RESUMEN
Unhealthy dietary habits can play a crucial role in metabolic damages, promoting alteration of neural functions through the lifespan. Recently, dietary change has been perceived as the first line intervention in prevention and/or treatment of metabolic damages and related diseases. In this context, our study was designed to assess the eventual therapeutic effect of date seeds administration on memory and learning and on neuronal markers in a rat Metabolic Syndrome model. For this purpose, 32 adult male Wistar rats were fed with standard diet or high-fat high-sugar diet during ten weeks. After this, 16 rats were sacrified and the remaining rats received an oral administration of 300 mg of date seeds/kg of body weight during four supplementary weeks. Before sacrifice, we evaluate cognitive performances by the Barnes maze test. Afterwards, neuronal, astrocytic, microtubular and oxidative markers were investigated by immunoblotting methods. In Metabolic syndrome rats, results showed impairment of spatial memory and histological alterations. We identified neuronal damages in hippocampus, marked by a decrease of NeuN and an increase of GFAP and pTau396. Finally, we recorded an increase in protein oxidation and lipid peroxidation, respectively identified by an up-regulation of protein carbonyls and 4-HNe. Interestingly, date seeds administration improved these behavioural, histological, neuronal and oxidative damages highlighting the neuroprotective effect of this natural compound. Liquid Chromatography-Mass Spectrometry (LC-MS) identified, in date seeds, protocatechuic acid, caffeoylshikimic acid and vanillic acid, that could potentially prevent the progression of neurodegenerative diseases, acting through their antioxidant properties.
Asunto(s)
Síndrome Metabólico , Ratas , Masculino , Animales , Ratas Wistar , Síndrome Metabólico/complicaciones , Síndrome Metabólico/tratamiento farmacológico , Antioxidantes/uso terapéutico , Antioxidantes/farmacología , Estrés Oxidativo , SemillasRESUMEN
CONTEXT: Metabolic syndrome (MetS) is a clustering of several physiological alterations. OBJECTIVE: This study was designed to evaluate the effects of MetS on rats spermatogenesis and steroidogenesis. MATERIALS AND METHODS: We developed a MetS rodent model using high-sugar and high-fat diet. RESULTS: MetS rats showed severe disorders in sperm parameters. Interestingly, a significant increase in malondialdehyde level and a decrease in the antioxidant activities were observed. Moreover, qRT-PCR analysis showed Bax down-regulation and Bcl-2 up-regulation. A decrease in testosterone level was identified, correlated with the CYP11A1, CYP17A1 and 17ß HSD testicular marker down-regulation. Finally, MetS rats showed an up-regulation of pro-inflammatory cytokines receptors IL-1R and IL-6R. CONCLUSION: MetS induced severe testis toxicity in male rats. Mets markedly distorted sperm parameters, inhibited the transcription of steroidogenic enzymes and led to oxidative stress, inflammation, and alteration of Bax/Bcl-2 ratioin testicular tissues.
Asunto(s)
Síndrome Metabólico , Ratas , Masculino , Animales , Síndrome Metabólico/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Semen , Espermatogénesis , Testículo , Estrés Oxidativo , Testosterona/metabolismoRESUMEN
Electronic cigarettes (e-cigarettes) are devices intended to substitute conventional cigarettes, with the aim of being less harmful. In a previous report, we showed that intraperitoneal (i.p.) injection of e-cigarette liquid (E-liquid), with or without nicotine, induced toxicity in the testes of Wistar rats by disrupting oxidative balance and steroidogenesis. In the present work, we further evaluated the impact of e-liquid with or without nicotine on the epididymis of rats using the same procedure. Results showed that e-liquid treatments led to alteration of semen parameters, with a significant drop of at least 50% in sperm vitality, a significant increase of morphologically abnormal spermatozoa and an imbalance of redox status in comparison to the control group. A significant raise of 1.4 fold, compared to the untreated rats, in myeloperoxidase (MPO) granules after both treatments was recorded, suggesting an inflammatory state. Histopathological examination confirmed a marked reduction in sperm count in the cauda epididymis. Data of this study suggest that the pro-oxidant properties of e-liquid with or without nicotine, in addition to testicular defects, could lead to an inflammatory state in the epididymis, causing alterations in the semen parameters. These data provide additional information on the impact of e-liquid on the reproductive system.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Epidídimo/efectos de los fármacos , Agonistas Nicotínicos/toxicidad , Estrés Oxidativo/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Vapeo/efectos adversos , Animales , Supervivencia Celular/efectos de los fármacos , Epidídimo/metabolismo , Epidídimo/patología , Mediadores de Inflamación/metabolismo , Inyecciones Intraperitoneales , Masculino , Agonistas Nicotínicos/administración & dosificación , Peroxidasa/metabolismo , Ratas Wistar , Recuento de Espermatozoides , Espermatozoides/metabolismo , Espermatozoides/patología , Testosterona/sangreRESUMEN
Curcumin is a molecule found in turmeric root that has anti-inflammatory, antioxidant, and anti-tumor properties and has been widely used as both an herbal drug and a food additive to treat or prevent neurodegenerative diseases. This study aimed to investigate the effect of curcumin on neurobehavioral and neuropathological alterations induced by acetamiprid on male rats. Three groups of ten male Wistar rats each were used for the study: the first was a control group (CTR) that did not consume acetamiprid (ACE); the second was an experimental group (ACE) that consumed 40 mg/kg body weight/day of acetamiprid; and the third group (CUR) received curcumin (100 mg/kg) and acetamiprid (40 mg/kg) in combination. Neurobehavioral evaluations including inclined plane performance and forepaw grip time were studied. Treatment with CUR significantly prevented ACE-treated rats from impairments in the performance of neurobehavioral tests, indicating the presence of deficits on sensorimotor and neuromuscular responses. In addition, Curcumin administration protects rats against acetamiprid-induced cerebellum toxicity such as increase in AChE and BChE activities, decrease on cells viability, oxidative stress, and an increase of intracellular calcium. Taken together, these results demonstrate for the first time that ACE treatment substantially impairs the survival of primary neuronal cells through the induction of necrosis concomitantly with the generation of an oxidative stress. Additionally, curcumin reduced histopathological changes caused by ACE.
Asunto(s)
Conducta Animal/efectos de los fármacos , Cerebelo/efectos de los fármacos , Curcumina/farmacología , Neonicotinoides/toxicidad , Fármacos Neuroprotectores/farmacología , Síndromes de Neurotoxicidad/prevención & control , Estrés Oxidativo/efectos de los fármacos , Animales , Cerebelo/crecimiento & desarrollo , Cerebelo/metabolismo , Masculino , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Síndromes de Neurotoxicidad/metabolismo , Síndromes de Neurotoxicidad/patología , Ratas , Ratas WistarRESUMEN
This study was conducted to evaluate the effects of e-cigarette refill liquid administration alone or with nicotine on the antioxidant defense status, functional and histopathological changes in adult rat liver tissue. For this purpose, 32 rats were treated for 28 days as follows: control group was injected intra-peritoneally with physiological saline; e-cigarette 0% treated group received an intra-peritoneal injection of e-liquid without nicotine diluted in physiological saline, e-cigarette-treated group received an intra-peritoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline and nicotine-treated group received an intra-peritoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in physiological saline. In e-liquid without nicotine-exposed group, activities of the liver biomarkers aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase increase. Interestingly, oxidative stress indicators showed decreased total protein content, associated with a reduction in the antioxidant enzymes activities superoxide dismutase, catalase and glutathione-S-transferase, and an elevation in malondialdehyde content, highlighting the promotion of lipid peroxidation and oxidative stress. Histological studies identified inflammatory cells infiltration and cell death. Thus, e-liquid seems to promote oxidative tissue injuries, which in turn lead to the observed histopathological finding. In comparison, nicotine alone induced less oxidative stress and less histopathological disorders, whereas e-liquid with nicotine gave rise to more histopathological injuries. Thereby, e-liquid, per se, is able to induce hepatotoxicity and supplementation with nicotine worsens this state.
Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Nicotina/toxicidad , Estrés Oxidativo/efectos de los fármacos , Animales , Biomarcadores/sangre , Inyecciones Intraperitoneales , Hígado/enzimología , Hígado/patología , Pruebas de Función Hepática , Masculino , Nicotina/administración & dosificación , Tamaño de los Órganos/efectos de los fármacos , Ratas WistarRESUMEN
The present study was conducted to assess the toxic effect of e-cigarette refill liquid on cognitive and motor functions in adult rats. Animals were administered 28 µl/kg of body weight of e-liquid with/without a dose of 0.5 mg of nicotine/kg of body weight, using the intraperitoneally route for a period of 4 weeks. They were then evaluated by novel object recognition test (NORT) and spontaneous alternation T-maze test for cognitive functions. Results indicated that e-liquid without nicotine induced, in the NORT, a decrease in time exploring the novel object during the test session and lower discrimination and recognition indexes compared to control and e-liquid with nicotine treated rats. Furthermore, short-term spatial memory was affected after e-liquid treatment in the spontaneous alternation T-maze test, identifying recognition memory impairments. However, none of the treatments altered motor functions assessed by inclined plane test, Kondziela's inverted screen test and weights test. Cell cytotoxicity assessment following e-liquid exposure showed a significant decrease in hippocampal cell viability, but no change in cortical cell viability. Thereby, e-liquid without nicotine causes cognitive impairments, especially on the hippocampus. Based on these results, more extensive assessments on e-cigarettes must be carried out.
Asunto(s)
Conducta Animal/efectos de los fármacos , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Aprendizaje por Laberinto/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Nicotina/toxicidad , Reconocimiento Visual de Modelos/efectos de los fármacos , Animales , Cognición/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/patología , Inyecciones Intraperitoneales , Memoria a Corto Plazo/efectos de los fármacos , Actividad Motora/efectos de los fármacos , Nicotina/administración & dosificación , Ratas WistarRESUMEN
Electronic-cigarettes (e-cigarette), the alternative to classic cigarettes are becoming extremely popular but their safety is not still established. Recent studies have showed cytotoxic effects of the electronic cigarette and its recharge e-liquid, in vitro. The present study was designed to evaluate e-cigarette liquid nephrotoxicity in rats. For this purpose, 32 rats were treated for 28 days as follows: Control group was injected intraperitoneally with NaCl 9 g/l; e-cigarette 0% treated group received an intraperitoneal injection of e-liquid without nicotine diluted in NaCl 9 g/l, e-cigarette treated group, received an intraperitoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l and nicotine-treated group received an intraperitoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l. In nicotine group, creatinine level was increased, whereas urea and acid uric levels were decreased. In e-liquid-exposed groups, levels of uric acid and mainly urea were lower. Interestingly, after e-liquid exposure, oxidative stress status showed increased total protein and sulfhydril content, whereas superoxide dismutase and catalase activities were decreased. However, the levels of lipid peroxides were not increased after e-liquid exposure. Histological studies identified excess of cells with reduced and dark nuclei exclusively located in the renal collecting ducts. Thus, e-liquid seems to alter anti-oxidant defense and to promote minor changes in renal function parameters. This preliminary study raises some flags about possible nephrotoxicity of e-cigarette liquids in rats. As some features observed in rats may not be observed in human smokers, additional studies are needed to further qualify conclusions that might be applicable to actual users of e-cigarettes.
Asunto(s)
Lesión Renal Aguda/inducido químicamente , Sistemas Electrónicos de Liberación de Nicotina/efectos adversos , Riñón/efectos de los fármacos , Nicotina/toxicidad , Agonistas Nicotínicos/toxicidad , Cese del Hábito de Fumar/métodos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/patología , Lesión Renal Aguda/fisiopatología , Animales , Biomarcadores/sangre , Catalasa/metabolismo , Creatinina/sangre , Inyecciones Intraperitoneales , Riñón/metabolismo , Riñón/patología , Riñón/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Nicotina/administración & dosificación , Agonistas Nicotínicos/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Ratas Wistar , Medición de Riesgo , Especificidad de la Especie , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Pruebas de Toxicidad/métodos , Urea/sangre , Ácido Úrico/sangreRESUMEN
AIMS: Nicotine is known to promote body weight loss and to disturb glucose homeostasis and lipoprotein metabolism. Electronic cigarettes, as a substitute to nicotine, are becoming increasingly popular, although there is no evidence regarding their safety. Considering the dearth of information about e-cigarette toxicity, the present study was designed to compare nicotine alone to e-liquid with or without nicotine on metabolic parameters in Wistar rats. MAIN METHODS: For this purpose, e-liquid with or without nicotine and nicotine alone (0.5mg/kg of body weight) were administered intra-peritoneally during 28 days. KEY FINDINGS: Our results show a significant decrease in food and energy intake after nicotine or e-liquid with nicotine exposure, when compared to control or e-liquid without nicotine. Analysis of lipid status identified a significant decrease in cholesterol and LDL levels in e-cigarette groups, suggesting an improvement in lipid profile. Interestingly, e-liquid without nicotine induced hyperglycemia which is negatively correlated to hepatic glycogen level, acting like nicotine alone. Furthermore, an increase in liver biomarkers was observed in all treated groups. qRT-PCR analysis showed GSK3ß up-regulation in e-liquid with nicotine as well as, surprisingly, in e-liquid without nicotine exposure. In contrast, PEPCK genes were only up-regulated in e-liquid with nicotine. SIGNIFICANCE: While some features observed in rats may not be observed in human smokers, most of our data are consistent with, e-liquid per se i.e. without nicotine, not being neutral from a metabolic stand point since disrupting glucose homeostasis in rats.