Icilin, a cool/cold-inducing agent, alleviates lipopolysaccharide-induced septic sickness responses in mice
Copyright © 2023 Elsevier B.V. All rights reserved..
Sepsis is a significant global public health challenge, resulting in millions of human deaths annually. Transient receptor potential melastatin 8 (TRPM8), a non-selective ion channel, is the primary cold sensor in humans; however, its effects on endotoxin-induced inflammation remain unclear. We previously reported that TRPM8 knockout mice exhibited more severe physiological and behavioral endotoxemia responses upon a high-dose injection with lipopolysaccharide (LPS). In the present study, we investigated whether icilin, a TRPM8 agonist, was a target for the suppression of sickness responses using a mouse model of LPS-induced sepsis. A peripheral high-dose injection of LPS at 5 mg/kg showed a maximal body temperature decrease of 5.1 °C in mice subcutaneously pretreated with vehicle and 1.5 °C in icilin-pretreated animals. The decline in locomotor activity was attenuated in icilin-pretreated mice and its recovery was faster; however, the high-dose LPS injection rapidly decreased locomotor activity regardless of the icilin pretreatment. Furthermore, the icilin pretreatment attenuated LPS-induced decreases in body weight and food and water intakes and accelerated recovery from these sickness responses. Therefore, the present results demonstrated that the icilin pretreatment alleviated LPS-induced sickness responses or decreases in body temperature, locomotor activity, body weight loss, and food and water intakes, suggesting its potential as a therapeutic target for sepsis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:816 |
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| Enthalten in: |
Neuroscience letters - 816(2023) vom: 01. Nov., Seite 137492 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Komura, Mari [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.10.2023 Date Revised 21.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.neulet.2023.137492 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Sepsis is a significant global public health challenge, resulting in millions of human deaths annually. Transient receptor potential melastatin 8 (TRPM8), a non-selective ion channel, is the primary cold sensor in humans; however, its effects on endotoxin-induced inflammation remain unclear. We previously reported that TRPM8 knockout mice exhibited more severe physiological and behavioral endotoxemia responses upon a high-dose injection with lipopolysaccharide (LPS). In the present study, we investigated whether icilin, a TRPM8 agonist, was a target for the suppression of sickness responses using a mouse model of LPS-induced sepsis. A peripheral high-dose injection of LPS at 5 mg/kg showed a maximal body temperature decrease of 5.1 °C in mice subcutaneously pretreated with vehicle and 1.5 °C in icilin-pretreated animals. The decline in locomotor activity was attenuated in icilin-pretreated mice and its recovery was faster; however, the high-dose LPS injection rapidly decreased locomotor activity regardless of the icilin pretreatment. Furthermore, the icilin pretreatment attenuated LPS-induced decreases in body weight and food and water intakes and accelerated recovery from these sickness responses. Therefore, the present results demonstrated that the icilin pretreatment alleviated LPS-induced sickness responses or decreases in body temperature, locomotor activity, body weight loss, and food and water intakes, suggesting its potential as a therapeutic target for sepsis | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a Endotoxemia | |
| 650 | 4 | |a Hypothermia | |
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| 650 | 4 | |a LPS | |
| 650 | 4 | |a Lipopolysaccharide | |
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| 700 | 1 | |a Miyata, Seiji |e verfasserin |4 aut | |
| 700 | 1 | |a Yoshimura, Ryoichi |e verfasserin |4 aut | |
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