Food additive sodium carboxymethyl cellulose aggravates radiation-induced intestinal damage in mice by disrupting intestinal homeostasis

Abstract

Objective To explore the effect and underlying mechanism of long-term intake of sodium carboxymethyl cellulose (CMC-Na), a food additive, on radiation tolerance in mice. Methods Dietary intervention was performed on the mice by adding different concentrations of CMC-Na to drinking water at a dose of 0, 0.25% and 1%, respectively (Control and low-and high-dose groups) for 8 weeks, and then the mice were given a lethal radiation of 7 Gy 60Co gamma rays to establish a radiation damage model. Before and after the radiation intervention, the body weight was measured weekly in every mice, and death was observed and recorded in each group. After an 8-week intervention, the blood biochemical indicators of mice were assessed. ELISA, Qrt-Pcr, and Western blotting techniques to investigate changes in intestinal-related cytokines and proteins. What's more, HE staining, immunofluorescence assay and immunohistochemical staining were used to observe the changes of intestinal tissue morphology for pathological scores. Flow cytometry was employed to detect the proportion of intestinal stem cells. Results Flow cytometry showed that the proportion of intestinal stem cells was decreased in both dietary intervention groups when compared with the control group (P < 0.05), and the decrease was positively correlated with the dose of CMC-Na in drinking water and persisted after radiation damage. Higher death rate (P < 0.05) and obvious weight loss (P < 0.000 1) were observed in the high-dose intervention group, and impaired intestinal barrier function and a decrease in the content of the anti-inflammatory factor IL-10 were found in further research. Meanwhile, the expression levels of inflammatory factors such as TLR4, NF-κB, TNF-α and IL-1β were higher in the high-dose intervention group (P < 0.05), and the contents were further increased after radiation damage. The expression of certain inflammatory factors (NF-κB, TNF-α, and IL-1β) in the low-dose group exhibited a statistically significant increase compared to the control group (P < 0.05), yet remained lower than that observed in the high-dose group. Conclusion Long-term consumption of foods containing CMC-Na reduces the proportion of colonic stem cells in the intestinal tract, aggravates the radiation damage to the intestine, and reduces the radiation tolerance of mice.

Keywords

• sodium carboxymethylcellulose
• radiation
• intestinal barrier
• intestinal stem cells
• inflammation