酮体抑制肥大细胞降解并防止过敏反应

IF 2.4 Q3 NUTRITION & DIETETICS PharmaNutrition Pub Date : 2023-09-27 DOI:10.1016/j.phanu.2023.100359
Akira Sato , Hina Nemoto , Tsukasa Matsumoto , Makoto Ohira
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引用次数: 0

摘要

酮体在机体能量稳态中起着关键作用;然而,它们对各种疾病的影响仍然未知。我们在体外和体内研究了两种酮体,β-羟基丁酸(β-HB)和乙酰乙酸(AcAc)对I型超敏反应的影响。方法通过大鼠嗜碱性白血病RBL-2H3细胞释放β-己糖胺酶来监测β-HB和AcAc对肥大细胞降解的影响,并在过敏小鼠模型中评估低温过敏反应(一种潜在的致命过敏反应)。结果β-HB和AcAc均以浓度依赖性方式抑制RBL-2H3细胞释放β-己糖苷酶。AcAc的抑制作用大于β-HB。在GPR109A受体拮抗剂溴化甲苯甲酸酯和GPR43A拮抗剂GLPG0974的存在下,β-HB和AcAc的抑制作用显著减弱。β-HB和AcAc在低于100µmol/L的浓度下不影响RBL-2H3细胞的活力。在过敏性小鼠模型中,腹腔注射AcAc(1µmol/小鼠)抑制过敏性体温过低,而注射β-HB(1-10µmol/鼠)则没有。结论β-HB和AcAc,尤其是AcAc通过抑制肥大细胞降解,对过敏反应等I型超敏反应有效。
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Ketone bodies inhibit mast cell degradation and protect against anaphylaxis

Background

Ketone bodies play critical roles in organismal energy homeostasis; however, their effects on various diseases remain unknown. We investigated the effects of two ketone bodies, β-hydroxybutyric acid (β-HB) and acetoacetic acid (AcAc), on type I hypersensitivity in vitro and in vivo.

Methods

The effects of β-HB and AcAc on mast cell degradation, as monitored by β-hexosaminidase release in rat basophilic leukemia RBL-2H3 cells, and hypothermic anaphylaxis, a potentially deadly allergic reaction, were evaluated in an anaphylactic mouse model.

Results

Both β-HB and AcAc inhibited β-hexosaminidase release from RBL-2H3 cells in a concentration-dependent manner. The inhibitory effects of AcAc were greater than those of β-HB. The inhibitory effects of β-HB and AcAc were significantly attenuated in the presence of a GPR109A receptor antagonist mepenzolate bromide and GPR43A antagonist GLPG0974. β-HB and AcAc did not affect the viability of RBL-2H3 cells at concentrations below 100 µmol/L. In an anaphylactic mouse model, the intraperitoneal injection of AcAc (1 µmol/mouse) inhibited anaphylactic hypothermia, whereas the injection of β-HB (1–10 µmol/mouse) did not.

Conclusions

These results suggest that β-HB and AcAc, especially AcAc, are effective in type I hypersensitivity reactions, such as anaphylaxis, by inhibiting mast cell degradation.

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来源期刊
PharmaNutrition
PharmaNutrition Agricultural and Biological Sciences-Food Science
CiteScore
5.70
自引率
3.10%
发文量
33
审稿时长
12 days
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