Streptozotocin- induced changes of aquaporin 1 and 4, oxidative stress and autophagy in submandibular and parotid salivary glands and the possible ameliorative effect of intermittent fasting on these changes: immunohistochemical and molecular study in rats.

Salivary glands are greatly responsible for maintaining oral tissue homeostasis by the secretion of saliva. This study was designed to investigate the changes of aquaporin 1 and 4, oxidative stress and autophagy in submandibular and parotid salivary glands of diabetic rats and the possible ameliorative effect of intermittent fasting on these changes. Fifty adult male rats were divided into control and experimental groups. Experimental diabetes was induced by a single intraperitoneal injection of streptozotocin. After diabetic induction, the experimental group was divided into two groups (diabetic without intermittent fasting and diabetic with intermittent fasting). Animals were sacrificed two and four weeks after induction of diabetes. Intermittent fasting significantly decreased malondialdehyde and significantly elevated reduced glutathione (GSH) in the submandibular and parotid glands compared to those in diabetic rats. The salivary secretions were also significantly spared histologically in diabetics with intermittent fasting groups. As well, intermittent fasting up-regulated aquaporin 1 in both glands, while aquaporin 4 was only elevated in submandibular gland. Immunolocalization and gene expression of Lc3-II was higher in diabetic salivary glands than in fasting glands. In conclusion, these findings highlight the pathological role of autophagy in diabetic sub-mandibular and parotid glands and provide potential target for therapeutic role of intermittent fasting to ameliorate submandibular and parotid glands dysfunction in type I diabetes mellitus.