Radioprotective Effect of Whey Hydrolysate Peptides against γ-Radiation-Induced Oxidative Stress in BALB/c Mice

Abstract

Radiation therapy is widely used in the treatment of tumor diseases, but it can also cause serious damage to the body, so it is necessary to find effective nutritional supplements. The main purpose of this study is to evaluate the protective effect of whey hydrolysate peptides (WHPs) against ⁶⁰Coγ radiation damage in mice and explore the mechanism. BALB/c mice were given WHPs by oral gavage administration for 14 days. Then, some mice underwent a 30-day survival test after 8 Gy radiation, and other mice received 3.5 Gy radiation to analyze the changes in body weight, hematology and bone marrow DNA after three and 14 days. In addition, through further analysis of the level of oxidative stress and intestinal barrier function, the possible mechanism of the radioprotective effect of WHPs was explored. The study found WHPs can prolong survival time, restore body weight, and increase the number of peripheral blood white blood cells and bone marrow DNA content in irradiated mice. In addition, WHPs can significantly improve the antioxidant capacity, inhibit pro-inflammatory cytokines and protect the intestinal barrier. These results indicate that WHPs have a certain radioprotective effect in mice, and the main mechanism is related to reducing oxidative damage.

Keywords: oxidative stress; radioprotective effect; whey hydrolysate peptides; γ-radiation-induced.

Figure 1

Study process diagram. IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 2

Kaplan–Meier survival curves of mice in each group. IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 3

General status of normal mice and irradiated mice.

Figure 4

Effect of WHPs on DNA content in bone marrow at day three after radiation. * The difference was statistically significant (p < 0.05) compared with the vehicle control group; # the difference was statistically significant (p < 0.05) compared with the IR control group. IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 5

Effect of WHPs on inflammatory cytokine levels in serum. * The difference was statistically significant (p < 0.05) compared with the vehicle control group; # the difference was statistically significant (p < 0.05) compared with the IR control group. IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 6

Effect of WHPs on intestinal morphology in irradiated mice (HE staining of sections, magnification: 200×). IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 7

Effect of WHPs on the expression of occludin proteins in mice (400×). IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.

Figure 8

Effect of WHPs on the expression of ZO-1 proteins in mice (400×). IR, irradiated mice; IR+WHPs-L, irradiated mice+low-dose whey hydrolysate peptides; IR+WHPs-M, irradiated mice+medium-dose whey hydrolysate peptides; IR+WHPs-H, irradiated mice+high-dose whey hydrolysate peptides.