Is L-Glutathione More Effective Than L-Glutamine in Preventing Enteric Diabetic Neuropathy?

Diabetes and its complications appear to be multifactorial. Substances with antioxidant potential have been used to protect enteric neurons in experimental diabetes. This study evaluated the effects of supplementation with l-glutamine and l-glutathione on enteric neurons in the jejunum in diabetic rats. Rats at 90 days of age were distributed into six groups: normoglycemic, normoglycemic supplemented with 2 % l-glutamine, normoglycemic supplemented with 1 % l-glutathione, diabetic (D), diabetic supplemented with 2 % l-glutamine (DG), and diabetic supplemented with 1 % l-glutathione (DGT). After 120 days, the jejunums were immunohistochemically stained for HuC/D+ neuronal nitric oxide synthase (nNOS) and vasoactive intestinal polypeptide (VIP). Western blot was performed to evaluate nNOS and VIP. Submucosal and myenteric neurons were quantitatively and morphometrically analyzed. Diabetic neuropathy was observed in myenteric HuC/D, nNOS, and VIP neurons (p < 0.05). In the submucosal plexus, diabetes did not change nitrergic innervation but increased VIPergic neuronal density and body size (p < 0.05). Supplementation with l-glutathione prevented changes in HuC/D neurons in the enteric plexus (p < 0.05), showing that supplementation with l-glutathione was more effective than with l-glutamine. Myenteric nNOS neurons in the DGT group exhibited a reduced density (34.5 %) and reduced area (p < 0.05). Submucosal neurons did not exhibit changes. The increase in VIP-expressing neurons was prevented in the submucosal plexus in the DG and DGT groups (p < 0.05). Supplementation with l-glutathione exerted a better neuroprotective effect than l-glutamine and may prevent the development of enteric diabetic neuropathy.