Salivary exosomes as a new therapy to ameliorate diabetes mellitus and combat xerostomia and submandibular salivary glands dysfunction in diabetic rats.

Diabetes mellitus (DM) is one of the major metabolic diseases. Xerostomia and salivary gland dysfunction are of its common oral complications. Exosomes, as a new therapeutic potential containing nucleic acids, proteins and lipids, act as effective vehicles for target molecules delivery. Accordingly, their therapeutic use is gaining much interest. Therefore, this work aimed to assess the therapeutic efficacy of salivary exosomes in ameliorating DM and combating xerostomia as a complication of salivary gland dysfunction in diabetic rats. In the current study, salivary exosomes were injected intravenously to rats of group II (Salivary Exo-treated group) one week after diabetes induction. Group I (Diabetic group) was left untreated. Blood sugar level was checked weekly. Water intake, salivary flow rate, salivary amylase and serum nitric oxide were assessed before and after diabetes induction and at the end of the study. After 5 weeks from the beginning of the study, salivary gland tissues were dissected and examined histologically and ultrastructurally. Gene expression of the inflammatory markers NFkappaB/p65 and TNFalpha was assessed by polymerase chain reaction. The results showed that salivary exosomes reduced blood glucose levels and enhanced salivary glands' function. This was indicated by a decrease in water intake, salivary amylase and serum nitric oxide in addition to an increase in salivary flow rate. This was confirmed histologically, ultrastructurally and via downregulation of NFkappaB/p65 and TNFalpha gene expression. Our results concluded that salivary exosomes could be considered as a novel cell free based therapy in treatment of xerostomia and salivary gland dysfunction in DM.