Abstract
This study aims to determine the toxicity, genotoxicity and antioxidative defense capacities of isopentanyl ferulate (IF), an ester derivative of ferulic acid (FA). Therefore, albino mice (25-30 g) were treated with 1000 to 3000 mg/kg orally (p.o.) and intraperitoneally (i.p.) to determine median lethal dose (LD50), biochemical and hematological parameters, motor coordination and genotoxic activity by comet assay. In addition, oxidative defense was assessed in Saccharomyces cerevisiae with one proficient (Sod wt), three single mutant (Sod1∆, Sod2∆ and Cat1∆) and two double mutants (Sod1∆Sod2∆ and Sod1∆Cat1∆), where IF in a dose range of 0.10 to 0.30 g/ml was used. Results suggest that IF produced LD50 by 1494.54 mg/kg. There was a bit change in biochemical and hematological parameters compared to the control group. Although, IF did not affect locomotor activity in test animals (both sexes) assessed by open field test (OFT) but it produced genotoxic activity at doses 1500 mg/kg (i.p.) and 3000 mg/kg (p.o.), whosever is higher than the LD50. Antioxidative defense to the S. cerevisiae cells and damage repair capability in both comet and S. cerevisiae assays indicate IF for a promising pharmacological moiety. In conclusion, IF produced low toxicity, genotoxicity at high dose with antioxidative defense and damage repair capability. Key words: Antioxidant, genotoxicity, isopentanyl ferulate, toxicity.
Highlights
This study aims to determine the toxicity, genotoxicity and antioxidative defense capacities of isopentanyl ferulate (IF), an ester derivative of ferulic acid (FA)
The proficient (Sod wt) and deficient (Sod1∆, Sod2∆, Cat1∆, Sod1∆Sod2∆ and Sod1∆Cat1∆) S. cerevisiae strains were kindly provided by the research group in Genetic Toxicology, Federal University of Rio Grande do Sul (UFRGS), Brazil
Effects of IF on biochemical and hematological parameters in Swiss mice Biochemical data presented in Table 4 indicate that most of the parameters tested were not significantly altered by VEC (10 ml/kg)
Summary
25% of allopathic drugs are derived from herbal compounds currently, and many others synthetic analogues are developed in prototype compounds isolated from plant species (Bhat et al, 2013). Plants have a variety of compounds which have no obvious functions in growth and development, called secondary metabolites. Study of these metabolites led to a current focus on discovery of new drugs (Marques et al, 2013). Both the discovery of natural or synthetic compounds with pharmacological properties and their action mechanism have major challenges for drug discovery and development. Toxicity information is required for both bioactive compounds from natural sources and their derivatives (Ping et al, 2013)
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