Akira Sato , Hina Nemoto , Tsukasa Matsumoto , Makoto Ohira
{"title":"酮体抑制肥大细胞降解并防止过敏反应","authors":"Akira Sato , Hina Nemoto , Tsukasa Matsumoto , Makoto Ohira","doi":"10.1016/j.phanu.2023.100359","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p><span>Ketone bodies<span> play critical roles in organismal energy homeostasis<span>; however, their effects on various diseases remain unknown. We investigated the effects of two ketone bodies, </span></span></span><em>β</em>-hydroxybutyric acid (<em>β</em><span>-HB) and acetoacetic acid (AcAc), on type I hypersensitivity </span><em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Methods</h3><p>The effects of <em>β</em>-HB and AcAc on mast cell degradation, as monitored by <em>β</em><span><span>-hexosaminidase release in rat basophilic leukemia RBL-2H3 cells, and hypothermic </span>anaphylaxis<span>, a potentially deadly allergic reaction, were evaluated in an anaphylactic mouse model.</span></span></p></div><div><h3>Results</h3><p>Both <em>β</em>-HB and AcAc inhibited <em>β</em>-hexosaminidase release from RBL-2H3 cells in a concentration-dependent manner. The inhibitory effects of AcAc were greater than those of <em>β</em>-HB. The inhibitory effects of <em>β</em><span>-HB and AcAc were significantly attenuated in the presence of a GPR109A receptor antagonist<span> mepenzolate bromide and GPR43A antagonist GLPG0974. </span></span><em>β</em><span>-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 </span><em>β</em>-HB (1–10 µmol/mouse) did not.</p></div><div><h3>Conclusions</h3><p>These results suggest that <em>β</em>-HB and AcAc, especially AcAc, are effective in type I hypersensitivity reactions, such as anaphylaxis, by inhibiting mast cell degradation.</p></div>","PeriodicalId":20049,"journal":{"name":"PharmaNutrition","volume":"26 ","pages":"Article 100359"},"PeriodicalIF":2.4000,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ketone bodies inhibit mast cell degradation and protect against anaphylaxis\",\"authors\":\"Akira Sato , Hina Nemoto , Tsukasa Matsumoto , Makoto Ohira\",\"doi\":\"10.1016/j.phanu.2023.100359\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p><span>Ketone bodies<span> play critical roles in organismal energy homeostasis<span>; however, their effects on various diseases remain unknown. We investigated the effects of two ketone bodies, </span></span></span><em>β</em>-hydroxybutyric acid (<em>β</em><span>-HB) and acetoacetic acid (AcAc), on type I hypersensitivity </span><em>in vitro</em> and <em>in vivo</em>.</p></div><div><h3>Methods</h3><p>The effects of <em>β</em>-HB and AcAc on mast cell degradation, as monitored by <em>β</em><span><span>-hexosaminidase release in rat basophilic leukemia RBL-2H3 cells, and hypothermic </span>anaphylaxis<span>, a potentially deadly allergic reaction, were evaluated in an anaphylactic mouse model.</span></span></p></div><div><h3>Results</h3><p>Both <em>β</em>-HB and AcAc inhibited <em>β</em>-hexosaminidase release from RBL-2H3 cells in a concentration-dependent manner. The inhibitory effects of AcAc were greater than those of <em>β</em>-HB. The inhibitory effects of <em>β</em><span>-HB and AcAc were significantly attenuated in the presence of a GPR109A receptor antagonist<span> mepenzolate bromide and GPR43A antagonist GLPG0974. </span></span><em>β</em><span>-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 </span><em>β</em>-HB (1–10 µmol/mouse) did not.</p></div><div><h3>Conclusions</h3><p>These results suggest that <em>β</em>-HB and AcAc, especially AcAc, are effective in type I hypersensitivity reactions, such as anaphylaxis, by inhibiting mast cell degradation.</p></div>\",\"PeriodicalId\":20049,\"journal\":{\"name\":\"PharmaNutrition\",\"volume\":\"26 \",\"pages\":\"Article 100359\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2023-09-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"PharmaNutrition\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2213434423000312\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"NUTRITION & DIETETICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"PharmaNutrition","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2213434423000312","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}
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.