Search

Diazinon is an organophosphorus pesticide, which may have potential toxic effects on the liver and immune system; however, the underlying mechanisms remain mostly unidentified. This work is aimed at evaluating the oxidative stress and cell cycle alterations elicited by low-dose diazinon in a rat liver cell line (BRL-3A) and spleen mononuclear cells (SMC) from Wistar rats. Diazinon (10–50 μM) caused early reactive oxygen species (ROS) generation (from 4 h) as well as increased O2•- level (from 0.5 h), which led to subsequent lipid peroxidation at 24 h, in BRL-3A cells. In SMC, diazinon (20 μM) produced similar increases in ROS levels, at 4 and 24 h, with the highest O2•- level being found at 4 h. Low-dose diazinon induced G1-phase arrest and cell death in hepatic cells and SMC. Therefore, diazinon could affect the liver and the immunological system through the premature oxidative stress induction. Abbreviations: O2•-: superoxide anion radical; ROS: reactive oxygen species; SMC: spleen mononuclear cells; TBARS: thiobarbituric acid reactive substances [ABSTRACT FROM AUTHOR]

Human oral exposure to aflatoxin B1 (AFB1) and fumonisin B1 (FB1) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB1-FB1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB1-FB1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB1 metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors. Flow cytometry of stained BRL-3A hepatocytes was used to study the cell cycle (propidium iodide), ROS intracellular production (DCFH-DA, HE, DAF-2 DA), and phospholipase A activity (staining with bis-BODIPY FL C11-PC). The CYP1A activity was assessed by the 7-ethoxyresorufin-O-deethylase (EROD) assay. Despite a 48-h exposure to FB1 (30 μM) not being genotoxic, the AFB1 (20 μM)-induced micronucleus frequency was overcome by the AFB1-FB1 mixture (MIX), presumably showing toxin interaction. The mycotoxins blocked G1/S-phase, but only MIX caused cell death. Overall, the oxidative stress led these alterations as the pretreatment with N-acetyl-l-cysteine reduced such toxic effects. While AFB1 had a major input to the MIX pro-oxidant activity, with CYP and ArAc metabolism being ROS contributors, these pathways were not involved in the FB1-elicited weak oxidative stress. The MIX-induced micronucleus frequency in N-acetyl- l-cysteine pretreated cells was greater than that caused by AFB1 without antioxidants, suggesting enhanced AFB1 direct genotoxicity probably owing to the higher CYP activity and ArAc metabolism found in MIX. The metabolic pathways modulation by AFB1-FB1 mixtures could raise its hepatocarcinogenic properties. [ABSTRACT FROM AUTHOR]

Considering the impact of Aspergillus species on crops, it appears to be highly desirable to apply strategies to prevent their growth, as well as to eliminate or reduce their presence in food products. For this reason, the aims of this investigation were to evaluate the effects of ten natural phenolic compounds on the Aspergillus parasiticus growth and to determine which physicochemical properties are involved in the antifungal activity. According to the results of minimum inhibitory concentration (MIC) values of the individual compounds, isoeugenol, carvacrol, and thymol were the most active phenolic components (1.26 mM, 1.47 mM, and 1.50 mM, resp.), followed by eugenol (2.23 mM). On the other hand, creosol, p-cresol, o-cresol, m-cresol, vanillin, and phenol had no effects on fungal development. Logarithm of the octanol/water partition coefficient (log P), refractivity index (RI), and molar volume (MV) were demonstrated to be the descriptors that best explained the antifungal activity correlated to lipophilicity, reactivity of the components, and steric aspect. These findings make an important contribution to the search for new compounds with antifungal activity. [ABSTRACT FROM AUTHOR]

Abstract: Fumonisin B1 (FB1) is a Fusarium mycotoxin that has received considerable attention from food regulatory agencies, since it shows immunotoxic, neurotoxic, hepatotoxic, nephrotoxic and carcinogenic properties in animals. Although several publications have reported that some natural phenolic compounds can cause a reduction in mycotoxin production, little is known about the molecular properties related to their antitoxigenic activities. The objective of this work was to evaluate which of these molecular properties are important in antifumonisin activity, with this being the first structure–activity relationship study concerning the antimyctoxigenic activity of natural phenolic compounds. The results of the experimental determination of the FB1 inhibition capacity for ten natural phenolic compounds revealed thymol, carvacrol, and isoeugenol followed by eugenol to be the most active antifumonisin compounds. Lipophilicity, molar refractivity and saturated area were demonstrated to be the molecular properties or descriptors which best explained the antifumonisin activity of these phenolic compounds. A mathematical expression, obtained by QSAR analysis, was able to predict the antifumonisin activity of other structurally related molecules. These findings could provide an important contribution in the search for new compounds with antifumonisin activity. [Copyright &y& Elsevier]

Abstract: Menthol is a naturally occurring cyclic terpene alcohol of plant origin from the Lamiaceae family. It has three chiral centres, implying eight possible different stereoisomers, which in turn define four pairs of enantiomers. This is the first work that reports on the stereoselective antifungal and antitoxigenic activities of the menthol stereoisomers on Fusarium verticillioides, with the (−)-menthol and (+)-menthol enantiomers found to be the most active inhibitors of fungal growth and sporulation. The results obtained suggest the importance of the presence of these substituents in the equatorial positions of menthol stereoisomers in the antifungal activity. The stereoisomer (−)-menthol, followed by (+)-menthol, were the most active compounds in the inhibition of fumonisin B1 (FB1) biosynthesis. The different antitoxigenic activities of (−)-menthol and (+)-menthol revealed that the molecular requirements to affect the FB1 production were dependent not only on the presence of the substituents in the equatorial positions, but also on their spatial arrangements. [Copyright &y& Elsevier]

Human oral exposure to aflatoxin B 1 (AFB 1 ) and fumonisin B 1 (FB 1 ) is associated with increased hepatocellular carcinoma. Although evidence suggested interactive AFB 1 -FB 1 hepatotoxicity, the underlying mechanisms remain mostly unidentified. This work was aimed at evaluating the possible AFB 1 -FB 1 interplay to induce genetic and cell cycle toxicities in BRL-3A rat hepatocytes, reactive oxygen species (ROS) involvement, and the AFB 1 metabolizing pathways cytochrome P450 (CYP) and arachidonic acid (ArAc) metabolism as ROS contributors. Flow cytometry of stained BRL-3A hepatocytes was used to study the cell cycle (propidium iodide), ROS intracellular production (DCFH-DA, HE, DAF-2 DA), and phospholipase A activity (staining with bis-BODIPY FL C11-PC). The CYP1A activity was assessed by the 7-ethoxyresorufin-O-deethylase (EROD) assay. Despite a 48-h exposure to FB 1 (30 μM) not being genotoxic, the AFB 1 (20 μM)-induced micronucleus frequency was overcome by the AFB 1 -FB 1 mixture (MIX), presumably showing toxin interaction. The mycotoxins blocked G1/S-phase, but only MIX caused cell death. Overall, the oxidative stress led these alterations as the pretreatment with N-acetyl-l-cysteine reduced such toxic effects. While AFB 1 had a major input to the MIX pro-oxidant activity, with CYP and ArAc metabolism being ROS contributors, these pathways were not involved in the FB 1 -elicited weak oxidative stress. The MIX-induced micronucleus frequency in N-acetyl-l-cysteine pretreated cells was greater than that caused by AFB 1 without antioxidants, suggesting enhanced AFB 1 direct genotoxicity probably owing to the higher CYP activity and ArAc metabolism found in MIX. The metabolic pathways modulation by AFB 1 -FB 1 mixtures could raise its hepatocarcinogenic properties., (© 2017 Wiley Periodicals, Inc.)