenolic compound; clastogenicity; gentisic acid; micronuclei; protective activity.

MeSH terms

  • Animals
  • Antimutagenic Agents / pharmacology*
  • Antimutagenic Agents / toxicity
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Gentisates / pharmacology*
  • Gentisates / toxicity
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Hepatocytes / pathology
  • Micronuclei, Chromosome-Defective / chemically induced
  • Micronucleus Tests
  • Mutagens / pharmacology*
  • Mutagens / toxicity
  • Rats
  • Risk Assessment
  • Time Factors

Substances

  • Antimutagenic Agents
  • Gentisates
  • Mutagens
  • 2,5-dihydroxybenzoic acid