Abstract

Oxidative stress plays a crucial role in the salivary gland dysfunction in insulin resistance; however, the cause of increased free radical formation in these conditions is still unknown. Therefore, the aim of the study was to investigate the effect of high-fat diet (HFD) on the mitochondrial respiratory system, prooxidant enzymes, ROS production, and nitrosative/oxidative stress in the submandibular and parotid glands of rats. The experiment was performed on male Wistar rats divided into two groups (n = 10): control and HFD. The 8-week feeding of HFD affects glucose metabolism observed as significant increase in plasma glucose and insulin as well as HOMA-IR as compared to the control rats. The activity of mitochondrial Complex I and Complex II+III was significantly decreased in the parotid and submandibular glands of HFD rats. Mitochondrial cytochrome c oxidase (COX) activity and the hydrogen peroxide level were significantly increased in the parotid and submandibular glands of the HFD group as compared to those of the controls. HFD rats also showed significantly lower reduced glutathione (GSH) and reduced : oxidized glutathione (GSH : GSSG) ratio, as well as a higher GSSG level in the parotid glands of HFD rats. The activity of NADPH oxidase, xanthine oxidase, and levels of oxidative/nitrosative stress (malonaldehyde, nitric oxide, nitrotyrosine, and peroxynitrite) and inflammation/apoptosis (interleukin-1β and caspase-3) biomarkers were statistically elevated in the HFD group in comparison to the controls. HFD impairs mitochondrial function in both types of salivary glands by enhancing ROS production, as well as stimulating inflammation and apoptosis. However, free radical production, protein nitration, and lipid peroxidation were more pronounced in the parotid glands of HFD rats.

Highlights

  • One of the most important problems of modern diabetology is a growing incidence of type 2 diabetes

  • General Characteristics. 8 weeks of feeding a high-fat diet caused significant increase in the body weight and body mass index (BMI) index of the rats from the study group compared to the control rats fed standard chow (p = 0 0003 and p = 0 0012, respectively)

  • The high-fat diet treatment affects glucose metabolism, as evidenced by the fact that we observed significant increase in blood glucose (p = 0 00001) and plasma insulin (p = 0 00001) concentrations as well as HOMA-insulin resistance (IR) (p = 0 0002) as compared to the control rats fed a regular diet

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Summary

Introduction

One of the most important problems of modern diabetology is a growing incidence of type 2 diabetes. Insulin resistance is an important element of the so-called metabolic syndrome, so it is considered an extremely serious health problem. The occurrence of insulin resistance is explained by the existence of insulin antibodies, accelerated insulin degradation, and/or insulin transmission disorders. In the pathogenesis of this phenomenon as well as its complications, the role of oxidative stress (OS) is emphasized [1]. Oxidative stress is a situation in which the temporarily or chronically elevated level of reactive oxygen species (ROS) cannot be neutralized by antioxidant systems, resulting in disturbances of cell metabolism and degradation of cellular components [2]

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