Toxicological analysis and efficacy of 2-phenylchromone on mycobacteria viability and inflammatory response induced by Mycobacterium bovis

Abstract

Background: Studies have reported that compounds similar to flavone present antimicrobial and anti-inflammatory properties; however these effects are poorly described in the context of mycobacterium infection. Purpose: This study investigated the efficacy of 2-phenylchromone (Flavone) on mycobacteria viability and inflammatory response induced by Mycobacterium bovis, as well as its toxicological potential in in vitro and in vivo models. Methods: In vitro antimycobacterial activity was performed using the resazurin microtiter assay method. In order to investigate the anti-inflammatory action, C57Bl/6 mice were pretreated orally with 2-phenylchromone (1–100 mg/kg) 1 h before the pleurisy induction. The leukocyte migration and cytokine production were evaluated. Acute oral toxicity test, genotoxicity evaluations and splenic phagocytosis assay were also evaluated. Results: The minimum inhibitory concentration of 2-phenylchromone in the presence of the Mycobacterium tuberculosis strain was 28.90 µg/mL. In the BCG-induced pleurisy model, the oral treatment with 2-phenylchromone (1, 10, or 100 mg/kg) caused a significant reduction in the tumor necrosis factor (TNF) levels in the pleural exudate, as well as in the total and differential leukocyte counts. The oral treatment with 2-phenylchromone also did not present acute toxicity or genotoxicity in comet assay and micronucleus tests. However, 2-phenylchromone induced an increase of 1.48-times in splenic phagocytosis in the animals. Conclusion: Our results showed that 2-phenylchromone did not induced toxicity signs and is effective against Mycobacterium viability and reduced the inflammatory response elicited by mycobacteria.

Keywords

• Mycobacterium tuberculosis
• Minimum inhibitory concentration
• Acute toxicity
• Comet assay
• Micronucleus test
• Pleurisy