# Long‐Term Low‐Dose of Nitrate Administration Improves Antioxidant Defence System in Insulin‐Sensitive Tissues of Type 2 Diabetic Rats

## TL;DR

Long-term low-dose nitrate helps reduce oxidative stress in key tissues of diabetic rats, improving their antioxidant defenses.

## Contribution

This study shows that low-dose nitrate can protect insulin-sensitive tissues from oxidative stress in type 2 diabetes.

## Key findings

- Nitrate increased catalase and restored antioxidant capacity in the liver of diabetic rats.
- Nitrate reduced oxidative damage in muscle and adipose tissue of diabetic rats.
- Positive correlations were found between nitric oxide metabolites and antioxidant markers in multiple tissues.

## Abstract

Type 2 diabetes (T2D) is characterised by increased oxidative stress, which contributes to insulin resistance in insulin‐sensitive tissues. The objective of this study was to determine the antioxidative effects of long‐term nitrate administration in the liver, soleus muscle (SM) and epididymal adipose tissue (eAT) of male rats with T2D.

Rats were divided into four groups (n = 7): Control, Control+Nitrate (C + N), T2D and T2D + Nitrate (T2D + N). T2D was induced using a high‐fat diet followed by a low dose of streptozotocin (30 mg/kg). Nitrate (100 mg/L in drinking water) was administered for 6 months to the nitrate‐treated groups. Liver, SM and eAT were isolated, and tissue levels of catalase (CAT), total antioxidant capacity (TAC), reduced glutathione (GSH), malondialdehyde (MDA) and nitric oxide (NO) metabolites (NOx) were measured at the end of the study.

In the liver, nitrate increased CAT (216%, p < 0.001) and restored reduced TAC and GSH to normal values in rats with T2D. In the SM, nitrate decreased MDA (28%, p = 0.041) and restored reduced CAT to normal value in rats with T2D. In the eAT, nitrate increased CAT (72%, p = 0.046) and TAC (223%, p = 0.018) in rats with T2D. In addition, nitrate‐treated T2D rats had lower MDA (21.6%, p = 0.098) in the liver as well as higher TAC (104%, p = 0.064) in the SM and GSH (163%, p = 0.055) in the eAT; however, these changes were only marginally significant. Positive correlations were observed between NOx and CAT (p < 0.05 in SM and eAT), TAC (p < 0.05 in eAT) and GSH (p < 0.05 in liver, SM and eAT); furthermore, a marginally significant negative correlation was observed between NOx and MDA (p = 0.082 in liver and SM, p = 0.088 in eAT).

Long‐term nitrate administration at low doses has a protective effect against oxidative stress in the liver, SM and eAT of rats with T2D.

Long‐term nitrate administration at low doses has a protective effect against oxidative stress in the liver, soleus muscle (SM) and epididymal adipose tissue (eAT) of male rats with type 2 diabetes (T2D).