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Int J Radiat Oncol Biol Phys. 2018 Nov 17. pii: S0360-3016(18)34007-0. doi: 10.1016/j.ijrobp.2018.11.021. [Epub ahead of print]

Inorganic nitrate alleviates total body irradiation-induced systemic damage by decreasing reactive oxygen species levels.

Author information

1
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China.
2
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China; Departments of Biochemistry and Molecular Biology, Capital Medical University School of BasicMedical Sciences, Beijing, China.
3
Salivary Gland Disease Center and Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing, China; Departments of Biochemistry and Molecular Biology, Capital Medical University School of BasicMedical Sciences, Beijing, China. Electronic address: slwang@ccmu.edu.cn.

Abstract

PURPOSE/OBJECTIVE:

To evaluate the protective effect of inorganic nitrate against systemic damage in a mouse model of total body gamma irradiation (TBI).

METHODS/MATERIALS:

C57BL/6 mice in the IR (irradiation) + NaNO3 group were pretreated with 2 mmol/L NaNO3 in their drinking water for one week before receiving 5 Gy irradiation. Animals that received only 5 Gy irradiation were designated as the IR group. Survival and body weight were monitored. The peripheral blood lymphocytes (PBL), heart, liver, lung, and submandibular gland, were harvested and assessed. Reactive oxygen species (ROS) were measured in the lung and submandibular gland. Phosphorylated histone H2AX (p-H2AX) and p53-binding protein 1 (53BP1), as markers of early stage DNA damage, as well as terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Bax/Caspase 3 mRNA expression, as markers of apoptosis, were examined.

RESULTS:

No improvement of survival was observed in the IR + NaNO3 group after TBI, but the body weight loss after 5 Gy TBI was significantly attenuated in the IR + NaNO3 group. The levels of peripheral blood erythrocytes, leukocytes, and platelets at 7 days post-irradiation recovered with nitrate treatment; moreover, the p-H2AX level in the PBL was much lower in the IR + NaNO3 group at 2 h and 4 h post-irradiation. In the lung and submandibular gland, the levels of p-H2AX, 53BP1, and ROS as well as TUNEL staining were significantly decreased in the IR + NaNO3 group compared to those in the IR group. Gene expression of Bax and caspase 3 was decreased in both the lung and submandibular gland with nitrate treatment, indicating attenuation of apoptosis.

CONCLUSION:

Inorganic nitrate delivery could effectively prevent TBI-induced systemic damage. Nitrate-mediated decreases in ROS levels may contribute to this systemic protective effect.

KEYWORDS:

Apoptosis; DNA damage; Inorganic nitrate; Reactive oxygen species (ROS); Total body irradiation (TBI)

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