Morphoquantitative Aspects of Nitrergic Myoenteric Neurons from the Stomach of Diabetic Rats Supplemented with Acetyl‐L‐Carnitine

Abstract

The NADPH-diaphorase (NADPH-d) positive myoenteric neurons from the body of the stomach of rats with streptozotocin-induced diabetes with or without supplementation with acetyl-L-carnitine (ALC) were evaluated. At the age of 105 days the animals were divided into four groups: normoglycaemic (C), normoglycaemic supplemented with ALC (CC), diabetic (D) and diabetic supplemented with ALC (DC). The supplementation with ALC (200 mg/kg body weight/day) to groups CC and DC was made during 105 days. After this period the animals were killed and the stomach removed and subjected to the histochemical technique of NADPH-d for the staining of the neurons of the myoenteric plexus. The area of 500 neurons of each group was investigated, as well as the neuronal density in an area of 23.84 mm(2) in each stomach. ALC promoted reduction (P < 0.05) of fasting glycaemia, water ingestion and areas of the profiles of the cell bodies of the NADPH-d neurons in the diabetic animals. The density of these neurons was not statistically different in the groups studied. It is suggested, therefore, a moderate neuroprotective effect of ALC, because the diminishment of the areas of the neuronal profiles in the supplemented diabetic animals, although being statistically significant relative to the non-supplemented diabetics, was not sufficient to equal the values from the non-diabetic controls.

Supplementation with 0.1% and 2% vitamin e in diabetic rats: analysis of myenteric neurons immunostained for myosin-V and nNOS in the jejunum

“…Similar results were found by Freitas et al (12) , who observed a significant 37.9% reduction in neuronal density in the jejunum in diabetic animals compared with non-diabetic animals. Other studies performed by our group have analyzed different segments of the gastrointestinal tract, including the ileum (3,22,46) , proximal colon (15,24,25,34,39) , and stomach (14) and showed similar results. This reduction in the number of myenteric neurons results from hyperglycemia, which initiates several biochemical events, such as disturbances in the polyol pathway, formation of AGEs, activation of the protein kinase C and hexosamine pathways, and glycolysis.…”

“…Similar results were found by Pereira et al (22) in the ileum of rats using the same experimental model. Other studies did not find significant results with regard to the number of nNOS-immunoreactive neurons in different segments of the gastrointestinal tract, such as stomach (14) , distal colon (44) , and duodenum (13) . According to Pereira et al (22) , this subpopulation of neurons is highly resistant to the action of free radicals produced by DM-induced hyperglycemia, explaining the results described above, including our study of enteric neurons.…”

“…Several studies have observed similar results in the ileum (22,26,46) and stomach (24) . According to Fregonesi et al (14) , increased NADPH utilization occurs in DM because of the activation of the aldose reductase and glutathione reductase pathways, thus reducing the availability of this metabolic cofactor for the NOS enzyme. Therefore, increased activity of the pathway responsible for NO synthesis in nitrergic neurons may occur in an attempt to increase NADPH, thus increasing cell volume.…”

Effects of ascorbic acid supplementation in ileum myenteric neurons of streptozotocin-induced diabetic rats

“…The STZ is a substance that induces the experimental diabetes and has been used to assess the behavior of neurons in the enteric nervous system of several gastrointestinal segments (Young et al 1992, Büttow et al 1997, Wrzos et al 1997, Zanoni et al 2003, Clebis et al 2004, Fregonesi et al 2005. In order to be effective in the diabetogenic activity it should be given in doses higher than 25mg/kg of body weight (Junod et al 1969).…”

“…Experimental period longer than 90 days cause less weight gain for diabetic animals (Zanoni et al 2003, Clebis et al 2004, Fregonesi et al 2005, Silverio et al 2008.…”