NAC Supplementation of Hyperglycemic Rats Prevents the Development of Insulin Resistance and Improves Antioxidant Status but Only Alleviates General and Salivary Gland Oxidative Stress.

Anna Zalewska,Agnieszka Kossakowska,Małgorzata Żendzian-Piotrowska,Mateusz Maciejczyk,Sara Zięba,Paula Kostecka-Sochoń,Jan Matczuk,Stefano Falone

doi:10.1155/2020/8831855

Anna Zalewska, Agnieszka Kossakowska + Show 6 more

Open Access

https://doi.org/10.1155/2020/8831855

Copy DOI

Abstract

Previous studies based on animal models demonstrated that N-acetylcysteine (NAC) prevents oxidative stress and improves salivary gland function when the NAC supplementation starts simultaneously with insulin resistance (IR) induction. This study is the first to evaluate the effect of a 4-week NAC supply on the antioxidant barrier and oxidative stress in Wistar rats after six weeks of high-fat diet (HFD) intake. Redox biomarkers were evaluated in the parotid (PG) and submandibular (SMG) salivary glands and stimulated whole saliva (SWS), as well as in the plasma and serum. We demonstrated that the activity of salivary peroxidase and superoxide dismutase and total antioxidant capacity were significantly higher in PG, SMG, and SWS of IR rats treated with NAC. It appears that in PG and SMG of rats fed an HFD, N-acetylcysteine supplementation abolishes oxidative modifications to proteins (evidenced by decreased content of advanced oxidation protein products (AOPP) and advanced glycation end products (AGE)). Simultaneously, it does not reverse oxidative modifications of lipids (as seen in increased concentration of 8-isoprostanes and 4-hydroxynonenal vs. the control), although it reduces the peroxidation of salivary lipids in relation to the group fed a high-fat diet alone. NAC administration increased protein levels in PG and SMG but did not affect saliva secretion, which was significantly lower compared to the controls. To sum up, the inclusion of NAC supplementation after six weeks of HFD feeding was effective in improving the general and salivary gland antioxidant status. Nevertheless, NAC did not eliminate salivary oxidative stress and only partially prevented salivary gland dysfunction.

Highlights

Insulin resistance (IR) is when the tissues are not sufficiently sensitive to insulin’s effects despite its normal or more often elevated blood levels
Insulin, and HOMA-IR levels in the high-fat diet (HFD) group were significantly higher compared to the controls (+39%, p ≤ 0:0001; +55%, p ≤ 0:0001; and +72%, p ≤ 0:0001, respectively) and the NAC-supplemented group (+27%, p ≤ 0:0001; +41%, p ≤ 0:0001; and +57%, p ≤ 0:0001, respectively)
total oxidant status (TOS) and Oxidative stress index (OSI) in the homogenate of the parotid salivary glands of HFD rats were significantly higher compared to the controls (+41%, p = 0:0003 and +70%, p ≤ 0:0001, respectively), while NAC supplementation decreased OSI in the parotid gland homogenate of HFD+NAC rats compared to the HFD group (-46%, p ≤ 0:0001, respectively)

Summary

Introduction

Insulin resistance (IR) is when the tissues are not sufficiently sensitive to insulin’s effects despite its normal or more often elevated blood levels. IR, together with obesity and severe systemic inflammation, play a vital role in the development of the so-called metabolic syndrome and cardiovascular diseases, psychiatric disorders, and cancers [1]. This applies especially to overweight and obese people who are at the highest risk of developing insulin resistance. It should be noted that OS is defined as the overproduction of oxygen and nitrogen free radicals exceeding the capacity of the antioxidant barrier responsible for their neutralization Due to this imbalance, an increase in oxidative modifications of proteins, lipids, DNA, and sugar compounds of the cell is observed, impairing the cells’ function and, the entire organs [7, 8]

Methods

Results

Conclusion