L-Glutamine Supplementation Prevents Myenteric Neuron Loss and Has Gliatrophic Effects in the Ileum of Diabetic Rats

Background Peripheral neuropathy caused chronically by diabetes mellitus is related to exacerbation of oxidative stress and a significant reduction in important endogenous antioxidants. l-Glutamine is an amino acid involved in defense mechanisms and is a substrate for the formation of glutathione, the major endogenous cellular antioxidant. Aim This study investigated the effects of 2% l-glutamine supplementation on peripheral diabetic neuropathy and enteric glia in the ileum in rats. Methods Male Wistar rats were divided into four groups: normoglycemics (N), normoglycemics supplemented with l-glutamine (NG), diabetics (D), and diabetics supplemented with l-glutamine (DG). After 120 days, the ileums were processed for HuC/D and S100 immunohistochemistry. Quantitative and morphometric analysis was performed. Results Diabetes significantly reduced the number of HuC/D-immunoreactive myenteric neurons per unit area and per ganglion in group D compared with normoglycemic animals (group N). l-Glutamine (2%) prevented neuronal death induced by diabetes (group DG) compared with group D. The glial density per unit area did not change with diabetes (group D) but was significantly reduced after l-glutamine supplementation (groups NG and DG). Ganglionic glial density was similar among the four groups. The neuronal area was not altered in groups D and DG. Glial size was reduced in group D; this was reversed by l-glutamine supplementation (group DG). Conclusions We concluded that 2% l-glutamine had neuroprotective effects directly on myenteric neurons and indirectly through glial cells, which had gliatrophic effects.