RESUMO
To achieve a waste-free clean production, the present study aimed to valorize an underused agroindustrial byproduct (rice bran) by mealworms bioconversion and produce bio-oil from pyrolysis of insect excreta (frass) as bioinsecticide. To reach the first goal, the suitability of rice bran (RB) versus standard diet, wheat bran (WB), was examined by determining feed conversion, growth performance, and nutritional profile of T. molitor larvae. RB diet was an appropriate feed substrate for breeding mealworms, as evidenced by their high survival rates, optimal feed conversion parameters, and its capability to support the growth and life cycle of this insect. Besides, RB did not affect soluble larval protein content but modified crude fat content and fatty acid profile. In order to address the second aim, egested frass from RB and WB were subjected to pyrolysis to obtain bio-oils. The main compound was acetic acid (≈37%) followed by 1,6-anhydro-ß-d-glucopyranose (from 16 to 25%), as measured by GC-MS analysis. Nitrogen-containing chemicals accounted for ≈10%. Frass bio-oils could represent a novel source of bioinsecticides due to their bioeffectiveness in insect pests of economic importance (Plodia interpunctella and Tribolium castaneum) and medical interest (Culex pipiens pipiens). For P. interpunctella adults, frass bio-oils produced insecticidal activity by fumigant and contact exposure whereas for T. castaneum adults, just fumigant. By a miniaturized model that simulates semireal storage conditions, it was seen that, on T. castaneum, frass RB bio-oil generated higher repellent effect than frass WB. Finally, bio-oils proved to have larvicidal activity against Cx. p. pipiens.
Assuntos
Tenebrio , Animais , Pirólise , Óleos de Plantas , Fibras na DietaRESUMO
Diclofenac is a commercial non-steroidal anti-inflammatory drug commonly present as a pollutant in naturally occurring water sources and wastewaters. In this work, the adsorption of diclofenac onto chitosan-coated magnetic nanosystems is proposed as a possible tool for remediation. Experimental and theoretical studies have been carried out to reveal the mechanisms associated with diclofenac interactions among all the components of the nanosystem. Mechanisms are presented, analyzed and discussed. A toxicological study in mice was carried out to evaluate the parameters associated with neurotoxicity of the nanodevice. The elucidation of the mechanisms implied in the adsorption process of diclofenac onto magnetic chitosan nanocomposites suggests that diclofenac remediation from water is possible by adsorption onto chitosan. The strategy innovates the commonly used methodologies for diclofenac remediation from pharmaceutical wastes. This magnetic nanotechnology would not induce damage on the nervous system in a murine model, in case of traces remaining in water sources.
Assuntos
Diclofenaco/análise , Recuperação e Remediação Ambiental/instrumentação , Nanotecnologia/instrumentação , Poluentes Químicos da Água/química , Poluição Química da Água/prevenção & controle , Adsorção , Anti-Inflamatórios não Esteroides/análise , Fenômenos Magnéticos , Águas Residuárias/análiseRESUMO
Pesticide exposure is associated with cognitive and psychomotor disorders. Glyphosate-based herbicides (GlyBH) are among the most used agrochemicals, and inhalation of GlyBH sprays may arise from frequent aerial pulverizations. Previously, we described that intranasal (IN) administration of GlyBH in mice decreases locomotor activity, increases anxiety, and impairs recognition memory. Then, the aim of the present study was to investigate the mechanisms involved in GlyBH neurotoxicity after IN administration. Adult male CF-1 mice were exposed to GlyBH IN administration (equivalent to 50 mg/kg/day of Gly acid, 3 days a week, during 4 weeks). Total thiol content and the activity of the enzymes catalase, acetylcholinesterase and transaminases were evaluated in different brain areas. In addition, markers of the cholinergic and the nigrostriatal pathways, as well as of astrocytes were evaluated by fluorescence microscopy in coronal brain sections. The brain areas chosen for analysis were those seen to be affected in our previous study. GlyBH IN administration impaired the redox balance of the brain and modified the activities of enzymes involved in cholinergic and glutamatergic pathways. Moreover, GlyBH treatment decreased the number of cholinergic neurons in the medial septum as well as the expression of the α7-acetylcholine receptor in the hippocampus. Also, the number of astrocytes increased in the anterior olfactory nucleus of the exposed mice. Taken together, these disturbances may contribute to the neurobehavioural impairments reported previously by us after IN GlyBH administration in mice.
Assuntos
Acetilcolina/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Glicina/análogos & derivados , Herbicidas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Administração Intranasal , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicina/administração & dosagem , Glicina/toxicidade , Herbicidas/administração & dosagem , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Vias Neurais/efeitos dos fármacos , Vias Neurais/metabolismo , Bulbo Olfatório/efeitos dos fármacos , Bulbo Olfatório/metabolismo , Oxirredução , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Compostos de Sulfidrila/metabolismo , Transaminases/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , GlifosatoRESUMO
Exposure to fluoride (F) during the development affects central nervous system of the offspring rats which results in the impairment of cognitive functions. However, the exact mechanisms of F neurotoxicity are not clearly defined. To investigate the effects of perinatal F exposure on memory ability of young rat offspring, dams were exposed to 5 and 10 mg/L F during gestation and lactation. Additionally, we evaluated the possible underlying neurotoxic mechanisms implicated. The results showed that the memory ability declined in 45-day-old offspring, together with a decrease of catalase and glutamate transaminases activity in specific brain areas. The present study reveals that exposure to F in early stages of rat development leads to impairment of memory in young offspring, highlighting the alterations of oxidative stress markers as well as the activity of enzymes involved in the glutamatergic system as a possible mechanisms of neurotoxicity.
Assuntos
Encéfalo/efeitos dos fármacos , Fluoretos/toxicidade , Troca Materno-Fetal , Memória/efeitos dos fármacos , Alquil e Aril Transferases/metabolismo , Animais , Animais Recém-Nascidos , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Encéfalo/metabolismo , Catalase/metabolismo , Feminino , Ácido Glutâmico/metabolismo , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Gravidez , Ratos Wistar , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismoRESUMO
Pregnant rats were treated with 0.3 and 0.6 mg cadmium (CdCl2)/kg injected subcutaneously on a daily basis from gestational day 7 to day 15 (organogenesis period). One control group was not injected and other received saline. The 45-day-old offspring were tested in a step-down inhibitory avoidance to evaluate short-term and long-term memory and in a radial maze for the study of spatial memory. These studies showed that gestational exposure to 0.6 mg Cd/kg produced in the male offspring a significant impairment in the retention of long-term memory evaluated 24 hours after training in the step-down inhibitory avoidance. The radial maze also demonstrated that the male offspring prenatally exposed to 0.6 mg Cd presented a significant deficit in the retention of spatial memory evaluated 42 days after training. These results demonstrate that the exposure to Cd during organogenesis may affect the retention of some types of memory.
Assuntos
Cádmio/toxicidade , Memória/efeitos dos fármacos , Efeitos Tardios da Exposição Pré-Natal , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Feminino , Masculino , Troca Materno-Fetal , Aprendizagem em Labirinto/efeitos dos fármacos , Gravidez , Ratos WistarRESUMO
Glyphosate-based herbicides (Gly-BHs) lead the world pesticide market. Although are frequently promoted as safe and of low toxicity, several investigations question its innocuousness. Previously, we described that oral exposure of rats to a Gly-BH during pregnancy and lactation decreased locomotor activity and anxiety in the offspring. The aim of the present study was to evaluate the mechanisms of neurotoxicity of this herbicide. Pregnant Wistar rats were supplied orally with 0.2 and 0.4% of Gly-BH (corresponding to 0.65 and 1.30 g/l of pure Gly, respectively) from gestational day (GD) 0, until weaning (postnatal day, PND, 21). Oxidative stress markers were determined in whole brain homogenates of PND90 offspring. The activity of acetylcholinesterase (AChE), transaminases, and alkaline phosphatase (AP) were assessed in prefrontal cortex (PFC), striatum, and hippocampus. Recognition memory was evaluated by the novel object recognition test. Brain antioxidant status was altered in Gly-BH-exposed rats. Moreover, AChE and transaminases activities were decreased and AP activity was increased in PFC, striatum and hippocampus by Gly-BH treatment. In addition, the recognition memory after 24 h was impaired in adult offspring perinatally exposed to Gly-BH. The present study reveals that exposure to a Gly-BH during early stages of rat development affects brain oxidative stress markers as well as the activity of enzymes involved in the glutamatergic and cholinergic systems. These alterations could contribute to the neurobehavioral variations reported previously by us, and to the impairment in recognition memory described in the present work.
Assuntos
Acetilcolina/metabolismo , Antioxidantes/metabolismo , Encéfalo/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Herbicidas/toxicidade , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Reconhecimento Psicológico/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Análise de Variância , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Feminino , Glutationa Peroxidase/metabolismo , Masculino , Malondialdeído/metabolismo , Gravidez , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
A simple two-step drug encapsulation method was developed to obtain biocompatible magnetic nanocarriers for the potential targeted treatment of diverse diseases. The nanodevice consists of a magnetite core coated with chitosan (Chit@MNPs) as a platform for diclofenac (Dic) loading as a model drug (Dic-Chit@MNPs). Mechanistic and experimental conditions related to drug incorporation and quantification are further addressed. This multi-disciplinary study aims to elucidate the toxicological impact of the MNPs at hematological, vascular, neurological and behavioral levels. Blood compatibility assays revealed that MNPs did not affect either erythrosedimentation rates or erythrocyte integrity at the evaluated doses (1, 10 and 100 µg mL-1). A microscopic evaluation of blood smears indicated that MNPs did not induce morphological changes in blood cells. Platelet aggregation was not affected by MNPs either and just a slight diminution was observed with Dic-Chit@MNPs, an effect possibly due to diclofenac. The examined formulations did not exert cytotoxicity on rat aortic endothelial cells and no changes in cell viability or their capacity to synthesize NO were observed. Behavioral and functional nervous system parameters in a functional observational battery were assessed after a subacute treatment of mice with Chit@MNPs. The urine pools of the exposed group were decreased. Nephritis and an increased number of megakaryocytes in the spleen were observed in the histopathological studies. Sub-acute exposure to Chit@MNPs did not produce significant changes in the parameters used to evaluate neurobehavioral toxicity. The aspects focused on within this manuscript are relevant at the pre-clinical level providing new and novel knowledge concerning the biocompatibility of magnetic nanodevices for biomedical applications.
Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Quitosana/toxicidade , Diclofenaco/administração & dosagem , Portadores de Fármacos/toxicidade , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Quitosana/química , Portadores de Fármacos/química , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Feminino , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/ultraestrutura , Camundongos , Óxido Nítrico/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Ratos WistarRESUMO
Chitosan coating on magnetic nanoparticles (MNPs) was studied on biological systems as a first step toward the application in the biomedical field as drug-targeted nanosystems. Composition of MNPs consists of magnetite functionalized with oleic acid and coated with the biopolymer chitosan or glutaraldehyde-cross-linked chitosan. The influence of the biopolymeric coating has been evaluated by in vitro and in vivo assays on the effects of these MNPs on rat aortic endothelial cells (ECs) viability and on the random tissue distribution in mice. Results were correlated with the physicochemical properties of the nanoparticles. Nitric oxide (NO) production by ECs was determined, considering that endothelial NO represents one of the major markers of ECs function. Cell viability was studied by MTT assay. Different doses of the MNPs (1, 10 and 100 µg/mL) were assayed, revealing that MNPs coated with non-cross-linked chitosan for 6 and 24 h did not affect neither NO production nor cell viability. However, a significant decrease in cell viability was observed after 36 h treatment with the highest dose of this nanocarrier. It was also revealed that the presence and dose of glutaraldehyde in the MNPs structureimpact on the cytotoxicity. The study of the acute tissue distribution was performed acutely in mice after 24 h of an intraperitoneal injection of the MNPs and sub acutely, after 28 days of weekly administration. Both formulations greatly avoided the initial clearance by the reticuloendothelial system (RES) in liver. Biological properties found for N1 and N2 in the performed assays reveal that chitosan coating improves biocompatibility of MNPs turning these magnetic nanosystems as promising devices for targeted drug delivery.
Assuntos
Quitosana/química , Células Endoteliais/efeitos dos fármacos , Nanopartículas de Magnetita/química , Animais , Sobrevivência Celular , Células Cultivadas , Portadores de Fármacos , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Excipientes , Feminino , Glutaral/química , Humanos , Camundongos , Óxido Nítrico/biossíntese , Ácido Oleico/química , Tamanho da Partícula , Ratos Wistar , Propriedades de Superfície , Distribuição TecidualRESUMO
Analgesic and ulcerogenic properties have been studied for the copper(II) coordination complex of the nonsteroidal anti-inflammatory drug Fenoprofen and imidazole [Cu(fen)2(im)2] (Cu: copper(II) ion; fen: fenoprofenate anion from Fenoprofen, im: imidazole). A therapeutic dose of 28 mg/kg was tested for [Cu(fen)2(im)2] and 21 mg/kg was employed for Fenoprofen calcium, administered by oral gavage in female mice to compare the therapeutic properties of the new entity. The acetic acid induced writhing test was employed to study visceral pain. The percentage of inhibition in writhing and stretching was 78.9% and 46.2% for the [Cu(fen)2(im)2] and Fenoprofen calcium, respectively. This result indicates that the complex could be more effective in diminishing visceral pain. The formalin test was evaluated to study the impact of the drugs over nociceptive and inflammatory pain. The complex is a more potent analgesic on inflammatory pain than the parent drug. Ulcerogenic effects were evaluated using a model of gastric lesions induced by hypothermic-restraint stress. Fenoprofen calcium salt caused an ulcer index of about 79 mm(2) while the one caused by [Cu(fen)2(im)2] was 22 mm(2). The complex diminished the development of gastric mucosal ulcers in comparison to the uncomplexed drug. Possible mechanisms of action related to both therapeutic properties have been discussed.