A Rodent Model of Human-Dose-Equivalent 5-Fluorouracil: Toxicity in the Liver, Kidneys, and Lungs.

5-Fluorouracil (5-FU) is a chemotherapy drug widely used to treat a range of cancer types, despite the recurrence of adverse reactions. Therefore, information on its side effects when administered at a clinically recommended dose is relevant. On this basis, we examined the effects of the 5-FU clinical treatment on the integrity of the liver, kidneys, and lungs of rats. For this purpose, 14 male Wistar rats were divided into treated and control groups and 5-FU was administered at 15 mg/kg (4 consecutive days), 6 mg/kg (4 alternate days), and 15 mg/kg on the 14th day. On the 15th day, blood, liver, kidney, and lung samples were collected for histological, oxidative stress, and inflammatory evaluations. We observed a reduction in the antioxidant markers and an increase in lipid hydroperoxides (LOOH) in the liver of treated animals. We also detected elevated levels of inflammatory markers, histological lesions, apoptotic cells, and aspartate aminotransferase. Clinical treatment with 5-FU did not promote inflammatory or oxidative alterations in the kidney samples; however, histological and biochemical changes were observed, including increased serum urea and uric acid. 5-FU reduces endogenous antioxidant defenses and increases LOOH levels in the lungs, suggesting oxidative stress. Inflammation and histopathological alterations were also detected. The clinical protocol of 5-FU promotes toxicity in the liver, kidneys, and lungs of healthy rats, resulting in different levels of histological and biochemical alterations. These results will be useful in the search for new adjuvants to attenuate the adverse effects of 5-FU in such organs.

Global cerebral ischemia followed by long-term reperfusion promotes neurodegeneration, oxidative stress, and inflammation in the small intestine in Wistar rats.

AIMS: Brain ischemia and reperfusion may occur in several clinical conditions that have high rates of mortality and disability, compromising an individual's quality of life. Brain injury can affect organs beyond the brain, such as the gastrointestinal tract. The present study investigated the effects of cerebral ischemia on the ileum and jejunum during a chronic reperfusion period by examining oxidative stress, inflammatory parameters, and the myenteric plexus in Wistar rats. MAIN METHODS: Ischemia was induced by the four-vessel occlusion model for 15 min with 52 days of reperfusion. Oxidative stress and inflammatory markers were evaluated using biochemical techniques. Gastrointestinal transit time was evaluated, and immunofluorescence techniques were used to examine morpho-quantitative aspects of myenteric neurons. KEY FINDINGS: Brain ischemia and reperfusion promoted inflammation, characterized by increases in myeloperoxidase and N-acetylglycosaminidase activity, oxidative stress, and lipid hydroperoxides, decreases in superoxide dismutase and catalase activity, a decrease in levels of reduced glutathione, neurodegeneration in the gut, and slow gastrointestinal transit. SIGNIFICANCE: Chronic ischemia and reperfusion promoted a slow gastrointestinal transit time, oxidative stress, and inflammation and neurodegeneration in the small intestine in rats. These findings indicate that the use of antioxidant and antiinflammatory molecules even after a long period of reperfusion may be useful to alleviate the consequences of this pathology.

Neonatal metformin short exposure inhibits male reproductive dysfunction caused by a high-fat diet in adult rats.

Metformin (Met) is widely used to control blood glucose levels and acts on various organs, including reproductive tissues, to improve reproductive and lifespan. This study evaluated whether neonatal Met exposure prevented male reproductive dysfunction caused by being overweight during adulthood. Randomized Wistar rat pups received an intraperitoneal injection from postnatal days (PNDs) 1 to 12of saline (Sal; 0.9% NaCl/day in 2mL/kg) or Met (100 mg/kg/day in 2 mL/kg). From PNDs 60 to 90, the animals received a regular (R; 4.5% fat; Sal R and Met R groups) or a high-fat (HF; 35% fat; Sal HF and Met HF groups) diet. At PND 90, all animals were euthanized to evaluate their biometric and reproductive parameters. The Sal and Met groups with R showed similar body weights, however, the HF diet increased the body weight in both groups. The Sal HF group showed testicular damage regarding in antioxidant status and inflammatory profile in the epididymal cauda. The HF diet reduced Leydig and Sertoli cells numbers, with lower sperm quality. The Met R animals showed positive reproductive programming, due to improved antioxidant defense, inflammatory biomarkers, and sperm morphology. Met HF prevented HF diet damage to reproductive organs and sperm morphology, but not to sperm motility. Early Met exposure positively affected the male reproductive system of adult rats, preventing reproductive HF disorders. STATEMENT OF NOVELTY AND SIGNIFICANCE: Metformin is used to control type 2 diabetes mellitus and can act to improve metabolism and lifespan. Metformin avoidance is recommended during pregnancy, but there is no information regarding its use when breastfeeding. For the first time, we showed in this current study that metformin positively acts in the male reproductive tissues and helps involved in later life. These data showed a better antioxidant defense and anti-inflammatory profile of Metformin animals than Saline animals and might directly improve reproductive organs morphophysiology and sperm morphology. Also, the neonatal Met application programs the male reproduction to counterbalance damages from an obesogenic environment in later life.

Colonic neuronal loss and delayed motility induced by high-fat diet occur independently of changes in the major groups of microbiota in Swiss mice.

BACKGROUND: Obesity has been linked to gastrointestinal disorders, and the loss of myenteric neurons in the intestine caused by high-fat diets (HFD) has been attributed to changes in microbiota and lipotoxicity. We investigated whether the prebiotic inulin modulates bacterial populations and alleviates neuronal loss in mice fed HFD. METHODS: Swiss mice were fed purified rodent diet or HFD (59% kcal fat), or both diets supplemented with inulin for 17 weeks. Intestinal motility was assessed and a metagenome analysis of the colonic microbiota was performed. The gene expression of inflammatory markers was evaluated, and immunofluorescence was performed for different types of myenteric neurons and glial cells in the distal colon. KEY RESULTS: The HFD caused obesity and delayed colonic motility. The loss of myenteric neurons and glial cells in obese mice affected all of the studied neuronal populations, including neurons positive for myosin-V, neuronal nitric oxide synthase, vasoactive intestinal peptide, and calretinin. Although obese mice supplemented with inulin exhibited improvements in colonic motility, neuronal, and glial cell loss persisted. The HFD did not altered the expression levels of inflammatory cytokines in the intestine or the prevalence of the major groups in microbiota, but inulin increased the proportion of the genus Akkermansia in the obese mice. CONCLUSIONS AND INFERENCES: In Swiss mice, the HFD-induced neuronal loss but did not change the major groups in microbiota. This suggests that, despite the increase in the beneficial bacteria, other factors that are directly linked to excess dietary lipid intake affect the enteric nervous system.

Chronic ingestion of deoxynivalenol-contaminated diet dose-dependently decreases the area of myenteric neurons and gliocytes of rats.

BACKGROUND: Deoxynivalenol (DON), a mycotoxin produced by Fusarium spp., is commonly found in cereals ingested by humans and animals. Its ingestion is correlated with hepatic, hematologic, renal, splenic, cardiac, gastrointestinal, and neural damages, according to dose, duration of exposure and species. In this work, the effects of the ingestion of DON-contaminated diet at concentrations considered tolerable for human and animal intake were assessed. METHODS: Male Wistar rats aging 21 days were allotted to five groups that were given, for 42 days, diets contaminated with different concentrations of DON (0, 0.2, 0.75, 1.75, and 2 mg kg-1 of chow). Food ingestion, bodyweight, oxidative status and morphometric analyses of gliocytes, and neurons of jejunal myenteric ganglia were recorded. KEY RESULTS: At these concentrations, there was no food rejection, decrease in bodyweight gain, changes in oxidative status, or loss of either neurons or gliocytes. However, DON decreased gliocyte area, general neuronal population, nitrergic, cholinergic and NADH-diaphorase positive subpopulations and, as a result, ganglion area. CONCLUSIONS & INFERENCES: It was concluded that, even in the absence of visible effect, DON exposure reduces cell body area of gliocytes and neurons of the myenteric plexus of the rat jejunum.

Curcumin protects remote organs against injury that is caused by intestinal ischemia and reperfusion

In addition to several local pathophysiological consequences, intestinal injury that is caused by ischemia and reperfusion can result in the development of lesions in remote organs. Curcumin has therapeutic potential because of its antiinflammatory and antioxidant effects. The present study evaluated the effects of curcumin on oxidative and inflammatory parameters in the liver and kidneys in rats that were subjected to intestinal ischemia and reperfusion. The rats were subjected to 45 min. of ischemia followed by 7 days of reperfusion and treated daily with 60 mg kg-1 curcumin. The liver and kidneys were collected, weighed, and biochemically analyzed. Intestinal ischemia and reperfusion increased levels of lipid hydroperoxide (LOOH), decreased levels of reduced glutathione (GSH), and increased the enzymatic activity of superoxide dismutase (SOD), glutathione S-transferase (GST), and myeloperoxidase (MPO) in the liver. Intestinal ischemia and reperfusion decreased kidney weight and increased GST activity in the kidneys. Curcumin prevented these changes in the liver and kidneys. Intestinal ischemia and reperfusion mainly affected the liver, promoting inflammation and oxidative stress. The kidneys underwent repair much earlier than the liver, in which they did not present alterations of MPO or main parameters of oxidative stress after 7 days of reperfusion. Treatment with curcumin had beneficial effects, ameliorating or even preventing injury that was caused by intestinal ischemia and reperfusion in the liver and kidneys in rats

Resveratrol promotes neuroprotection and attenuates oxidative and nitrosative stress in the small intestine in diabetic rats.

Damages to the enteric nervous system caused by diabetes mellitus (DM) are frequently attributed to oxidative and nitrosative stress. We aimed to investigate the effect of Resveratrol (RSV) (10 mg/kg) on oxidative and nitrosative stress in the intestinal wall and morphoquantitative aspects of the myenteric plexus of the duodenum, jejunum and ileum in diabetic rats. Twenty-four rats were distributed into four groups (n = 6/group): control (C group), control treated with RSV (CR group), diabetic (D group), and diabetic treated with RSV (DR group) for 120 days. Immunohistochemical staining techniques for the general neuronal population, nitrergic and calretinin neuronal subpopulations, enteric glial cells and glial fibrillary acid protein were performed in the myenteric plexus. Furthermore, parameters of oxidative and nitrosative stress were analyzed in the intestinal wall. RSV attenuated oxidative and nitrosative stress and prevented neuronal loss and hypertrophy of the HuC/D-IR, nNOS-IR and CALR-IR neuronal subpopulations in the DR group compared with the D group (P < 0.05). In addition, RSV prevented the increase in glial fibrillary acid protein fluorescence in the DR group compared with the D (P < 0.05). These results suggest that RSV has antioxidant and neuroprotective effects in myenteric plexus in rats with experimental DM.

Evaluation of the treatment with resveratrol-loaded nanoparticles in intestinal injury model caused by ischemia and reperfusion.

The gastrointestinal tract is extremely sensitive to ischemia and reperfusion (I/R). Studies have reported that resveratrol (RSV) is able to combat damage caused by intestinal I/R. Because of its effectiveness in increasing the permanence and bioavailability of resveratrol in the intestinal epithelium, we investigated whether the effect of resveratrol-loaded in poly(anhydride) nanoparticles reduce oxidative stress and promote myenteric neuroprotection in the ileum of rats subjected to I/R. Physicochemical evaluations were performed on nanoparticles. The animals were divided into nine groups (n = 6/group) and treated every 48 h. Treatments with resveratrol (7 mg/kg of body weight) were applied 5 days before surgery and continued for 7 days after surgery (reperfusion period). The superior mesenteric artery was occluded to cause I/R injury. Oxidative stress, myeloperoxidase, nitrite, aspartate aminotransferase, alanine aminotransferase, immunolabeling of myenteric neurons and glial cells, and gastrointestinal transit was evaluated. Both nanoparticle formulations presented negative charge with homogeneous distribution, and the payload, showed an encapsulation efficiency of 60%. Resveratrol administered in free form prevented alterations that were caused by I/R. The results of the groups treated with RSV-loaded nanoparticles presented similar results to the group treated with free resveratrol. Treatment with empty nanoparticles showed that poly(anhydride) is not an ideal nanocarrier for application in in vivo models of intestinal I/R injury, because of hepatotoxicity that may be caused by epithelial barrier dysfunction that triggers the translocation of nanoparticles.

Effect of simvastatin on sensorial, motor, and morphological parameters in sciatic nerve crush induced-neuropathic pain in rats.

The present study compares the effects of a low and high doses of simvastatin in a model of peripheral neuropathy by evaluating sensorial, motor, and morphological parameters. First, male Wistar rats were orally treated with vehicle (saline, 1 mL/kg), simvastatin (2 and 80 mg/kg) or morphine (2 mg/kg, s.c.), 1 h before 2.5% formalin injection. Neuropathic pain was induced by crushing the sciatic nerve, and mechanical and cold allodynia, nerve function, histology, MPO and NAG concentrations, as well as mevalonate induced-nociception were evaluated. Animals were orally treated with vehicle, simvastatin, or gabapentin (30 mg/kg) for 18 days. Simvastatin (2 and 80 mg/kg) reduced the inflammatory pain induced by formalin, but failed to decrease the paw edema. Mechanical allodynia was reduced by the simvastatin (2 mg/kg) until the 12th day after injury and until the 18th day by gabapentin. However, both simvastatin and gabapentin treatments failed in attenuated cold allodynia or improved motor function. Interestingly, both doses of simvastatin showed a neuroprotective effect and inhibited MPO activity without altering kidney and hepatic parameters. Additionally, only the higher dose of simvastatin reduced the cholesterol levels and the nociception induced by mevalonate. Our results reinforce the antinociceptive, antiallodynic, and anti-inflammatory effects of oral simvastatin administration, which can strongly contribute to the sciatic nerve morphology preservation. Furthermore, our data suggest that lower and higher doses of simvastatin present beneficial effects that are dependent and independent of the mevalonate pathway, respectively, without causing signs of nerve damage.

Resveratrol promotes myenteric neuroprotection in the ileum of rats after ischemia-reperfusion injury.

AIMS: The present study evaluated the effects of resveratrol in the myenteric plexus after intestinal ischemia-reperfusion (I/R) injury caused by occluding the superior mesenteric artery for 45min, followed by 7days of reperfusion. MAIN METHODS: Forty-two male Wistar rats were divided into seven groups: control (C group), untreated sham surgery control (SC group), sham surgery control treated with resveratrol before surgery (STA group), sham surgery control treated with resveratrol before and after surgery (STAD group), ischemic control (IRC group), ischemic treated before I/R (IRTA group), and ischemic treated before and after I/R (IRTAD group). Resveratrol (10mg/kg) was administered for 4days and 2h prior to surgery and/or 7days later. Morphometric analyses were performed, and the density of the general neuronal population (HuC/D-immunoreactive [IR]), nitrergic subpopulation (neuronal nitric oxide synthase [nNOS]-IR), vasoactive intestinal peptide (VIP)ergic varicosities (VIP-IR), and glial cells (S100-IR) was determined. KEY FINDINGS: Injury that was caused by I/R significantly reduced (p<0.01) the HuC/D-IR general neuronal population. Treatment with resveratrol before and after ischemia had a neuroprotective effect. Morphometric changes caused by I/R in nitrergic neurons and varicosities were also attenuated by resveratrol. Ischemia/reperfusion promoted the proliferation of enteric glial cells, and resveratrol treatment before and after I/R reversed this effect. SIGNIFICANCE: Resveratrol had neuroprotective effects, showing promise for application in intestinal surgery and transplants.

Trypanosoma cruzi (CEPA CL) promove perda neuronal no plexo mioentérico do cólon de ratos / Trypanosoma cruzi (STRAIN CL) causes neuronal loss in rats´ myo-enteric plexus of the colon

Trypanosoma cruzi, um protozoário parasita, é o agente etiológico da doença de Chagas. A infecção chagásica apresenta duas fases: aguda e crônica. Na fase aguda a mortalidade é mais frequente, sendo que o organismo que consegue sobreviver a ela passa para a fase crônica indeterminada. No trato gastrointestinal o T. gondii pode parasitar o sistema nervoso intramural formando os megaesôfago e o megacólon. Não existem trabalhos que relacionam a perda neuronal do plexo mientérico com a infecção com a cepa CL do T. cruzi. Portanto, o objetivo deste trabalho foi verificar alterações morfoquantitativas no plexo mioentérico no colo distal de ratos infectados com a cepa CL durante a fase aguda e crônica da doença. Foram utilizados 20 ratos divididos em quatro grupos: infectado com a cepa CL durante 7 dias (grupo IA) do T. cruzi e seu controle (grupo CA), ambos sacrificados após sete dias do início do experimento, outro grupo infectado (IC) e sacrificado após trinta dias e seu controle (CC). Foi realizada a estimativa da densidade neuronal e a morfometria das áreas do perfil dos corpos celulares dos neurônios através da técnica de Giemsa. A análise quantitativa demonstrou uma redução significativa no número de neurônios nos grupos infectados IA e IC. Em relação ao perfil neuronal foi observada uma atrofia dos neurônios do grupo IC em relação ao controle. Portanto, a cepa CL do T. cruzi provoca uma denervação do plexo mioentérico do colo sem contudo ocasionar hipertrofia neuronal no tempo experimental de trinta dias.

The parasite protozoa Trypanosoma cruzi is the etiological agent of Chagas´s disease. Infection comprises the acute and chronic type. Mortality in the former is more frequent and the organism that survives passes to the undetermined chronic phase. T. gondii within the gastrointestinal tract parasites the intramural nervous system and causes mega-esophagus and mega-colon. No reports in the literature relate neuronal loss of the myo-enteric plexus with infection by strain CL of T. cruzi. Current analysis verifies morphoquantitative alterations in the myo-enteric plexus in rats´ distal colon infected with strain CL during the acute and chronic phase of the disease. Twenty rats were divided into four groups: infected with strain CL of T. cruzi during 7 days (Group IA) and its control (Group CA), killed after seven days from the start of the experiment; another infected group (IC), killed after 30 days and its control (CC). Neuronal density and morphometry of the areas of cell bodies of neurons were estimated by Giemsa technique. Quantitative analysis showed a significant decrease in the number of neurons in infected groups IA and IC. In the case of the neuronal profile, atrophy of neurons of group IC was reported when compared to control. Strain CL of T. cruzi causes a de-nerving of the myo-enteric plexus of the colon without causing a neuronal hypertrophy during the thirty days of experimental period.

Resveratrol Reduces Morphologic Changes in the Myenteric Plexus and Oxidative Stress in the Ileum in Rats with Ischemia/Reperfusion Injury.

BACKGROUND: Intestinal ischemia/reperfusion injury can be caused by surgical procedures and inflammatory bowel disease. It is normally associated with the increased production of free radicals and changes in the enteric nervous system. AIMS: Given the antioxidant and neuroprotective properties of resveratrol, the present study assessed its influence on oxidative stress in the intestinal wall and the morphology of myenteric neurons in the ileum of rats subjected to ischemia/reperfusion. METHODS: Resveratrol was orally administered daily at a dose of 10 mg/kg for 5 days. Changes in the ileum response to ischemia after 45 min were investigated followed by 3 h reperfusion. Lipoperoxide and carbonylated protein levels, and the activity of the antioxidant enzymes glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase were measured following ischemia/reperfusion injury. RESULTS: The density and morphometry of the general neuronal population, nitrergic neurons and glial cells, and morphometry of VIP varicosities in the ileum were also studied. Lipoperoxide and carbonylated protein levels were 171 and 40% higher during the ischemia/reperfusion, respectively, compared to control cohorts, and resveratrol attenuated these values. The glutathione ratio was 64% lower during ischemia/reperfusion, compared to control cohorts. Resveratrol increased the reduced/oxidized glutathione ratio, attenuated the changes in the activity of the antioxidant enzymes and the detrimental morphologic changes caused by ischemia/reperfusion in the general neuronal population and nitrergic neurons. CONCLUSIONS: Oral treatment with resveratrol reduced the oxidative stress in the ileum and attenuated the morphologic changes that occurred in the myenteric plexus of the ileum in rats subjected to ischemia/reperfusion.

Aqueous Extract of Agaricus blazei Murrill Prevents Age-Related Changes in the Myenteric Plexus of the Jejunum in Rats.

This study evaluated the effects of the supplementation with aqueous extract of Agaricus blazei Murrill (ABM) on biometric and blood parameters and quantitative morphology of the myenteric plexus and jejunal wall in aging Wistar rats. The animals were euthanized at 7 (C7), 12 (C12 and CA12), and 23 months of age (C23 and CA23). The CA12 and CA23 groups received a daily dose of ABM extract (26 mg/animal) via gavage, beginning at 7 months of age. A reduction in food intake was observed with aging, with increases in the Lee index, retroperitoneal fat, intestinal length, and levels of total cholesterol and total proteins. Aging led to a reduction of the total wall thickness, mucosa tunic, villus height, crypt depth, and number of goblet cells. In the myenteric plexus, aging quantitatively decreased the population of HuC/D(+) neuronal and S100(+) glial cells, with maintenance of the nNOS(+) nitrergic subpopulation and increase in the cell body area of these populations. Supplementation with the ABM extract preserved the myenteric plexus in old animals, in which no differences were detected in the density and cell body profile of neurons and glial cells in the CA12 and CA23 groups, compared with C7 group. The supplementation with the aqueous extract of ABM efficiently maintained myenteric plexus homeostasis, which positively influenced the physiology and prevented the death of the neurons and glial cells.

Intestinal and neuronal myenteric adaptations in the small intestine induced by a high-fat diet in mice.

BACKGROUND: The prevalence of obesity has increased at alarming rates, particularly because of the increased consumption of high-fat diets (HFDs). The influence of HFDs on intrinsic innervation and the intestinal wall has not been fully characterized. The aim of this study was to investigate the morpho-quantitative aspects of myenteric neurons and the wall of the small intestine in mice fed a HFD. METHODS: Swiss mice were fed a HFD (59% kcal from fat) or standard chow (9% Kcal from fat) for 8 weeks. Segments of the duodenum, jejunum, and ileum were subjected to histological processing for morpho-quantitative examination of the intestinal wall and mucosal cells, and immunohistochemistry was performed to evaluate myenteric neurons. The data for each segment were compared between the groups using an unpaired Student's t-test or an equivalent nonparametric test. RESULTS: The HFD increased body weight and visceral fat and decreased the length of the small intestine and the circumference of the ileum. In the duodenum, the HFD increased the density of the nitrergic subpopulation and decreased the area of nitrergic neurons and vasoactive intestinal peptide (VIP) varicosities. In the jejunum, the density of the nitrergic subpopulation was increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. In the ileum, the density of the general population and nitrergic subpopulation were increased and the neuronal areas of the general population, nitrergic subpopulation and (VIP) varicosities were reduced. The morphometric parameters of the villi, crypts, muscular layer and total wall generally increased in the duodenum and jejunum and decreased in the ileum. In the duodenum and jejunum, the HFD promoted a decreased in the proportion of intraepithelial lymphocytes. In the ileum, the proportion of intraepithelial lymphocytes and goblet cells reduced, and the enteroendocrine cells increased. CONCLUSIONS: The high-fat diet induces changes in the myenteric innervation of the small intestine, intestinal wall and mucosal cells responsible for the secretion of hormones and maintenance of the protective intestinal barrier. The morpho-quantitative data provide a basis for further studies to clarify the influence of HFD in the motility, digestive and absorptive capacity, and intestinal barrier.

High-fat diet promotes neuronal loss in the myenteric plexus of the large intestine in mice.

BACKGROUND: Obesity is considered a risk factor for other chronic diseases, and diets rich in lipids can cause alterations in the intestinal functions. AIM: The aim of this study was to investigate the effects of a high-fat diet (HFD) on the myenteric plexus of the large intestine in mice. METHODS: Swiss mice were distributed into four groups: Control animals fed standard chow for 8 and 17 weeks (C8 and C17 groups) and hyperlipidic animals fed HFD for 8 and 17 weeks (Ob8 and Ob17 groups). Immunofluorescence was performed in the large intestine for the morphologic and quantitative analysis of neuronal populations. RESULTS: Animals in the Ob17 group exhibited increased body weight and visceral fat gain compared with the C17 group. The intestinal area was also reduced in the two Ob groups. In the proximal colon, the Ob17 group exhibited 16.1 % reduction of the general neuronal density and 33 % reduction of the VIP-immunoreactive (IR) subpopulation. The general neuronal density in the distal colon was reduced by 45 % in the Ob17 group, and the nNOS-IR density was reduced by 35 %. The morphometry of neuronal cell bodies in the Ob17 group exhibited a reduction of the neuronal area of all of the neuronal populations studied in the proximal colon, with a reduction of the subpopulations of nNOS-IR and VIP-IR neurons in the distal colon. CONCLUSIONS: The HFD caused neuronal loss in the myenteric plexus, and nitrergic neurons were more resilient. The changes were more pronounced in the distal colon after 17 weeks.

Diabetic neuropathy: an evaluation of the use of quercetin in the cecum of rats.

AIM: To investigate the effect of quercetin supplementation on the myenteric neurons and glia in the cecum of diabetic rats. METHODS: Total preparations of the muscular tunic were prepared from the ceca of twenty-four rats divided into the following groups: control (C), control supplemented with quercetin (200 mg/kg quercetin body weight) (CQ), diabetic (D) and diabetic supplemented with quercetin (DQ). Immunohistochemical double staining technique was performed with HuC/D (general population)/nitric oxide synthase (nNOS), HuC-D/S-100 and VIP. Density analysis of the general neuronal population HuC/D-IR, the nNOS-IR (nitrergic subpopulation) and the enteric glial cells (S-100) was performed, and the morphometry and the reduction in varicosity population (VIP-IR) in these populations were analyzed. RESULTS: Diabetes promoted a significant reduction (25%) in the neuronal density of the HuC/D-IR (general population) and the nNOS-IR (nitrergic subpopulation) compared with the C group. Diabetes also significantly increased the areas of neurons, glial cells and VIP-IR varicosities. Supplementation with quercetin in the DQ group prevented neuronal loss in the general population and increased its area (P < 0.001) and the area of nitrergic subpopulation (P < 0.001), when compared to C group. Quercetin induced a VIP-IR and glial cells areas (P < 0.001) in DQ group when compared to C, CQ and D groups. CONCLUSION: In diabetes, quercetin exhibited a neuroprotective effect by maintaining the density of the general neuronal population but did not affect the density of the nNOS subpopulation.

Neuroprotective effect of quercetin on the duodenum enteric nervous system of streptozotocin-induced diabetic rats.

BACKGROUND: In diabetes mellitus (DM), hyperglycemia promotes changes in biochemical mechanisms that induce oxidative stress. Oxidative stress has been closely linked to adverse consequences that affect the function of the gastrointestinal tract caused by injuries to the enteric nervous system (ENS) that in turn cause neurodegeneration and enteric glial loss. Therapeutic approaches have shown that diet supplementation with antioxidants, such as quercetin, reduce oxidative stress. AIMS: This work sought to evaluate neurons and enteric glial cells in the myenteric and submucosal plexuses of the duodenum in diabetic rats supplemented with quercetin. METHODS: The duodenum of 24 rats, including a control group (C), control quercetin supplementation group (CQ), diabetic group (D), and diabetic quercetin supplementation group (DQ), were used to investigate whole mounts of muscular and submucosal layers subjected to immunohistochemistry to detect vasoactive intestinal peptide in the myenteric layer and double-staining for HuC-D/neuronal nitric oxide synthase (nNOS) and HuC-D/S100. RESULTS: A reduction of the general neuronal population (HuC/D) was found in the myenteric and submucosal plexuses (p < 0.001) in the D and DQ groups. The nitrergic subpopulation (nNOS) decreased only in the myenteric plexus (p < 0.001), and glial cells decreased in both plexuses (p < 0.001) in the D and DQ groups. In diabetic rats, quercetin supplementation reduced neuronal and glial loss. Diabetes promoted an increase in the cell body area of both the general and nitrergic populations. Quercetin supplementation only prevented neuronal hypertrophy in the general population. CONCLUSION: Supplementation with quercetin eased the damage caused by diabetes, promoting a neuroprotective effect and reducing enteric glial loss in the duodenum.

Neuroprotective action of Ginkgo biloba on the enteric nervous system of diabetic rats.

AIM: To investigate the effect of Ginkgo biloba extract on the enteric neurons in the small intestine of diabetic rats. METHODS: Fifteen Wistar rats were divided into three groups: control group (C), diabetic group (D) and diabetic-treated (DT) daily with EGb 761 extract (50 mg/kg body weight) for 120 d. The enteric neurons were identified by the myosin-V immunohistochemical technique. The neuronal density and the cell body area were also analyzed. RESULTS: There was a significant decrease in the neuronal population (myenteric plexus P = 0.0351; submucous plexus P = 0.0217) in both plexuses of the jejunum in group D when compared to group C. With regard to the ileum, there was a significant decrease (P = 0.0117) only in the myenteric plexus. The DT group showed preservation of the neuronal population in the jejunum submucous plexus and in the myenteric plexus in the ileum. The cell body area in group D increased significantly (P = 0.0001) in the myenteric plexus of both segments studied as well as in the ileum submucosal plexus, when compared to C. The treatment reduced (P = 0.0001) the cell body area of the submucosal neurons of both segments and the jejunum myenteric neurons. CONCLUSION: The purified Ginkgo biloba extract has a neuroprotective effect on the jejunum submucous plexus and the myenteric plexus of the ileum of diabetic rats.

Aspectos gerais e abordagem terapêutica da quercetina sobre as complicações do diabetes causadas pelo estresse oxidativo / General aspects and therapeutic of quercetin on the complications of diabetes caused by oxidative stress

Os flavonóides pertencem à classe de compostos fenólicos, que diferem entre si pela sua estrutura química e características particulares. Frutas, vegetais, grãos, flores, chá e vinho são exemplos de fontes destes compostos. A quercetina é o principal flavonóide presente na dieta humana, sendo a representante mais característica da subclasse flavonol da família dos flavonóides. Desde a sua descoberta, os estudos publicados na literatura científica apontam para o seu papel crucial no combate ao estresse oxidativo, associado a diversas condições patológicas. No diabetes mellitus (DM), por exemplo, também tem sido relatada sua eficiência na inibição da enzima aldose redutase que participa da via dos polióis. Nesta contextualização e considerando as graves consequências advindas do DM para a saúde e qualidade de vida, propôs-se neste trabalho uma revisão geral da literatura pertinente, a fim de reunir dados sobre aspectos biológicos e funcionais da quercetina, bem como, sua atuação benéfica nas complicações do diabetes causadas pelo estresse oxidativo.

Flavonoids belong to the class of phenolic compounds that differ by their chemical structure and characteristics. Fruits, vegetables, grains, flowers, tea and wine are examples of sources of these compounds. Quercetin is the major flavonoid present in the human diet and it is the most typical representative of the flavonol subclass of the flavonoid family. Since its discovery, studies published in scientific literature point to its crucial role in combating oxidative stress associated with various pathological conditions. In diabetes mellitus (DM), for example, it has been also reported the effectiveness in inhibiting aldose reductase enzyme that participates of polyol pathway. In this context and considering the dire consequences of diabetes to health and quality of life, it was proposed in this paper a general review of relevant literature in order to gather data on biological and functional aspects of quercetin and its beneficial role in the complications diabetes caused by oxidative stress.

Ginkgo biloba (EGb 761) extract: effects on the myenteric plexus of the large intestine in Wistar rats.

The objective of this study was to evaluate the effect of the purified extract of the Ginkgo biloba (EGb 761) plant on the myenteric plexus in the proximal and distal colon of Wistar rats for a period of 120 days. The experimental rats were divided into two age groups: a young group, sacrificed at age 90 days, and an adult group, sacrificed at age 210 days. We observed a significant reduction in the number of neurons in the myenteric plexus of the adult group compared to the young group in both of the segments studied (P < 0.01). The adult group treated with Ginkgo biloba showed a significant increase in neuronal profile area in both the segments studied (P < 0.001). It can be concluded from these results that treatment with the purified Ginkgo biloba (EGb 761) plant extract at a dose of 50 mg/kg body weight has neurotrophic effect on the myenteric plexus in the proximal and distal colon of rats after 120 days of treatment.