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Toll 样受体和核因子 κB 信号通路参与某些食品防腐剂诱导大鼠肝肾氧化损伤。

Toll-like receptors and nuclear factor kappa B signaling pathway involvement in hepatorenal oxidative damage induced by some food preservatives in rats.

机构信息

Department of Forensic Medicine and Toxicology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.

Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, 44519, Egypt.

出版信息

Sci Rep. 2023 Apr 12;13(1):5938. doi: 10.1038/s41598-023-32887-9.

Abstract

Chemical food preservatives are extensively found in various processed food products in the human environment. Hence, this study aimed to investigate the effect of long-term exposure to five food preservatives (potassium sorbate (PS), butylated hydroxyanisole (BHA), sodium benzoate (SB), calcium propionate (CP), and boric acid (BA)) on the liver and kidney in rats and the probable underlying mechanisms. For 90 days, sixty male albino rats were orally given either water (control), 0.09 mg/kg b.wt BHA, 4.5 mg/kg b.wt PS, 0.9 mg/kg b.wt SB, 0.16 mg/kg b.wt BA, or 0.18 mg/kg b.wt CP. Liver and kidney function tests were assessed. Hepatic and renal oxidative stress biomarkers were estimated. Histologic examination analysis of liver and kidney tissues was achieved. Toll-like receptors 2 and 4 (TLR-2 and TLR-4), tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels were measured. The results revealed that long-term oral dosing of the five food preservatives resulted in significant increases in alkaline phosphatase, alanine transaminase, aspartate transaminase, urea, uric acid, and creatinine levels. There were significant reductions in hepatic and renal antioxidant enzymes, an increase in MDA concentrations, and pathological alterations in renal and hepatic tissues. The mRNA levels of TLR-4, TLR-2, NF-κB, and TNF-α were elevated in the food preservatives-exposed groups. Conclusively, the current findings revealed that long-term exposure to PS, BHA, SB, CP, and BA has a negative impact on liver and kidney function. Furthermore, these negative effects could be mediated via oxidative stress induction, inflammatory reactions, and cytokine production.

摘要

化学食品防腐剂广泛存在于人类环境中的各种加工食品中。因此,本研究旨在探讨长期暴露于五种食品防腐剂(山梨酸钾(PS)、丁基羟基茴香醚(BHA)、苯甲酸钠(SB)、丙酸钙(CP)和硼酸(BA))对大鼠肝脏和肾脏的影响及其可能的机制。在 90 天的时间里,给 60 只雄性白化大鼠口服水(对照)、0.09mg/kg bw BHA、4.5mg/kg bw PS、0.9mg/kg bw SB、0.16mg/kg bw BA 或 0.18mg/kg bw CP。评估了肝肾功能试验。估计了肝肾功能的氧化应激生物标志物。完成了肝肾功能组织学检查分析。测量了 Toll 样受体 2 和 4(TLR-2 和 TLR-4)、肿瘤坏死因子-α(TNF-α)和核因子 kappa-轻链增强子的 B 细胞(NF-κB)mRNA 表达水平。结果表明,五种食品防腐剂长期口服给药会导致碱性磷酸酶、丙氨酸转氨酶、天冬氨酸转氨酶、尿素、尿酸和肌酐水平显著升高。肝肾功能抗氧化酶显著降低,MDA 浓度升高,肾肝组织发生病理改变。TLR-4、TLR-2、NF-κB 和 TNF-α 的 mRNA 水平在暴露于食品防腐剂的组中升高。总之,目前的研究结果表明,长期暴露于 PS、BHA、SB、CP 和 BA 会对肝脏和肾脏功能产生负面影响。此外,这些负面影响可能是通过诱导氧化应激、炎症反应和细胞因子产生介导的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6d47/10097866/10731613a569/41598_2023_32887_Fig1_HTML.jpg

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