RESUMO
The enteric nervous system (ENS) regulates several functional and immunological processes in the gastrointestinal tract. However, some diseases can disrupt the ENS functionality, impacting the behavior of enteric neurons and enteric glial cells by increasing the accumulation of reactive oxygen species. Oxidative stress is considered to be a trigger for alterations in these cells' morphology, density, and neurochemical patterns. In light of this, nutritional strategies are a growing field of investigation regarding their potential to modulate enteric neurons and enteric glial cells through reduced reactive oxygen species production. Moreover, several lines of evidence show that nutrients are related to counteracting oxidative stress. Some studies have evaluated the potential of nutrients with antioxidant roles (such as amino acids, polyphenols, prebiotics, vitamins, and specific extracts obtained from foods) to modulate the ENS. Thus, this review discusses how bioactive compounds and nutrients can impact the ENS by alleviating oxidative stress.
Assuntos
Antioxidantes , Sistema Nervoso Entérico , Aminoácidos , Antioxidantes/metabolismo , Encéfalo/metabolismo , Sistema Nervoso Entérico/metabolismo , Humanos , Nutrientes , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Vitaminas/metabolismoRESUMO
BACKGROUND: Toxoplasma gondii infection can occur through the ingestion of raw meat that contains tissue cysts or food that contains oocysts. Through the ingestion of oocysts, the parasite crosses the intestinal barrier, where the enteric nervous system is located. The objective was to investigate the kinetics of neuronal and glial responses during acute T. gondii infection. METHODS: We used 45 Wistar rats that were divided into a control group and infected groups that were evaluated at 6, 12, 24, 48, 72 hours, 7 days, 10 days, and 15 days after infection. The rats received 5000 sporulated oocysts of the parasite orally. To detect neurons and enteric glia cells, the myenteric and submucosal plexuses of the duodenum underwent double-labeling immunohistochemical techniques to evaluate HuC/HuD and S100, HuC/HuD and ChAT, and HuC/HuD and nNOS. KEY RESULTS: We observed a reduction of the total neuron population in the submucosal plexus 72 hours after infection. Cholinergic neurons decreased in the submucosal plexus 15 days after infection, and nitrergic neurons decreased in the myenteric plexus 72 hours after infection. A decrease in the number of glial cells was observed 7 days after infection in the submucosal plexus, and an increase in the enteric glial cell (EGC)/neuron ratio was found in both plexuses 48 hours after infection. CONCLUSIONS AND INFERENCES: We found decrease of neurons and increase in the EGC/neuron ratio in both plexuses caused by acute T. gondii infection, with major alterations 72 hours after oral infection. The number of cholinergic neurons decreased in the submucosal plexus, and the number of nitrergic neurons decreased in the myenteric plexus. A decrease in the number of enteric glial cells was observed in the submucosal plexus, and an increase in the enteric glial cell/neuron ratio was observed in both ganglionate plexuses of the duodenum.
Assuntos
Duodeno/patologia , Neuroglia/patologia , Neurônios/patologia , Toxoplasmose/patologia , Doença Aguda , Animais , Contagem de Células , Imuno-Histoquímica , Plexo Mientérico/patologia , Sistema Nervoso Parassimpático/patologia , Ratos , Ratos Wistar , Plexo Submucoso/patologiaRESUMO
BACKGROUND: Trypanosoma cruzi (T. cruzi) infects millions of Latin Americans each year and can induce chagasic megacolon. Little is known about how serotonin (5-HT) modulates this condition. Aim We investigated whether 5-HT synthesis alters T. cruzi infection in the colon. MATERIALS AND METHODS: Forty-eight paraffin-embedded samples from normal colon and chagasic megacolon were histopathologically analyzed (173/2009). Tryptophan hydroxylase 1 (Tph1) knockout (KO) mice and c-KitW-sh mice underwent T. cruzi infection together with their wild-type counterparts. Also, mice underwent different drug treatments (16.1.1064.60.3). RESULTS: In both humans and experimental mouse models, the serotonergic system was activated by T. cruzi infection (p < 0.05). While treating Tph1KO mice with 5-HT did not significantly increase parasitemia in the colon (p > 0.05), rescuing its synthesis promoted trypanosomiasis (p < 0.01). T. cruzi-related 5-HT release (p < 0.05) seemed not only to increase inflammatory signaling, but also to enlarge the pericryptal macrophage and mast cell populations (p < 0.01). Knocking out mast cells reduced trypanosomiasis (p < 0.01), although it did not further alter the neuroendocrine cell number and Tph1 expression (p > 0.05). Further experimentation revealed that pharmacologically inhibiting mast cell activity reduced colonic infection (p < 0.01). A similar finding was achieved when 5-HT synthesis was blocked in c-KitW-sh mice (p > 0.05). However, inhibiting mast cell activity in Tph1KO mice increased colonic trypanosomiasis (p < 0.01). CONCLUSION: We show that mast cells may modulate the T. cruzi-related increase of 5-HT synthesis in the intestinal colon.
Assuntos
Doença de Chagas/metabolismo , Colo/metabolismo , Enteropatias Parasitárias/metabolismo , Mastócitos/metabolismo , Megacolo/metabolismo , Serotonina/biossíntese , Trypanosoma cruzi/patogenicidade , Adulto , Idoso , Animais , Estudos de Casos e Controles , Doença de Chagas/genética , Doença de Chagas/parasitologia , Colo/parasitologia , Interações Hospedeiro-Patógeno , Humanos , Enteropatias Parasitárias/genética , Enteropatias Parasitárias/parasitologia , Masculino , Mastócitos/parasitologia , Megacolo/genética , Megacolo/parasitologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Fatores de Tempo , Triptofano Hidroxilase/genética , Triptofano Hidroxilase/metabolismoRESUMO
This study was designed to appraise the relationship between enteric neuropathy and oxidative stress in cancer cachexia under l-glutamine-supplemented diet. Total and nitrergic neuronal populations were investigated in jejunum and ileum in four experimental groups: control (C); control l-glutamine-supplemented diet (CG); Walker-256 tumor (TW); and Walker-256 tumor supplemented with l-glutamine (TWG). In addition, local oxidative stress, neuronal nitric oxide synthase (nNOS) enzyme and nitric oxide (NO) levels were evaluated. Neuronal density and somatic area of the total and nitrergic populations were reduced in TW rats, which was accompanied by high oxidative stress, NO and nNOS levels. l-glutamine supplementation prevented neuronal atrophy, changes in pan neuronal density and nNOS overexpression (ileum), and restored total antioxidant capacity. Nevertheless, the oxidative stress was partially mitigated and no effect was observed on the reduction of nitrergic population and NO levels. l-glutamine-supplemented diet extenuates NO-mediated damage on the myenteric plexus although has a small benefit on oxidative stress.
Assuntos
Carcinoma 256 de Walker/dietoterapia , Suplementos Nutricionais , Glutamina/administração & dosagem , Glutamina/farmacologia , Plexo Mientérico/efeitos dos fármacos , Óxido Nítrico/efeitos adversos , Animais , Antioxidantes , Caquexia/dietoterapia , Caquexia/metabolismo , Caquexia/patologia , Carcinoma 256 de Walker/patologia , Modelos Animais de Doenças , Glutamina/uso terapêutico , Íleo/efeitos dos fármacos , Íleo/metabolismo , Íleo/patologia , Jejuno/efeitos dos fármacos , Jejuno/metabolismo , Jejuno/patologia , Masculino , Neurônios , Óxido Nítrico Sintase Tipo I/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Carga Tumoral , terc-Butil Hidroperóxido/efeitos adversosRESUMO
The effects of quercetin supplementation in NADH-diaphorase positive (NADH-d) neurons of streptozotocin-induced diabetic rats was carried in this study. Fifteen male rats were divided into three groups: normoglycemic (N), diabetic (D) and diabetic supplemented with quercetin (DQ). Whole mount preparations of the muscular layer of the ileum underwent NADH-d histochemistry for evidencing the NADH-d neuronal subpopulation. Quantitative analyzes were performed on 30 random fields, and morphometric analyzes in 100 neuronal bodies and nuclei per animal. The supplementation promoted a 44 % reduction in the neuronal density in D group when compared to N group (p <0.001); a 24.5 % reduction was observed in the DQ group when compared to N (p <0.01). Animals in D group presented an 18.7 % increase in the cell body areas of myenteric neurons when compared to N (p <0.001); DQ group showed a 14.2 % decrease in neuronal areas when compared to D (p <0.01); the nuclear area were similar among the three groups. We conclude that quercetin supplementation was positive for animals with diabetes mellitus.
Se estudiaron los efectos de la suplementación con quercetina en neuronas NADH-diaforasa positiva (NADH-d) de ratas diabéticas inducidas por estreptozotocina. Quince ratas machos se dividieron en tres grupos: normoglicémico (N), diabéticos (D) y diabéticos suplementados con quercetina (DQ). Las cortes montados de la capa muscular del íleon fueron sometidos a histoquímica de NADH-d para evidenciar la subpoblación neuronal NADH-d. Se realizaron análisis cuantitativos en 30 campos aleatorios y análisis morfométricos en 100 cuerpos y núcleos neuronales, por animal. La suplementación promovió una reducción del 44 % en la densidad neuronal en el grupo D cuando se comparó con el grupo N (p <0,001). Se observó una reducción del 24,5 % en el grupo DQ en comparación con N (p <0,01). Los animales del grupo D presentaron un aumento del 18,7 % en las áreas del cuerpo celular de las neuronas mientéricas cuando se compararon con N (p <0,001). El grupo DQ mostró una disminución de 14,2 % en las áreas neuronales en comparación con D (p <0,01). El área nuclear fue similar entre los tres grupos. Se concluye que la suplementación con quercetina fue positiva para animales con diabetes mellitus.
Assuntos
Animais , Masculino , Ratos , Diabetes Mellitus Experimental , Íleo/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Quercetina/administração & dosagem , NADPH Desidrogenase , Ratos WistarRESUMO
Neste estudo, foram avaliados os efeitos da infecção crônica por taquizoítos de Toxoplasma gondii sobre os neurônios mientéricos do cólon descendente de ratos adultos. Utilizaram-se 10 ratos Wistar machos, com 60 dias de idade, divididos em grupo controle e experimental, que foram inoculados por via oral com 10(5) taquizoítos do genótipo I de T. gondii. Após 30 dias, os animais foram anestesiados e submetidos à laparatomia. O cólon descendente foi retirado, mensurado, dissecado e seus preparados de membrana submetidos à técnica de Giemsa, para coloração dos neurônios do plexo mientérico, seguido por análise morfométrica e quantitativa. Verificou-se que a infecção não causou alterações nas dimensões do órgão ou na população neuronal, porém houve um aumento significativo da área do pericário e citoplasma.
The effects of the chronic infection due to Toxoplasma gondii tachyzoites on the myenteric neurons of the adult rat descending colon were assessed in this study. Ten male, 60-day-old, Wistar rats, divided into control and experimental group were orally inoculated with 10(5) tachyzoites from Toxoplasma gondii genotype I strain. After 30 days, the animals were anesthetized and submitted to laparotomy. The descending colon was removed, dissected, and the whole-mounts were staining by Giemsa, in order to observe neurons of the myenteric plexus, followed by quantitative and morphometric analysis. It was verified that the infection caused alterations neither with respect to the dimensions of the organ nor the neuronal population; however, there was a significant increase of the perikarion area and the cytoplasm.
Assuntos
Animais , Masculino , Ratos , Colo/inervação , Plexo Mientérico/patologia , Toxoplasmose/complicações , Doença Crônica , Hipertrofia , Ratos WistarRESUMO
The effects of the chronic infection due to Toxoplasma gondii tachyzoites on the myenteric neurons of the adult rat descending colon were assessed in this study. Ten male, 60-day-old, Wistar rats, divided into control and experimental group were orally inoculated with 10(5) tachyzoites from Toxoplasma gondii genotype I strain. After 30 days, the animals were anesthetized and submitted to laparotomy. The descending colon was removed, dissected, and the whole-mounts were staining by Giemsa, in order to observe neurons of the myenteric plexus, followed by quantitative and morphometric analysis. It was verified that the infection caused alterations neither with respect to the dimensions of the organ nor the neuronal population; however, there was a significant increase of the perikarion area and the cytoplasm.
Neste estudo, foram avaliados os efeitos da infecção crônica por taquizoítos de Toxoplasma gondii sobre os neurônios mientéricos do cólon descendente de ratos adultos. Utilizaram-se 10 ratos Wistar machos, com 60 dias de idade, divididos em grupo controle e experimental, que foram inoculados por via oral com 10(5) taquizoítos do genótipo I de T. gondii. Após 30 dias, os animais foram anestesiados e submetidos à laparatomia. O cólon descendente foi retirado, mensurado, dissecado e seus preparados de membrana submetidos à técnica de Giemsa, para coloração dos neurônios do plexo mientérico, seguido por análise morfométrica e quantitativa. Verificou-se que a infecção não causou alterações nas dimensões do órgão ou na população neuronal, porém houve um aumento significativo da área do pericário e citoplasma.
RESUMO
The effects of protein malnutrition on the quantitative aspects of the myenteric plexus in the ileum of adult Rattus norvegicus were assessed. Thirty 90-day-old rats were divided into two groups: Control Group (CG, n=15) and Experimental Group (EG, n=15). The CG received 26 percent protein chow and the EG received 4 percent protein chow for 90 days. At the end of the experiment, the animals from the CG weighed 369.63±26.33, and the ones from the EG 215.34±56.31. The ileum was submitted to Giemsa, NADH- and NADPH-diaphorase technique in order to evidence nervous cells in the whole-mount preparations. Animals from the EG presented a 41.75 percent body weight loss in relation to the CG as well as 17.6 percent length reduction for the ileum-jejunum. Moreover, the organ was 41 percent lighter for the EG. Giemsa-stained neurons were 17.02 percent more concentrated in the EG (p>0.05). NADH-diaphorase-stained neurons were 26.6 percent more concentrated in the EG (p<0.05), while the NADPH-diaphorase were 26.28 percent more concentrated in this group (p<0.05).
Avaliou-se o efeito da desnutrição protéica sobre o número de neurônios mientéricos do íleo de ratos adultos. Foram utilizados 30 animais (90 dias de idade), divididos em dois grupos: controle (GC, n=15) e experimental (GE, n=15), sendo oferecido ao GC ração com teor protéico de 26 por cento e, para o GE, ração com 4 por cento de proteína, durante 90 dias. Os animais do grupo controle pesaram 369,63±26,33g e o experimental 215,34±56,31g. Preparados de membrana do íleo foram submetidos à técnica de Giemsa, NADH- e NADPH-diaforase. Os animais do GE apresentaram perda de peso de 41,75 por cento, em relação ao GC e redução do comprimento do jejuno-íleo de 17,6 por cento, além disso, o órgão apresentou-se 41 por cento mais leve no GE. Os neurônios corados com a técnica de Giemsa apresentaram-se 17,02 por cento mais concentrados no GE (p>0,05). Os neurônios NADH-diaforase apresentaram-se 26,60 por cento mais concentrados no GE (p<0,05). E os neurônios NADPH-diaforase apresentaram-se 26,28 por cento mais concentrados neste grupo (p<0,05).
Assuntos
Animais , Masculino , Ratos , Íleo/inervação , Plexo Mientérico/citologia , NADPH Desidrogenase/metabolismo , Neurônios/citologia , Deficiência de Proteína/metabolismo , Peso Corporal , Contagem de Células , Íleo/enzimologia , Plexo Mientérico/enzimologia , Neurônios/enzimologia , Tamanho do Órgão , Ratos WistarRESUMO
Objetivou-se avaliar os efeitos da desnutrição protéica sobre os aspectos morfológicos e quantitativos do plexo mientérico do colón ascendente de ratos adultos. Os animais controle (n=5) receberam ração comercial com 26% de proteína e os animais experimentais (n=4) ração com teor protéico reduzido para 4%, durante 90 dias. Por dissecção, elaboramos preparados totais, que foram corados pela técnica de Giemsa. Os ratos desnutridos apresentaram peso corporal 43,14% menor. A média da área do colón ascendente e a densidade neuronal estavam, respectivamente, 38,90% menor e 25,79% maior, em relação aos animais do grupo controle. Não foi observada redução no número total de neurônios mientéricos do cólon nos animais desnutridos. Dados morfométricos demonstraram aumento na área do pericário destes neurônios.
The effects of protein malnutrition on morphological and quantitative aspects of the myenteric plexus of adult rat ascending colon. The control animals (n=5) received 26%-protein commercial feed while the experimental (n=4) received 4%-protein commercial feed for 90 days. Whole mount preparations were Giemsa stained for dissection. Malnourished rats presented 43.14% lighter body weight. The means of the ascending colon area and the neuronal density were 38.90% lower and 25.79% higher, respectively, in relation to the Control Group. No reduction of the total number of colon myenteric neurons of malnourished animals was noticed. Morphometric data showed an increase of the perikarium of these neurons.
Esta investigación tuvo como objeto evaluar los efectos de la desnutrición proteica sobre los aspectos morfológicos y cuantitativos del plexo mientérico del colon ascendiente de ratones adultos. Los animales control (n=5) recibieron ración comercial con 26% de proteína y los animales experimentales (n=4) ración con tenor proteico reducido para 4%, durante 90 días. Por disección, elaboramos preparados totales, que fueron coloreados por la técnica de Giemsa. Los ratones desnutridos presentaron peso corporal 43,14% menor. La media del área del colon ascendiente y la densidad neuronal estaban, respectivamente, 38,90% menor y 25,79% mayor, en relación a los animales del grupo control. No fue observada reducción en el número total de neuronas del plexo mientérico del colon, en los animales desnutridos. Datos morfométricos demostraron aumento en el área del pericario de estas neuronas.
Assuntos
Animais , Colo Ascendente , Deficiência de Proteína , Dissecação , Neurônios , Plexo Mientérico/anatomia & histologia , RatosRESUMO
O objetivo deste estudo foi estudar os efeitos da desnutrição protéica e da carência de vitaminas do complexo B sobre o plexo mioentérico do colo ascendente de Rattus norvegicus. Vinte ratos foram divididos em dois grupos, sendo que, para um dos grupos foi oferecida ração com teor protéico de 22% (controle) e, para outro, ração com teor protéico de 8% com menor teor de vitaminas do complexo B, durante 120 dias. Coramos os preparados de membrana do colo ascendente pelo método de Giemsa e pela técnica da NADH-diaforase. Os ratos desnutridos apresentaram peso corporal 14,8% menor que o grupo controle, média da área do colo 54,2% menor, e a média da densidade neuronal foi 26,7% maior com a técnica de Giemsa e 27% com a técnica da NADH-diaforase. Como a redução da área não foi acompanhada por um aumento inversamente proporcional na densidade de neurônios, sugere-se que a condição imposta causou perda de neurônios mioentéricos.
This study was performed in order to study the effects of protein desnutrition and vitamin B complex deficiency on the myenteric plexus of the ascending colon of Rattus norvegicus. Twenty rats were divided into two groups; one had been fed with a 22%-protein-level ration, and the other with a 8%-protein-level without vitamin-B-complex supplementation, for 120 days. The whole-amounts of the ascending colon were stained with either Giemsa or NADH-diaphorase technique. The disnurtured rats showed a 14.8% smaller body weight than the control group, and the area of colon of the sample group was 54.2% smaller. The average neuronal density was 26.7% greater with the Giemsa technique and 27% greater with the NADH-diaphorase technique. As the decrease in area was not accompanied by an inversely proportional increase in neuronal density, it is suggested that the experimental condition led to a myenteric neuron loss.
El objetivo de este estudio fue analisar los efectos de la desnutrición proteica y de la carencia de vitaminas del complejo B sobre el plexo mioentérico del regazo ascendiente de Rattus norvegicus. Veinte ratones fueron divididos en dos grupos, siendo que, para uno de los grupos se ofreció ración con contenido proteico de 22% (control) y, para el otro, ración con contenido proteico de 8% con menor contenido de vitaminas del complejo B, durante 120 días. Coloreamos los preparados de membrana del regazo ascendiente por el método de Giemsa y por la técnica de la NADH-diaforasis. Los ratones desnutridos presentaron peso corporal 14,8% menor que el grupo control, promedio del área del regazo de 54,2% menor, y el promedio de la densidad neuronal fue 26,7% mayor con la técnica de Giemsa y 27% con la técnica de la NADH-diaforasis. Como la reducción del área no fue acompañada por un aumento inversamente proporcional en la densidad de neuronas, se cree que la condición impuesta causó pérdida de neuronas mioentéricos.