Prediction of pharmacokinetic properties and antioxidant action of octyl gallate and its effect on rat red blood cells and Candida spp. strains

Prediction of pharmacokinetic properties and antioxidant action of octyl gallate and its effect on rat red blood cells and Candida spp. strains

• Author
• Júlio César Pinheiro Lúcio de Oliveira
• Co-authors
• Larissa Alves da Silva , Luanna de Oliveira e Lima , Francisco Humberto Xavier Júnior , Felipe Queiroga Sarmento Guerra , Robson Cavalcante Veras
• Abstract

• INTRODUCTION: Candidiasis is a fungal infection caused by species of the genus Candida spp., often associated with systemic infections [1]. Due to the adverse effects of conventional treatments and the development of fungal resistance, there is growing interest in finding new antimycotic molecules. Octyl gallate is considered a safe substance, exhibiting low toxicity in humans [2]. However, its rapid elimination from the body and oily characteristics limit the routes of administration. To overcome these limitations, a microemulsion containing octyl gallate was developed. AIMS: Evaluate octyl gallate microemulsion on rat red blood cells, its antioxidant activity, prediction of in silico pharmacokinetic parameters and efficacy against Candida spp. strains. METHODS: The microemulsion was prepared using Cremophor EL, medium chain triglycerides, octyl gallate and deionized water. Sonication was used to form the octyl gallate microemulsion (MEGO). The antioxidant activity was evaluated using the DPPH radical scavenging method. To elucidate the hemolytic action of MEGO, washed rat red blood cells were used (CEUA/UFPB n°: 4129280422). The red blood cells were separated into polypropylene tubes and incubated with different concentrations of MEGO, vehicle or TritonX (positive control). The amount of hemoglobin was quantified by spectrophotometry. 100% hemolysis defined as the maximum absorbance generated by TritonX. The pharmacokinetic parameters were predicted using the pKCSM platform. Finally, the minimum inhibitory concentration (MIC) of MEGO was determined against strains of Candida albicans and Candida parapsilosis according to CLSI M37-A3 RESULTS AND DISCUSSION: MEGO was not shown to have a hemolytic effect on rat red blood cells, which corroborates its findings of low toxicity [1]. Furthermore, the antioxidant potency of octyl gallate in the microemulsion system was higher than that of ascorbic acid. In the in silico pharmacokinetic models studied, octyl gallate has been shown to have good intestinal absorption, but with a short half-life and low bioavailability due to the large amount of substance bound to proteins. In view of this, forms that increase absorption or allow it to be administered parenterally are essential (with a view to its systemic use). In terms of antifungal action, the formulation has increased its potency by dozens of times against species of the candida when looking at other published studies [1]. CONCLUSION: MEGO is a promising agent in the fight against infections caused by candida albicans and Candida parapsilosis. Furthermore, octyl gallate in this emulsion system could improve the observed pharmacokinetic parameters without potentiating its toxic effects observed in other published studies [1]. ACKNOWLEDGMENT: For Programa de Pós-Graduação em Produtos Naturais e Sintéticos Bioativos, UFPB, CNPq and CAPES

   

  Citations and References

  [1] SAIBABU, Venkata et al. Octyl gallate triggers dysfunctional mitochondria leading to ROS driven membrane damage and metabolic inflexibility along with attenuated virulence in Candida albicans. Medical mycology, v. 58, n. 3, p. 380-392, 2020.

  [2] EFSA PANEL ON FOOD ADDITIVES AND NUTRIENT SOURCES ADDED TO FOOD (ANS). Scientific Opinion on the re?evaluation of octyl gallate (E 311) as a food additive. EFSA Journal, v. 13, n. 10, p. 4248, 2015.

• Keywords
• Microemulsion, Pharmacokinetics, Fungicide, Red blood cells, DPPH.
• Modality
• Pôster
• Subject Area
• Biology, Pharmacology and Physiology