Glycyrrhizic acid ameliorates submandibular gland oxidative stress, autophagy and vascular dysfunction in rat model of type 1 diabetes

Saad Mohamed Asseri,Nehal M Elsherbiny,Mohamed El-Sherbiny,Iman O Sherif,Alsamman M Alsamman,Nadia M Maysarah,Amira M Elsherbini

doi:10.1038/s41598-021-04594-w

Abstract

The burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). The present study aims to investigate the potential ameliorative effect of glycyrrhizic acid (GA) on diabetes-induced SMG damage. Experimental evaluation of GA treatment was conducted on a rat model of type I diabetes. Animals were assigned to three groups; control, diabetic and GA treated diabetic groups. After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. Also, parenchymal structures of the SMG were examined. GA alleviated the diabetes-induced SMG damage via restoring the SMG levels of oxidative stress markers and ET-1 almost near to the normal levels most probably via regulation of SIRT1, AQPs and accordingly LC-3, P62 and Beclin-1levels. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis.

Highlights

The burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG)
The present study reported for the first time the potential protective effect of glycyrrhizic acid (GA) on diabetes-induced SMG disorder
In agreement with our results, de Souza et al reported marked structural, functional, and biochemical alterations in salivary glands including SMG in STZ diabetic rats and theses alterations were reversed by ameliorating the hyperglycemic s tatus[21]

Summary

Introduction

The burden of diabetes mellitus (DM) and associated complications is increasing worldwide, affecting many organ functionalities including submandibular glands (SMG). After 8 weeks, the SMG was processed for assessment of oxidative stress markers, autophagy related proteins; LC3, Beclin-1 and P62, vascular regulator ET-1, aquaporins (AQPs 1.4 and 5), SIRT1 protein expressions in addition to LC3 and AQP5 mRNA expressions. GA could be a promising candidate for the treatment of diabetes-induced SMG damage via regulating oxidative stress, autophagy and angiogenesis. Subsequent diabetic complications that affect many organs and systems including oral tissue and salivary glands were reported[2]. Showed that diabetes was associated with characteristic histopathological alterations as well as decreased secretion of the SMG without affecting either the sublingual gland or parotid gland[3,5]. It is proposed that autophagy may play a crucial role in maintaining irradiated salivary glands[8,9]

Objectives

Results

Conclusion