RESUMO
Emerging contaminants, such as the herbicides trifluralin and tebuthiuron, comprise a class of compounds for which toxicological data are lacking, especially data regarding their harmful effects and biomarkers of exposure. Their potential damage to the environment and non-target organisms makes understanding their toxic mechanisms an urgent matter. Mitochondria, which exert an energy production function, play a vital role in maintaining many cellular activities and therefore are reliable predictors of substance toxicity. This study evaluates whether the herbicides trifluralin and tebuthiuron (at concentrations ranging from 1 to 100 µM) affect isolated rat liver mitochondria. The herbicides were analyzed according to their ability to interact with the mitochondrial membrane and induce swelling, lipoperoxidation, ROS formation, and NAD(P)H oxidation; dissipate the membrane potential; dysregulate calcium homeostasis; and alter ATP and GSH/GSSG levels. Tebuthiuron does not disrupt the mitochondrial biochemistry at any of the tested concentrations. In contrast, trifluralin can disturb the mitochondrial respiration, especially at the highest concentration, but it cannot induce oxidative stress. These results suggest that the aforementioned effects can occur as toxic mechanisms of trifluralin in non-target organisms, as well.
Assuntos
Herbicidas , Trifluralina , Animais , Compostos de Metilureia , Mitocôndrias , Mitocôndrias Hepáticas , RatosRESUMO
Humans and animals can be exposed to different chemical forms of mercury (Hg) in the environment. For example, methylmercury (MeHg)-contaminated fish is part of the basic diet of the riparian population in the Brazilian Amazon Basin, which leads to high total blood and plasma Hg levels in people living therein. Hg induces toxic effects mainly through oxidative stress. Different compounds have been used to prevent the damage caused by MeHg-induced reactive oxygen species (ROS). This study aims to investigate the in vivo effects of sub-chronic exposure to low MeHg levels on the mitochondrial oxidative status and to evaluate the niacin protective effect against MeHg-induced oxidative stress. For this purpose, Male Wistar rats were divided into four groups: control group, treated with drinking water on a daily basis; group exposed to MeHg at a dose of 100 µg/kg/day; group that received niacin at a dose of 50 mg/kg/day in drinking water, with drinking water being administered by gavage; group that received niacin at a dose of 50 mg/kg/day in drinking water as well as MeHg at a dose of 100 µg/kg/day. After 12 weeks, the rats, which weighed 500-550 g, were sacrificed, and their liver mitochondria were isolated by standard differential centrifugation. Sub-chronic exposure to MeHg (100 µg/kg/day for 12 weeks) led to mitochondrial swelling (p < 0.05) and induced ROS overproduction as determined by increased DFCH oxidation (p < 0.05), increased gluthatione oxidation (p < 0.05), and reduced protein thiol content (p < 0.05). In contrast, niacin supplementation inhibited oxidative stress, which counteracted and minimized the toxic MeHg effects on mitochondria.
Assuntos
Compostos de Metilmercúrio/toxicidade , Mitocôndrias Hepáticas/efeitos dos fármacos , Niacina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Masculino , Compostos de Metilmercúrio/administração & dosagem , Mitocôndrias Hepáticas/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Technological, agricultural, and medical advances have improved the lifestyle of humankind. However, these advances have caused new problems that affect the environment and future generations. Emerging contaminants display properties such as low degradation potential and environmental persistence. In addition, most contaminants are lipophilic, which culminates in high bioaccumulation. The disposal of pharmaceuticals and personal care products into the environment underlies microbial and bacterial resistance. Plasticizers change several characteristics of industrialized materials, such as flexibility, but they are potentially carcinogenic and disrupt the endocrine system. Pesticides prevent the propagation of numerous kinds of pests; nevertheless, they exert neurotoxic and mutagenic effects, and they impact the environment negatively. Addition of flame retardants to a number of materials prevents flame propagation; however, after their release into the environment, these chemicals may bioaccumulate in organisms and disrupt the endocrine system, too. Surfactants can change the surface and interfacial properties of liquids, but their presence in the environment can interfere with countless enzymes and can even impair the endocrine system of various organisms and induce the feminization of species. Hence, gaining knowledge about emerging contaminants is increasingly important to minimize future damage and enable proper monitoring of each class of compounds in the environment which will help to improve legislation on this matter.
Assuntos
Meio Ambiente , Poluentes Ambientais/toxicidade , Saúde , Animais , Ecotoxicologia , Humanos , RiscoRESUMO
Monensin A is a commercially important natural product isolated from Streptomyces cinnamonensins that is primarily employed to treat coccidiosis. Monensin A selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties. In this study, we evaluated the Jacobsen catalyst as a cytochrome P450 biomimetic model to investigate the oxidation of monensin A. Mass spectrometry analysis of the products from these model systems revealed the formation of two products: 3-O-demethyl monensin A and 12-hydroxy monensin A, which are the same ones found in in vivo models. Monensin A and products obtained in biomimetic model were tested in a mitochondrial toxicity model assessment and an antimicrobial bioassay against Staphylococcus aureus, S. aureus methicillin-resistant, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli. Our results demonstrated the toxicological effects of monensin A in isolated rat liver mitochondria but not its products, showing that the metabolism of monensin A is a detoxification metabolism. In addition, the antimicrobial bioassay showed that monensin A and its products possessed activity against Gram-positive microorganisms but not for Gram-negative microorganisms. The results revealed the potential of application of this biomimetic chemical model in the synthesis of drug metabolites, providing metabolites for biological tests and other purposes.