RESUMO
Imazamox (IMX), a chiral herbicide used in cereals and oilseed crops to control weeds, is commonly sold as a racemic mixture. Its enantiomers, being chiral compounds, may exhibit unique properties when exposed to chiral environments. While IMX enantiomers have been reported to degrade differently in soil and be toxic to some species, their effects on human systems remain poorly understood. This study utilized Caco-2 (human colon adenocarcinoma cell line) cells to assess the in vitro permeability of a racemic mixture of IMX and its isolated enantiomers. Additionally, the study aimed to evaluate whether the metabolite imazamox-O-desmethyl (IMX-D) forms during the permeability process. An enantioselective chromatographic method was developed, fully validated, and the apparent permeability values were obtained. The apparent permeability of rac-IMX, (+)-IMX, and (-)-IMX was determined to be 4.15 × 10-5, 5.78 × 10-5, and 7.33 × 10-5 cm s-1, respectively. These findings suggest that IMX exhibits high intestinal permeability, with an enantioselective absorption for (-)-IMX as compared to (+)-IMX. Finally, the permeability study in Caco-2 cells revealed that the metabolite IMX-D was not generated.
Assuntos
Permeabilidade , Humanos , Células CACO-2 , Estereoisomerismo , Imidazóis/química , Imidazóis/metabolismo , Reprodutibilidade dos Testes , Limite de Detecção , Modelos Lineares , Cromatografia Líquida de Alta Pressão/métodos , Praguicidas/química , Praguicidas/metabolismoRESUMO
Human exposure to contaminants of emerging concern, like pesticides, has increased in the past decades. Diclofop-methyl (DFM) is a chiral herbicide that is employed as a racemic mixture (rac-DFM) in soybean and other crops against wild oats. Studies have shown that DFM has enantioselective action (higher for R-DFM), degradation (faster for S-DFM), and metabolism, producing diclofop (DF) which is also a pesticide. Although toxic effects have been reported for DFM, information regarding how DFM affects humans is lacking, especially when its chirality is concerned. In this study, the in vitro metabolism of rac-DFM and its isolated enantiomers was assessed by using a human model based on human liver microsomes. The kinetic model and parameters were obtained, and the hepatic clearance (CLH) and hepatic extraction ratio (EH) were estimated. Enzyme phenotyping was carried out by employing carboxylesterase isoforms (CES 1 and CES 2). DFM was metabolized through positive homotropic cooperativity with slight preference for (-)-DFM metabolism to (-)-DF. CLH and EH were above 19.60 mL min-1 kg-1 and 98 % for all the monitored reactions, respectively, and CES 1 was the main enzyme underlying the metabolism. These findings point out that liver contributes to DFM metabolism, which is fast, resulting in nearly complete conversion to DF after exposition to DFM.
Assuntos
Herbicidas , Praguicidas , Humanos , Herbicidas/toxicidade , Estereoisomerismo , Toxicocinética , Praguicidas/toxicidadeRESUMO
Although iron oxide occurs naturally in the environment, iron oxide nanoparticles have distinct mobility, reactivity, and toxicity, which can harm the human health and nature. This scenario has motivated the investigation of the toxic effects of iron oxide nanoparticles (akaganeite predominance + hematite) on the aquatic plant Lemna minor. First, nanoparticles were synthesized and characterized; then, different iron oxide NP concentrations were added to Lemna minor culture. After 7 days, all the Lemna minor leaves died, irrespective of the added NP concentration. The iron oxide NP impact on the plant was evaluated based on malondialdehyde (MDA) production from thiobarbituric acid reactive substances (TBARS), which was dose-dependent; i.e., lipid peroxidation in the plant increased with rising iron oxide NP concentration. The chlorophyll content decreased at high iron oxide NP concentrations, which disrupted the light absorption mechanism. Fe accumulation in Lemna minor roots also occurred, which can harm nutrient uptake. Therefore, the iron oxide NP toxic impact on plants and related ecosystems requires further studies in order to prevent environmental damage.