Effects of cancer-induced cachexia and administration of L-glutathione on the intestinal mucosa in rat.

Walker-256 tumor is an experimental model known to promote cachexia syndrome, oxidative stress, and systemic inflammation. This study evaluated the duodenal mucosa of rats with Walker-256 tumor administered with 1% L-glutathione, intending to evaluate the damage caused by cancer-associated cachexia in the gastrointestinal tract and the effects of antioxidant administration on mucosal protection. Twenty-four 55-day-old male Wistar rats were distributed into four groups: control (C); control administered with 1% L-glutathione (C-GSH); Walker-256 tumor (W) and Walker-256 tumor administered with 1% L-glutathione (W-GSH). After 14 days of treatment, the duodenum was harvested for morphometric analysis of the mucosa, proliferation, apoptosis, immunostaining of varicosities immunoreactive (IR) to vasoactive intestinal peptide (VIP) and 5-HT-IR cells, and quantification of mast cells and goblet cells. Walker-256 tumor-bearing rats showed cachexia syndrome, mucosal atrophy, reduced cell proliferation, reduced 5-HT-IR cells, and increased goblet cells and VIPergic varicosities, which were not reversed by L-glutathione. On the other hand, L-glutathione caused a reduction of cells in apoptosis and mast cell recruitment, demonstrating a partial recovery of the damage detected in the intestinal mucosa.

Protective effects of quercetin-loaded microcapsules on the enteric nervous system of diabetic rats.

Quercetin-loaded microcapsules (QLM) promote controlled release and higher bioavailability of quercetin, an antioxidant and neuroprotective agent. We evaluated the antioxidant effect of QLM on enteric innervation and in the oxidative status of the ileum of diabetic rats. Wistar adult rats (Rattus norvegicus) were used in six groups containing normoglycemic (N), diabetic (D) and either normoglycemic or diabetic groups treated with QLM at a dose of 10 mg/kg (NQ10 and DQ10, respectively) or 100 mg/kg (NQ100 and DQ100, respectively). DQ10 e DQ100 did not prevent overall neuronal loss in the total and cholinergic populations. Nitrergic population showed differences regarding the treatments: DQ10 preserved neurons in the nitrergic population whilst DQ100 increased nitrergic loss. Evaluation of the redox status showed pro-oxidant effects in NQ100 by t-butyl-induced chemiluminescence analysis. We observed a reduction in the carbonylic content and an increase of low molecular weight antioxidants for DQ10 e DQ100. Therefore, QLM treatment at a dose of 10 mg/kg acted positively on nitrergic neurons reducing oxidative damage induced by diabetes.

Anti- and pro-oxidant effects of quercetin stabilized by microencapsulation on interstitial cells of Cajal, nitrergic neurons and M2-like macrophages in the jejunum of diabetic rats.

Given the well-known antioxidant and neuroprotective properties of quercetin, the aim of this work was to evaluate the effects of quercetin stabilized by microencapsulation at two doses (10 mg kg-1 and 100 mg kg-1) on the oxidative/antioxidant status, number and morphological features of ICC, nitrergic neurons and M2-like macrophages in jejunum of diabetic rats. The rats were randomly distributed into six groups: normoglycemic control (N), diabetic control (D) and either normoglycemic or diabetic groups treated with quercetin-loaded microcapsules at a dose of 10 mg kg-1 (NQ10 and DQ10, respectively) or 100 mg kg-1 (NQ100 and DQ100, respectively). After 60 days, the jejunum was collected. Whole mounts were immunostained for Ano1, nNOS and CD206, and oxidative stress levels and total antioxidant capacity of the jejunum were measured. Diabetes led to a loss of ICC and nitrergic neurons, but increased numbers of M2-like macrophages and elevated levels of oxidative stress were seen in diabetic animals. High-dose administration of quercetin (100 mg kg-1) further aggravated the diabetic condition (DQ100) but this treatment resulted in harmful effects on healthy rats (NQ100), pointing to a pro-oxidant activity. However, low-dose administration of quercetin (10 mg kg-1) gave rise to antioxidant and protective effects on ICC, nNOS, macrophages and oxidative/antioxidant status in DQ100, but NQ100 displayed infrequent negative outcomes in normoglycemic animals. Microencapsulation of the quercetin may become promising alternatives to reduce diabetes-induced oxidative stress but antioxidant therapies should be careful used under healthy status to avoid toxic effects.

Rheumatoid arthritis induces enteric neurodegeneration and jejunal inflammation, and quercetin promotes neuroprotective and anti-inflammatory actions.

AIMS: The aim of our study was to study the pathological mechanisms induced by the rheumatoid arthritis (RA) on the Enteric Nervous System (ENS). MAIN METHODS: We evaluated the effect of the chronic arthritis and its treatment with 50 mg/kg quercetin alone (AQ) and combined with 17.5 mg/kg ibuprofen (AIQ) for 60 days on neurons, glial cells and intestinal wall. Other groups were used: control (C), arthritic (A) and arthritic treated with 17.5 mg/kg ibuprofen (AI). After 60 days, the jejunum was removed and processed for immunohistochemical techniques. Immunostainings were performed for HuC/D and S100 (myenteric and submucosal plexuses), and GFAP (only myenteric plexus), while immunolabeling for CD45 and CD20 lymphocytes was performed using cryosections. Western blot was performed for GDNF, S100 and GFAP. KEY FINDINGS: A group yielded a remarkable density decrease of the neurons and glial cells with morphometric changes in the myenteric and submucosal plexuses, reduction of the GDNF expression and GFAP-related parameters (GFAP expression, occupancy area and GFAP-expressing glial cells) and intestinal inflammation and atrophy of the mucosa and intestinal wall. AQ group substantially reversed most of these effects, except for intestinal atrophy of the jejunum. The AI and AIQ groups displayed lower beneficial results than AQ for parameters related to the neurons and glial cells, although AIQ did not prevent the inflammation of the mucosa. SIGNIFICANCE: The severe chronic rheumatoid arthritis induced severe effects on ENS and mucosa, and quercetin treatment continues to be an important antioxidant supplement preventing the progression of the RA severity.

In vitro antioxidant potential and in vivo effects of Schinus terebinthifolia Raddi leaf extract in diabetic rats and determination of chemical composition by HPLC-ESI-MS/MS.

The present study investigated the in vitro and in vivo antioxidant potential and phytochemical composition of Schinus terebinthifolia, which is widely used in folk medicine for various therapeutic purposes. The in vitro analyses indicated that the hydroethanolic extract (HE) had 312.50 ± 0.50 mg GAE/g of total phenols. It also presented anti-DPPH• and anti-ABTS•+ activity, reduced phosphomolybden and metal ions and blocked the bleaching of ß-carotene. The HE at concentrations of 3.0 and 2.0 µg/mL had TRAP values of 2.223 ± 0.018 and 1.894 ± 0.026 µM Trolox, respectively. The HE increased the availability of antioxidants in plasma in treated animals in vivo. HPLC-ESI-MS/MS indicated the presence of 11 phenols: cumaric acid, (+)-catechin, myricetin-3-O-glicuronide, kaempferol-3-O-glucoside, myricetin, myricitrin, quercetin, gallic acid, methyl galate, pentagalloyl glucose and ethyl galate. Thus, S. terebinthifolia has potential for the prevention or treatment of diseases that are related to oxidative stress, such as diabetes mellitus.

Antioxidant Effects of the Quercetin in the Jejunal Myenteric Innervation of Diabetic Rats.

PURPOSE: Enteric glial cells (EGCs) exert a critical role in the structural integrity, defense, and metabolic function of enteric neurons. Diabetes mellitus is a chronic disease characterized by metabolic disorders and chronic autonomic neuropathy. Quercetin supplementation, which is a potent antioxidant, has been used in order to reduce the effects of diabetes-induced oxidative stress. The purpose of this research was to investigate the effects of quercetin supplementation in the drinking water at a daily dose of 40 mg on the glial cells and neurons in the jejunum of diabetic rats. MATERIALS AND METHODS: Twenty 90-day-old male adult Wistar rats were split into four groups: normoglycemic control (C), normoglycemic control supplemented with quercetin (Q), diabetic (D), and diabetic supplemented with quercetin (DQ). After 120 days, the jejunums were collected, and immunohistochemical technique was performed to label S-100-immunoreactive glial cells and HuC/D-immunoreactive neurons. RESULTS: An intense neuronal and glial reduction was observed in the jejunum of diabetic rats. Quercetin displayed neuroprotective effects due to reduced cell body areas of neurons and glial cells in Q and DQ groups compared to their controls (C and D groups). Interestingly, quercetin prevented the glial and neuronal loss with a higher density for the HuC/D-immunoreactive neurons (23.06%) and for the S100-immunoreactive glial cells (14.55%) in DQ group compared to D group. CONCLUSION: Quercetin supplementation promoted neuroprotective effects through the reduction of neuronal and glial body areas and a slight prevention of neuronal and glial density reduction.

Restoration of density of interstitial cells of Cajal in the jejunum of diabetic rats after quercetin supplementation.

BACKGROUND: Interstitial cells of Cajal (ICC) are required for normal motility in the gastrointestinal tract. Depletion of ICC has been associated with diabetic gastroenteropathy. PURPOSE: To determine the effect of quercertin supplementation on anoctamin-1 (Ano1) immunoreactive ICC in the myenteric region (ICC-MY) and deep muscular plexus (ICC-DMP) in the jejunum of diabetic rats. METHODS: Thirty-two 90-day-old male Wistar rats were distributed into the following groups: normoglycemic (C), normoglycemic supplemented with quercetin (CQ; 40 mg daily), diabetic (D), and diabetic supplemented with quercetin (DQ; 40 mg daily). Diabetes was induced by streptozotocin injection. After 120 days, preparations of the jejunal muscular and submucosal layers were immunostained for Ano1 to visualize ICC. Evaluation of the immunofluorescence intensity as well as density of ICC was performed. RESULTS: The density of ICC-MY was 46% lower in group D compared to group C (p < 0.01); ICC-DMP were reduced by 37% (p > 0.05). After quercertin treatment, the densities of ICC-MY were significantly higher in the DQ group compared to group D (ICC-MY: 58%, p < 0.05). Supplementation with quercetin in normoglycemic animals (CQ) compared with group C did not significantly change the ICC density (p > 0.05). CONCLUSIONS: In STZ-treated diabetic rats, diabetes promoted a reduction in the density of jejunal ICC-MY with no significant effect on ICC-DMP. Supplementation with quercetin (DQ) appeared to protect ICC-MY from depletion in diabetes possibly due to its antioxidant action.