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J Therm Biol. 2017 Oct;69:163-170. doi: 10.1016/j.jtherbio.2017.07.007. Epub 2017 Jul 19.

L-Citrulline acts as potential hypothermic agent to afford thermotolerance in chicks.

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Graduate School of Bioresource and Bioenvironmental Science, Division for Experimental Natural Science, Faculty of Arts and Science, Kyushu University, Fukuoka 819-0395, Japan. Electronic address:
Laboratory of Regulation in Metabolism and Behavior, Graduate School of Bioresource and Bioenvironmental Science, Kyushu University, Fukuoka 812-8581, Japan.


Recently we demonstrated that L-citrulline (L-Cit) causes hypothermia in chicks. However, the question of how L-Cit mediates hypothermia remained elusive. Thus, the objective of this study was to examine some possible factors in the process of L-Cit-mediated hypothermia and to confirm whether L-Cit can also afford thermotolerance in young chicks. Chicks were subjected to oral administration of L-Cit along with intraperitoneal injection of a nitric oxide synthase (NOS) inhibitor, NG-nitro-l-arginine methyl ester HCl (L-NAME), to examine the involvement of NO in the process of hypothermia. Food intake and plasma metabolites were also analyzed after oral administration of L-Cit in chicks. To examine thermotolerance, chicks were orally administered with a single dose of L-Cit (15mmol/10ml/kg body weight) or the same dose twice within a short interval of 1h (dual oral administration) before the exposure to high ambient temperature (35 ± 1°C) for 180min. Although the rectal temperature was reduced following administration of L-Cit, L-NAME caused a greater reduction. L-NAME reduced total NO2 and NO3 (NOx) in plasma, which confirmed its inhibitory effect on NO. A single oral administration of L-Cit mediated a persistent state of hypothermia for the 300min of the study without affecting food intake. It was further found that plasma glucose was significantly lower in L-Cit-treated chicks. Dual oral administration of L-Cit, but not a single oral administration, afforded thermotolerance without a significant change in plasma NOx in chicks. In conclusion, our results suggest that L-Cit-mediated hypothermia and thermotolerance may not be involved in NO production. L-Cit-mediated thermotolerance further suggests that L-Cit may serve as an important nutritional supplement that could help in coping with summer heat.


Chicks; Hypothermia; L-Citrulline; Nitric oxide; Plasma glucose; Thermotolerance

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