RESUMO
We conducted a rat exposure study to assess the impacts of dose and co-exposure with other rare earth elements (REEs) on the toxicokinetics of praseodymium (Pr) and cerium (Ce). We first determined the kinetic profiles of elemental Pr and Ce in blood, urine and feces along with tissue levels at sacrifice on the seventh day following intravenous injection of PrCl3 or CeCl3 at 0.3 or 1 mg/kg bw (of the chloride salts) in adult male Sprague-Dawley rats (n = 5 per group). In blood, Pr and Ce half-lives for the initial phase (t1/2α) increased with increasing doses, while their half-lives for the terminal phase (t1/2ß) were similar at both doses. In urine, a minor excretion route, no significant effect of the dose on the cumulative excretion was apparent. In feces, a major excretion route, the fraction of the Pr dose recovered was significantly lower at the 1 mg/kg bw dose compared to the 0.3 mg/kg bw dose, while no significant dose effect was apparent for Ce. In the liver and spleen, which are the main sites of REEs accumulation, there was a significant effect of the dose only for Ce retention in the spleen (i.e., increased retention of Ce in spleen at higher dose). Results were compared with those of a previous toxicokinetic study with a similar design but an exposure to a quaternary mixture of CeCl3, PrCl3, NdCl3 and YCl3, each administered at 0.3 mg/kg bw or 1 mg/kg bw. A mixture effect was apparent for the initial elimination phase (t1/2α) of Pr and Ce from blood and for the fecal excretion of Ce at the 1 mg/kg bw. In urine and liver, there was no evident overall mixture effect; in the spleen, there was a higher retention of Pr and Ce in rats exposed to the mixture at the 0.3 mg/kg bw, but not at the 1 mg/kg bw dose. Overall, this study showed that the dose and mixture exposure are two important factors to consider as determinants of the toxicokinetics of REEs.
Assuntos
Cério , Metais Terras Raras , Masculino , Ratos , Animais , Cério/toxicidade , Cério/urina , Praseodímio , Ratos Sprague-Dawley , Cloretos , Sais , ToxicocinéticaRESUMO
Permethrin (PER) is a pyrethroid pesticide that is extensively used as an insecticide in world because of its high activity and its low mammalian toxicity. The current study was conducted to investigate the protective action of Fumaria officinalis against PER-induced liver injury in male rats. However, HPLC-DAD showed the richness of 6 components in F. officinalis (F) including quercetin, ferulic acid, and naringenin which were the most abundant. Total polyphenols, total flavonoids, and condensed tannins were studied by phytochemical screening. In vitro, antioxidant properties showed that F. officinalis exhibited the highest DPPH radical, FRAP, and H2 O2 tests and total antioxidant capacity. Wistar rats were divided into four groups: negative control group (C), positive control group (F) (200 mg F. officinalis/kg BW), PER group (34.05 mg permethrin/kg BW), and PER + F group (34.05 mg permethrin/kg BW and 200 mg F. officinalis/kg BW). Oral administration of PER led to promote a decrease of body weight and Ca2+ -ATPases and Mg2+ -ATPases activities and an increase of plasma C-reactive protein level, transaminases, and hepatic Ï-GT activities as well as hepatic and mitochondrial oxidative stress. An increase in plasma lactate-to pyruvate ratio and a reduction in complexes enzymes I, III, and IV activities were also observed. In addition, histoarchitecture of liver in PER-treated rats showed apoptosis and necrosis as confirmed by DNA fragmentation. F. officinalis significantly exerted hepatoprotective effect by modulating hepatic alteration and mitochondrial dysfunction as well as genotoxicity. This effect could be attributed to phenolics compounds such as polyphenols, condensed tannins, and flavonoids.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Fumaria , Inseticidas , Permetrina , Proantocianidinas , Adenosina Trifosfatases/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose , Proteína C-Reativa/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Dano ao DNA , Flavonoides/farmacologia , Fumaria/química , Inseticidas/toxicidade , Lactatos/metabolismo , Fígado/metabolismo , Masculino , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo , Permetrina/toxicidade , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Polifenóis/farmacologia , Proantocianidinas/farmacologia , Piruvatos/farmacologia , Quercetina/farmacologia , Ratos , Ratos Wistar , TransaminasesRESUMO
BACKGROUND: Pyrethroids, such as bifenthrin (BF), are among the most widely used class of insecticides that pose serious risks to human and wildlife health. Pyrethroids are proposed to affect astrocytic functions and to cause neuron injury in the central nervous system (CNS). Microglia are key cells involved in innate immune responses in the CNS, and microglia activation has been linked to inflammation and neurotoxicity. However, little information is known about the effects of BF-induced toxicity in primary microglial cells as well as in organotypic hippocampal slice cultures (OHSCs). METHODS: Oxidative stress and inflammatory responses induced by BF were evaluated in primary microglial cells and OHSCs incubated with different concentrations of BF (1-20 µM) for 4 and 24 h. mRNA and protein synthesis of cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), nuclear erythroid-2 like factor-2 (Nrf-2), and microsomal prostaglandin synthase-1 (mPGES-1) was also studied by qPCR and Western blot. Cell viability was analyzed by MTT-tetrazolio (MTT) and lactate dehydrogenase (LDH) assays. Neurotoxicity in OHSCs was analyzed by propidium iodide (PI) staining and confocal microscopy. RESULTS: Exposure of microglial cells to BF for 24 h resulted in a dose-dependent reduction in the number of viable cells. At sub-cytotoxic concentrations, BF increased reactive oxygen species (ROS), TNF-alpha synthesis, and prostaglandin E2 (PGE2) production, at both 4- and 24-h time points, respectively. Furthermore, BF incubation decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and increased lipid peroxidation, protein oxidation, and H2O2 formation. In addition, BF significantly induced protein synthesis and mRNA expression of oxidative and inflammatory mediators after 4 and 24 h, including Nrf-2, COX-2, mPGES-1, and nuclear factor kappaB (NF-kappaB). A 24-h exposure of OHSCs to BF also increased neuronal death compared to untreated controls. Furthermore, depletion of microglia from OHSCs potently enhanced neuronal death induced by BF. CONCLUSIONS: Overall, BF exhibited cytotoxic effects in primary microglial cells, accompanied by the induction of various inflammatory and oxidative stress markers including the Nrf-2/COX-2/mPGES-1/NF-kappaB pathways. Moreover, the study provided evidence that BF induced neuronal death in OHSCs and suggests that microglia exert a protective function against BF toxicity.
Assuntos
Citocinas , Hipocampo , Inseticidas , Microglia , Piretrinas , Espécies Reativas de Oxigênio , Animais , Ratos , Animais Recém-Nascidos , Catalase/metabolismo , Células Cultivadas , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dinoprostona/metabolismo , Glutationa Peroxidase/metabolismo , Hipocampo/citologia , Técnicas In Vitro , Inseticidas/toxicidade , Peroxidação de Lipídeos/efeitos dos fármacos , Microglia/efeitos dos fármacos , Técnicas de Cultura de Órgãos , Piretrinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
Gliomas are the most common and malignant primary brain tumors. They are associated with a poor prognosis despite the availability of multiple therapeutic options. Naringin, a common dietary flavonoid abundantly present in fruits and vegetables, is believed to possess strong anti-proliferative and anti-cancer properties. However, there are no reports describing its effects on the invasion and migration of glioblastoma cell lines. Our results showed that the treatment of U251 glioma cell lines with different concentrations of naringin inhibited the invasion and migration of these cells. In addition, we revealed a decrease in the levels of matrix metalloproteinases (MMP-2) and (MMP-9) expression as well as proteinase activity in U251 glioma cells. In contrast, the expression of tissue inhibitor of metalloproteinases (TIMP-1) and (TIMP-2) was increased. Furthermore, naringin treatment decreased significantly the phosphorylated level of p38. Combined treatment with a p38 inhibitor (SB203580) resulted in the synergistic reduction of MMP-2 and MMP-9 expressions correlated with an increase of TIMP-1 and TIMP-2 expressions and the anti-invasive properties. However, p38 chemical activator (anisomycin) could block these effects produced by naringin, suggesting a direct downregulation of the p38 signaling pathway. These data suggest that naringin may have therapeutic potential for controlling invasiveness of malignant gliomas by inhibiting of p38 signal transduction pathways.
Assuntos
Movimento Celular/efeitos dos fármacos , Flavanonas/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Sinergismo Farmacológico , Inibidores Enzimáticos/farmacologia , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Imidazóis/farmacologia , Immunoblotting , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Invasividade Neoplásica , Fosforilação/efeitos dos fármacos , Piridinas/farmacologia , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
OBJECTIVE: This study aims to determine the systemic oxidant-antioxidant status in Tunisian patients with asthma. METHODS: We evaluated the levels of malondialdehyde (MDA) as thiobarbituric acid complexes, total protein carbonyls (PCs) and advanced oxidation protein products (AOPP). The levels of total thiols, protein sulfhydryls, glutathione (GSH), together with hydrogen peroxide, ascorbic acid, iron and total antioxidant status (TAS) were colorimetrically estimated. Glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities were assessed in plasma and erythrocytes by spectrophotometry. We also determined the levels of nitric oxide (NO) and peroxynitrite in plasma from asthmatic patients and healthy controls. The volume of fractionated exhaled NO (FeNO) was evaluated by the Medisoft HypAir method. Estimation of DNA damage was determined using the comet assay. RESULTS: Asthmatic patients showed increased levels of MDA in comparison to healthy controls (p < 0.001), while no significant difference was found in protein carbonyls (p = 0.79) and AOPP (p = 0.98). Patients with asthma also had significantly lower levels of total thiols (355.9 ± 15.72 versus 667.9 ± 22.65, p < 0.001), protein sulfhydryls (333.99 ± 16.41 versus 591.95 ± 24.28, p < 0.001) and glutathione (p < 0.001). They also showed decreased GSH-Px activity (p < 0.001), whereas no significant differences in measurements of catalase and SOD enzyme activities were observed between the two groups (respectively, p = 0.06 and p = 0.55). In addition, ascorbic acid and nitric oxide levels were decreased in asthmatics in comparison to controls (p < 0.01). CONCLUSIONS: Our findings highlight that oxidative stress and defective anti-oxidative status are major alterations in Tunisian patients with asthma.
Assuntos
Asma/fisiopatologia , Adulto , Produtos da Oxidação Avançada de Proteínas/metabolismo , Ácido Ascórbico/metabolismo , Asma/sangue , Biomarcadores , Catalase/metabolismo , Feminino , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Estresse Oxidativo/fisiologia , Carbonilação Proteica/fisiologia , Testes de Função Respiratória , Índice de Gravidade de Doença , Superóxido Dismutase/metabolismo , TunísiaRESUMO
Studies demonstrated that the iron chelating antioxidant restores brain dysfunction induced by iron toxicity in animals. Earlier, we found that iron overload-induced cerebral cortex apoptosis correlated with oxidative stress could be protected by naringenin (NGEN). In this respect, the present study is focused on the mechanisms associated with the protective efficacy of NGEN, natural flavonoid compound abundant in the peels of citrus fruit, on iron induced impairment of the anxiogenic-like behaviour, purinergic and cholinergic dysfunctions with oxidative stress related disorders on mitochondrial function in the rat hippocampus. Results showed that administration of NGEN (50 mg/kg/day) by gavage significantly ameliorated anxiogenic-like behaviour impairment induced by the exposure to 50 mg of Fe-dextran/kg/day intraperitoneally for 28 days in rats, decreased iron-induced reactive oxygen species formation and restored the iron-induced decrease of the acetylcholinesterase expression level, mitochondrial membrane potential and mitochondrial complexes activities in the hippocampus of rats. Moreover, NGEN was able to restore the alteration on the activity and expression of ectonucleotidases such as adenosine triphosphate diphosphohydrolase and 5'-nucleotidase, enzymes which hydrolyze and therefore control extracellular ATP and adenosine concentrations in the synaptic cleft. These results may contribute to a better understanding of the neuroprotective role of NGEN, emphasizing the influence of including this flavonoid in the diet for human health, possibly preventing brain injury associated with iron overload.
Assuntos
Acetilcolinesterase/metabolismo , Adenosina Trifosfatases/metabolismo , Ansiedade/metabolismo , Flavanonas/uso terapêutico , Hipocampo/metabolismo , Ferro/toxicidade , Animais , Ansiedade/induzido quimicamente , Ansiedade/tratamento farmacológico , Ativação Enzimática/efeitos dos fármacos , Ativação Enzimática/fisiologia , Flavanonas/farmacologia , Hipocampo/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Ratos , Ratos WistarRESUMO
Lambda-cyhalothrin (LTC) is a synthetic pyrethroid with a broad spectrum of insecticidal and acaricidal activities used to control a wide range of insect pests in a variety of applications. However, there is little known about its adverse effects, in particular those related to its genotoxicity in humans. To elucidate the genotoxicity mechanisms of LTC, the micronuclei (MN) frequencies, the levels of reactive oxygen species (ROS), erythrocyte osmotic fragility, nitrite (NO) formation, protein carbonyl (PCO) levels and malondialdehyde (MDA) production were evaluated for a period of 7, 14 and 21 days. Our results show that exposure rat to LTC (1/10DL50 = 6.23 mg/kg) for a period of 7, 14 and 21 days induced a noticeable genotoxic effect in rat peripheral blood evidenced by a significant increase in the frequency of MN only at day 21 of treatment. Significant differences between the two groups were observed in erythrocyte osmotic fragility. Further, a significant (p < 0.01) increase in ROS contents, NO formation, PCO levels and lipid peroxidation in erythrocytes were observed at different times of treatments, suggesting the implication of oxidative stress in its toxicity. These results confirm the genotoxic and the pro-oxidant effects of LTC in rat peripheral blood.
Assuntos
Dano ao DNA/efeitos dos fármacos , Inseticidas/toxicidade , Nitrilas/toxicidade , Piretrinas/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Animais , Eritrócitos/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído , Testes para Micronúcleos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica , Ratos , Ratos Wistar , Testes de ToxicidadeRESUMO
Background: The utilization of amorphous silica nanoparticles (SiNPs) is gaining popularity in various applications, but it poses a potential risk to human and environmental health. However, the underlying causes and mechanisms of SiNPs-induced kidney damage are still largely unknown. Objectives: This study aimed to investigate the SiNPs-induced damage in the kidney and further explore the possible mechanisms of SiNPs-induced nephrotoxicity. Methods: Thirty adult male rats were divided into 3 different groups. Rats in groups 2 and 3 were administered SiNPs at 2 dosage levels (25 and 100 mg/kg of body weight), while the rats in the control group received no treatment for 28 days. Reactive oxygen species (ROS), antioxidant enzyme activities (glutathione peroxidase [GPx], superoxide dismutase [SOD], and catalase [CAT]), glutathione (GSH) levels, and oxidation markers (such as lipid peroxidation [malondialdehyde (MDA)] and protein oxidation [protein carbonyl (PCO)]) were analyzed in the kidney tissue. Additionally, renal fibrogenesis was studied through histopathological examination and the expression levels of fibrotic biomarkers. Results: The findings revealed that in vivo treatment with SiNPs significantly triggered oxidative stress in kidney tissues in a dose-dependent manner. This was characterized by increased production of ROS, elevated levels of MDA, PCO, and nitric oxide (NO), along with a significant decline in the activities of SOD, CAT, GPx, and reduced GSH. These changes were consistent with the histopathological analysis, which indicated interstitial fibrosis with mononuclear inflammatory cell aggregation, tubular degeneration, glomerulonephritis, and glomerular atrophy. The fibrosis index was confirmed using Masson's trichrome staining. Additionally, there was a significant upregulation of fibrosis-related genes, including transforming growth factor-beta 1 (TGF-ß1), matrix metalloproteinases 2 and 9 (MMP-2/9), whereas the expression of tissue inhibitor of metalloproteinase 2 (TIMP2) was downregulated. Conclusions: This study provided a new research clue for the role of ROS and deregulated TGF-ß signaling pathway in SiNPs nephrotoxicity.
RESUMO
Prenatal stress (PS), in both humans and animals, presents a potential risk to the mother and her fetus throughout gestation. PS is always associated with physiological changes that alter embryonic development and predispose the individual to lifelong health problems, including susceptibility to mental illness. This study aims to identify the harmful effects of prenatal restraint stress (PRS), commonly employed to induce stress painlessly and without any lasting debilitation during gestation. This stress is applied to pregnant Swiss albino mice from E7.5 to delivery for three hours daily. Our results show that PS affects dams' weight gain during the gestational period; moreover, the PS dams prefer passive nursing, exhibit a lower percentage of licking and grooming, and impair other maternal behaviors, including nesting and pup retrieval. Concerning the offspring, this stress induces neurobehavioral impairments, including a significant increase in the time of recovery of the young stressed pups in the surface righting reflex, the latency to avoid the cliff in the cliff avoidance test, longer latencies to accomplish the task in negative geotaxis, and a lower score in swimming development. These alterations were accompanied by increased Malondialdehyde activity (MDA) at PND17 and 21 and downregulation of AchE activity in the whole brain of pups on postnatal days 7 and 9. These findings demonstrated that PS causes deleterious neurodevelopmental impairments that can alter various behaviors later in life.
Assuntos
Comportamento Materno , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal , Restrição Física , Estresse Psicológico , Animais , Gravidez , Feminino , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Camundongos , Estresse Psicológico/metabolismo , Estresse Psicológico/fisiopatologia , Estresse Oxidativo/fisiologia , Comportamento Materno/fisiologia , Malondialdeído/metabolismo , Animais Recém-Nascidos , Encéfalo/metabolismo , Masculino , Acetilcolinesterase/metabolismo , Comportamento Animal/fisiologia , Reflexo de Endireitamento/fisiologia , Aprendizagem da Esquiva/fisiologiaRESUMO
Corn and soybean oils are among the most frequently used vehicles for water-insoluble compounds in toxicological studies. These two vegetable oils are nutrients and may induce some biological effects on animals that might interfere with the experimental results. However, their chronic effects on a developing brain have not been reported. This study aims to evaluate the neurobehavioral and brain biochemical effects of both oils on male and female Swiss albino mice. Pregnant female mice were exposed to 1 µl/g/d of either tap water, corn oil (CO), or soybean oil (SO) from early gestation (GD1) until weaning then offspring mice were exposed to the same treatment regimen until adulthood (PND70). Our results showed that developmental exposure to both oils induced body weight changes in offspring mice. In addition, we detected some behavioral abnormalities where both oil-treated groups showed a significant decrease in locomotor activity and greater levels of anxiety behavior. Moreover, our results suggest that continuous exposure to these oils may alter motor coordination, spatial memory and induce depression-like behavior in adult mice. These alterations were accompanied by increased malondialdehyde, superoxide dismutase, and glutathione peroxidase activities in specific brain regions. Together, these data suggest that exposure to CO and SO as vehicles in developmental studies may interfere with the behavioral response and brain redox homeostasis in offspring mice.
Assuntos
Encéfalo , Óleo de Milho , Estresse Oxidativo , Efeitos Tardios da Exposição Pré-Natal , Óleo de Soja , Animais , Feminino , Óleo de Milho/administração & dosagem , Estresse Oxidativo/efeitos dos fármacos , Camundongos , Gravidez , Masculino , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Glutationa Peroxidase/metabolismo , Peso Corporal/efeitos dos fármacos , Malondialdeído/metabolismo , Superóxido Dismutase/metabolismo , Atividade Motora/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Ansiedade/induzido quimicamente , Aprendizagem em Labirinto/efeitos dos fármacos , Veículos FarmacêuticosRESUMO
Rare earth elements (REEs) are increasingly used in a wide range of applications. However, their toxicokinetic behaviors in animals and humans are not yet fully documented, hindering health risk assessments. We used a rat experimental model to provide novel data on the toxicokinetics of the insoluble oxide forms of praseodymium (Pr), neodymium (Nd), cerium (Ce) and yttrium (Y) administered intravenously. Detailed blood, urinary and fecal time courses were documented through serial sampling over 21 days in male Sprague-Dawley rats exposed to a mixture of these REE oxides administered at two different doses (0.3 or 1 mg kg-1 bw of each REE oxide commercially sold as bulk µm-sized particles). Tissue REE levels at the time of sacrifice were also measured. Significant effects of the dose on REE time courses in blood and on cumulative urinary and fecal excretion rates were observed for all four REE oxides assessed, as lower cumulative excretion rates were noted at the higher REE dose. In the liver, the main accumulation organ, the fraction of the administered REE dose remaining in the tissue at necropsy was similar at both doses. Toxicokinetic data for the REE oxides were compared to similar data for their chloride salts (also administered intravenously in a mixture, at 0.3 and 1 mg kg-1 bw of each REE chloride) obtained from a previous study. Compared to their chloride counterparts, faster elimination of REE oxides from the blood was observed in the first hours post-dosing. Furthermore, higher mean residence time (MRT) values as well as slower cumulative urinary and fecal excretion were determined for the REE oxides. Also, while liver REE retention was similar for both REE forms, the fractions of the administered REEs recovered in the spleen and lungs were noticeably higher for the REE oxides, at both dose levels. This study highlights the importance of both the dose and form of the administered REEs on their toxicokinetic profiles. Results indicate that chronic exposure and increased doses of REEs may favor bioaccumulation in the body, in particular for insoluble oxide forms of REEs, which are eliminated more slowly from the body.
Assuntos
Metais Terras Raras , Óxidos , Humanos , Masculino , Ratos , Animais , Óxidos/toxicidade , Toxicocinética , Cloretos , Ratos Sprague-Dawley , Metais Terras Raras/toxicidadeRESUMO
Glyphosate-based Herbicide (GBH) is a widely used pesticide that functions as a broad-spectrum, non-selective herbicide. Despite advanced research to describe the neurotoxic potential of GBH, the harmful effects on maternal behavior and neurodevelopment of offspring remain unclear. This study was conducted to highlight the effects of GBH on the antioxidant system, anxiety traits, social interaction, and cognitive and sensorimotor functions in pups exposed to 25 or 50 mg/l daily via their mother's milk. Concerning the biochemical biomarkers, GBH administered during the early stages of development negatively affected the status of antioxidant enzymes and lipid peroxidation in the brain structures of the pups. Furthermore, our results showed a significant decrease in acetylcholinesterase (AChE) specific activity within the brains of treated pups. The results of the behavioral tests indicated that the treated offspring developed anxiety, memory, and sociability disorders, as evidenced by the Open Field, Y-maze, object recognition task, and social interaction tests. Through neurodevelopmental testing, we also showed sensorimotor impairment (righting reflex and negative geotaxis) and abnormal maternal behavior. Altogether, our study clearly demonstrates that the developing brain is sensitive to GBH.
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The aim of this study was to evaluate the possible protective effects of Quercetin (Qe) against oxidative stress induced by λ cyhalothrin (LTC) in reproductive system. Thirty-two male rats were divided into four groups. First group was allocated as the control group. Second group was given a Qe alone while the third group received a LTC alone. Animals in the fourth group were given a Qe with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were determined in the testis. Additionally, the different histopathologic changes were observed in the testis of animals. LTC exposure significantly increased the abnormal morphology and LPO. On the contrary, sperm motility, viability and count, levels of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased compared to controls. Qe with LTC offset the decrease in functional sperm parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant levels when compared with LTC-treated rats. Furthermore, LTC showed irregular seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular seminiferous tubules showing spermatogenesis at level of spermatocytes. We conclude that LTC-induced oxidative stress and functional sperm parameters in male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to restore the antioxidant system and sperm parameters in male rats.
Assuntos
Antioxidantes/farmacologia , Inseticidas/toxicidade , Nitrilas/toxicidade , Piretrinas/toxicidade , Quercetina/farmacologia , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Animais , Catalase/metabolismo , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Túbulos Seminíferos/citologia , Túbulos Seminíferos/efeitos dos fármacos , Células de Sertoli/citologia , Células de Sertoli/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/metabolismo , Superóxido Dismutase/metabolismo , Testículo/citologia , Testículo/metabolismoRESUMO
Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Punicalagin (PU), the major ellagitannin found in pomegranates, is characterized by multiple antioxidant activities. The aim of this study is to assess the protective effects of PU against isoproterenol (ISO)-induced acute myocardial damage and to investigate its underlying vascular mechanisms using rat model. METHODS: Rats were randomly divided into five groups and were treated orally (p.o.) with PU (25 and 50 mg/kg) for 14 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 15th and 16th days to induce Myocardial infarction. Cardiac markers, oxidative stress markers, and inflammatory cytokines levels were determined in the heart tissue. Immunohistochemistry analysis was performed to determine the protein expression pathways of inflammation, apoptosis and oxidative stress (Nuclear factor erythroid 2-related factor 2 (Nrf-2), and heme oxygenase-1 (HO-1) in all the groups. In silico study was carried out to evaluate the molecular interaction of PU with some molecular targets. RESULTS: Our results showed that ISO-induced cardiac tissue injury was evidenced by increased serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH), associated with several histopathological changes. ISO also induced an increase of MDA, PCO, NO, and 8-hydroxy-2-deoxyguanosine (8-OHdG), along with a decrease of antioxidant enzyme activities in the myocardial tissues. In addition, an increase of TNF-α, NF-κB, IL-6, IL-1ß, iNOS, Nrf2 and (HO-1) was observed. Pre-treatment with PU reduced myocardial infract area, ameliorated histopathological alterations in myocardium, and decreased activities of myocardial injury marker enzymes in ISO-induced rats. In addition, PU remarkably restored ISO-induced elevation of lipid peroxidation and decrease of antioxidants, significantly reduced myocardial pro-inflammatory cytokines concentrations in this animal model. Molecular docking analysis of PU with protein targets showed potent interactions with negative binding energies. In conclusion, PU can protect the myocardium from oxidative injury, inflammatory response, and cell death induced by ISO by upregulating Nrf2/HO-1 signaling and antioxidants.
Assuntos
Taninos Hidrolisáveis , Infarto do Miocárdio , Ratos , Animais , Isoproterenol/toxicidade , Taninos Hidrolisáveis/farmacologia , Simulação de Acoplamento Molecular , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Fator 2 Relacionado a NF-E2/metabolismo , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/tratamento farmacológico , Miocárdio/metabolismo , Estresse Oxidativo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Citocinas/metabolismo , ApoptoseRESUMO
Manganese (Mn) is a potent neurotoxin involved in the initiation and progression of various cognitive disorders. Oxidative stress is reported as one of accepted mechanisms of Mn toxicity. The present study was designed to explore the effects of silymarin, a natural antioxidant, in attenuating the toxicity induced by Mn in rat cerebellum. In this investigation, rats were treated orally with MnCl2 (20 mg/ml) for 30 days, subsets of these animals were treated intraperitoneally daily with silymarin (100 mg/kg) along with respective controls. Mn exposure caused a marked oxidative stress in cerebellum as indicated by a significant decrease in the activities of enzymatic antioxidants like superoxide dismutase, catalase and glutathione peroxidase and in the levels of non-enzymatic antioxidants like reduced glutathione (GSH), total thiols and vitamin C. Conversely an increase was obtained in lipid and protein markers such as thiobarbituric reactive acid substances, lipid hydroperoxide and protein carbonyl products contents. A significant increase in acetylcholinesterase and a decrease in Naâº/Kâº-ATPase activities were also shown, with a substantial rise in the expression of acetylcholinesterase and inducible nitric oxide synthase (iNOS), and nitric oxide levels. The potential effect of SIL to prevent Mn induced neurotoxicity was also reflected by histopathological observations. Rats exposed to Mn showed a reduced number and morphological alterations of cerebellar Purkinje cells. These phenomenons were completely reversed by SIL co-treatment. We concluded that silymarin may protect against Mn-induced oxidative stress in cerebellum by inhibiting both lipid and protein oxidation and by activating acetylcholinesterase and inducible nitric oxide synthase (iNOS) gene expression.
Assuntos
Cerebelo/efeitos dos fármacos , Manganês/toxicidade , Silimarina/farmacologia , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/metabolismo , Sequência de Bases , Cerebelo/enzimologia , Cerebelo/metabolismo , Primers do DNA , Masculino , Oxirredução , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
This study investigated the protective effects of vanillin against acute brain damage induced by carbon tetrachloride (CCl4) in rats. The study was performed on 32 male rats divided into four groups: a control group, vanillin group ([Va] 150 mg/kg/day, intraperitoneally [i.p.]) and CCl4 toxication groups received a single injection of CCl4 (1 ml/kg, i.p.; CCl4 and Va + CCl4 groups). The degree of protection in brain tissue was evaluated by the levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase, glutathione transferase, glutathione peroxidase and nitric oxide (NO). Vanillin showed a significant brain-protective effect by decreasing the level of lipid peroxidation and NO2 and elevated the activities of antioxidative enzymes and level of GSH. Consequently vanillin blocked oxidative brain damage induced by CCl4 in rats.
Assuntos
Antioxidantes/farmacologia , Benzaldeídos/farmacologia , Química Encefálica/efeitos dos fármacos , Lesões Encefálicas/induzido quimicamente , Lesões Encefálicas/prevenção & controle , Tetracloreto de Carbono/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Acetilcolinesterase/metabolismo , Análise de Variância , Animais , Lesões Encefálicas/metabolismo , Glutationa Transferase/metabolismo , Masculino , Malondialdeído/análise , Óxido Nítrico/análise , Oxirredutases/metabolismo , Ratos , Ratos WistarRESUMO
The synthetic pyrethroids are expected to cause deleterious effects on most of the organs and especially on the male reproductive system. The current study was performed to assess the adverse effect of lambda cyhalothrin (LC) on reproductive organs and fertility in male rats and to evaluate the protective role of caffeic acid phenethyl ester (CAPE) in alleviating the detrimental effect of LC on male fertility. A total of 48 male rats were divided into 4 groups (12 rats each): control group received distilled water ad libitum and 1 ml of vehicle solution given intraperitoneally (i.p.); CAPE-treated group received a single i.p. dose of CAPE (10 µmol kg⻹ day⻹); LC-treated group received 668 ppm of LC through drinking water; and CAPE + LC-treated group received an i.p. injection of CAPE (10 µmol kg⻹ day⻹) 12 h before the LC administration. The experiment was conducted for 10 consecutive weeks. LC caused a significant increase in testicular malondialdehyde, catalase, superoxide dismutase, glutathione-S-transferase activities, and sperm abnormalities and a significant reduction in testicular glutathione concentration, sperm count, sperm motility, and a live sperm percentage. Conversely, treatment with CAPE improved the reduction in the sperm characteristics, LC-induced oxidative damage of testes and the testicular histopathological alterations. Results indicate that LC exerts significant harmful effects on the male reproductive system and that CAPE reduced the deleterious effects of LC on male fertility.
Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Nitrilas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Piretrinas/toxicidade , Espermatozoides/efeitos dos fármacos , Testículo/efeitos dos fármacos , Análise de Variância , Animais , Peso Corporal/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glutationa/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Álcool Feniletílico/farmacologia , Ratos , Ratos Wistar , Contagem de Espermatozoides , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Espermatozoides/patologia , Espermatozoides/fisiologia , Testículo/enzimologia , Testículo/metabolismo , Testículo/patologiaRESUMO
Owing to the presence of hemoglobin and polyunsaturated fatty acids, erythrocytes are a convenient model to understand membrane oxidative damage induced by various xenobiotic pro-oxidants. This study investigated the antioxidant activity of vanillin, a naturally occurring food-flavoring agent, against carbon tetrachloride (CCl(4))-induced erythrocyte damages in Wistar albino rats. A single injection of CCl(4) (1 ml/kg, intraperitoneally [i.p.]) caused a significant induction of oxidative damage as evidenced by increased thiobarbituric acid reactive substances, protein carbonyl levels and osmotic fragility accompanied with a significant decrease in Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities. Furthermore, catalase and superoxide dismutase activities were significantly elevated, while glutathione levels, glutathione-S-transferase and glutathione peroxidase activities were markedly reduced in the erythrocytes of CCl(4)-treated rats. Pretreatment of rats with vanillin (150 mg/kg/day, i.p.) for 3 consecutive days before CCl(4) injection protected erythrocytes against the increase of lipid peroxidation and degradation of membrane proteins compared to CCl(4)-treated rats and exhibited marked prevention against CCl(4)-induced oxidative stress, alterations of membrane-bound enzymes as well as erythrocyte osmotic fragility. Our results suggest that vanillin plays a protective and curative role against the harmful effects of CCl(4) on erythrocytes, thus ensuring membrane cell integrity.
Assuntos
Antioxidantes/farmacologia , Benzaldeídos/farmacologia , Tetracloreto de Carbono/toxicidade , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Adenosina Trifosfatases/efeitos dos fármacos , Animais , Eritrócitos/enzimologia , Testes Hematológicos , Hemólise/efeitos dos fármacos , L-Lactato Desidrogenase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Fragilidade Osmótica/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
The present study was designed to evaluate in vitro and in vivo the potential anti-inflammatory and nephroprotective potential of ethyl acetate fraction extracted from Fumaria officinalis (EAF) against permethrin (PER). Male wistar rats were treated daily by gavage during 7 days as follows: group C: negative control rats received 2 mL/kg bw of corn oil, group EAF: positive control rats received EAF at a dose of 200 mg/kg bw dissolved in water, group PER: rats received PER at a dose of 34.05 mg/kg bw and group (PER + EAF): rats received PER (34.05 mg/kg bw) and EAF (200 mg/kg bw). In vitro study showed the ability of EAF to inhibit protein denaturation and heat-induced hemolysis confirming its anti-inflammatory activity. In vivo, PER treatment decreased calcium (Ca) and phosphorus (P) levels and increased lactate dehydrogenase (LDH) activity in plasma. It induced oxidative stress objectified by an increase in the lipid peroxidation and protein oxidation and a perturbation of antioxidant system in kidney and mitochondria. The activities of NADH-ubiquinone reductase, ubiquinol-cytochrome C reductase and cytochrome C oxidase activities were reduced. These alterations were confirmed by histopathological studies. Co-treatment with EAF improved the antioxidant status and mitochondrial bioenergetics. The nephroprotective effects of EAF could be attributed to its modulation of detoxification enzymes and/or free radical scavenging actions.
Assuntos
Antioxidantes , Piretrinas , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cálcio/farmacologia , Óleo de Milho/farmacologia , Complexo III da Cadeia de Transporte de Elétrons/farmacologia , Complexo IV da Cadeia de Transporte de Elétrons , Flavonoides/farmacologia , Radicais Livres , Lactato Desidrogenases , Masculino , Mitocôndrias , NAD , Oxirredução , Estresse Oxidativo , Permetrina/farmacologia , Fósforo/farmacologia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Piretrinas/farmacologia , Ratos , Ratos Wistar , Ubiquinona/farmacologia , ÁguaRESUMO
Natural polyphenols are widely reported to have a large range of pharmacological properties, especially antioxidant activities and free radical scavenging capacities. In this study, we investigate the effects of naringin, chlorogenic acid, and quercetin mixtures (NCQ) on renal fibrosis in streptozotocin (STZ)-induced diabetic aged rats and its underlying mechanisms for ten consecutive weeks. The oxidative defense system in the kidneys of treated rats was found to be improved. Several biomarkers were investigated including the blood urea nitrogen, creatinine, and uric acid. Moreover, antioxidant parameters were evaluated and we found that superoxide dismutase, catalase, glutathione peroxidase, Na+-K+-ATPase activities, the nitric oxide production, the protein carbonyl, the advanced oxidation protein products, lipid peroxidation, and reduced glutathione levels were all significantly balanced and close to control values. In addition, NCQ restored renal injuries and fibrosis as assessed by histological method and molecular biology investigation of the matrix metalloproteinase, the transforming growth factor-beta TGF-ß, the tumor necrosis factor TNFα, and p53 expression. Our study proposes the NCQ combination as potential plant-derived bioactive compounds to prevent diabetic nephropathy.