Quercetin increases bioavailability of nitric oxide in the jejunum of euglycemic and diabetic rats and induces neuronal plasticity in the myenteric plexus


      • Quercetin supplementation increased jejunal NO bioavailability in control and diabetic rats.
      • Diabetes decreased total and nitrergic neurons in the myenteric plexus of the jejunum.
      • Quercetin supplementation prevents diabetes-induced morphological changes.


      Considering the antioxidant, neuroprotective, inflammatory and nitric oxide modulatory actions of quercetin, the aim of this study was to test the effect of quercetin administration in drinking water (40 mg/day/rat) on neuronal nitric oxide synthase (nNOS), vasoactive intestinal peptide (VIP), overall population of myenteric neurons (HuC/D) and nitric oxide (NO) levels in the jejunal samples from diabetic rats. Male Wistar rats were distributed into four groups (8 rats per group): euglycemic (E), euglycemic administered with quercetin (E+Q), diabetic (D) and diabetic administered with quercetin (D+Q). Rats were induced to diabetes with streptozotocin (35mg/kg/iv) and, after 120 days, the proximal jejunum were collected and processed for immunohistochemical (VIP, nNOS and HuC/D) and chemiluminescence (quantification of tissue NO levels) techniques. Diabetes mellitus reduced the number of nNOS-IR (immunoreactive) (p <0.05) and HuC/D-IR (p <0.001) neurons, however, promoted an increased morphometric area of nNOS-IR neurons (p <0.001) and VIP-IR varicosities (p <0.05). In D+Q group, neuroplasticity effects were observed on HuC/D-IR neurons, accompanied by a reduction of cell body area of neurons nNOS- and VIP-IR varicosities (p <0.05). The NO levels were increased in the E+Q (p <0.05) and D+Q group (p <0.001) compared to the control group. In conclusion, the results showed that quercetin supplementation increased the bioavailability of NO in the jejunum in euglycemic and mitigate the effects of diabetes on nNOS-IR neurons and VIP-IR varicosities in the myenteric plexus of diabetic rats.

      Graphical abstract



      AUCs (areas under the curve), BSA (bovine serum albumin), D+Q (diabetic administered with quercetin), D (diabetic), DFO (deferoxamine), E+Q (euglycemic administered with quercetin), E (euglycemic), IR (immunoreactive), NO (Nitric oxide), PBS (phosphate-buffered saline), SBCAL (Brazilian Society of Science in Laboratory Animals), STZ (streptozotocin), VIP (Vasoactive Intestinal Peptide)
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