Effects of the Preservative Sodium Benzoate and a High-Fat Diet on Kidneys

Background: Sodium Benzoate (SB) is used as a food preservative and generally recognized as safe by the Food and Drug Administration (FDA). Reports suggest altered kidney function and oxidative stress in kidneys of mice exposed to SB. However, effects of dietary SB exposure on renal structures are unclear. Given the rising prevalence of obesity and increased risk of kidney disease with intake of ultraprocessed foods, effects of SB at dosages relevant to human dietary exposures coupled to a high fat diet, remain to be determined. This study addressed the hypothesis that SB with a high fat diet alters kidney histology and anti-oxidative mechanisms. Methods: 5-week-old male and female mice were assigned to either control diet (CD; 13% Kcal fat) or high fat diet (HFD; 42% Kcal fat). After 6 weeks, animals continued on their diet and assigned to groups gavaged with distilled water or distilled water containing SB (99mg/kg bw) daily for 28 days. Based on intake, this exposure approximated a highly processed diet where all food contained 0.1% added SB (FDA limit). Kidney sections were PAS-stained for histologic analysis of tubulo-interstitium and glomeruli. Protein abundance of superoxide dismutase (SOD-1), fibronectin, and glutamyl-cysteine synthetase (GCS) analyzed by western blot. Three-way ANOVA used to compare diet and SB effects between female and male. Two-way ANOVA used to compare diet and SB effects within either sex group. Results: Male mice had higher body weight than female mice in and all groups. Increased body weight from HFD was not altered by SB in male mice. Kidneys of mice in HFD, SB, and HFD+SB groups had focal areas of interstitial cell proliferation and fibrosis. Male mice on HFD had increased tubule vacuolization and a trend for increased glomerular mesangial matrix. Focal tubule injury/necrosis detected in kidneys of mice in HFD+SB groups. Abundance of SOD-1 was unaltered in all diet/treatments, while GCS was lower in kidneys of male mice. Conclusion: In conclusion, HFD and SB increased kidney tubule-interstitial fibrotic foci and tubule injury, suggesting that long term dietary intake of highly processed foods may cause kidney fibrosis, a hallmark of chronic kidney disease. Additionally, these findings suggest that HFD and SB may reduce protective measures against oxidative stress, a characteristic consistent with kidney disease. Funding: NIDDK Support