Pharmacokinetics and tissue distribution of orally administrated imidazole dipeptides in carnosine synthase gene knockout mice
Pharmacokinetics and tissue distribution of orally administrated imidazole dipeptides in carnosine synthase gene knockout mice
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口服咪唑二肽在肌肽合酶基因敲除小鼠体内的药代动力学及组织分布
DOI：
10.1093/bbb/zbac081
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Yanai Nobuya
中科院分区：
文献类型：
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作者：
Sakano Taiken;Egusa Ai Saiga;Kawauchi Yoko;Wu Jiawei;Nishimura Toshihide;Nakao Nobuhiro;Kuramoto Ayumu;Kawashima Takumi;Shiotani Shigenobu;Okada Yukio;Sato Kenichiro;Yanai Nobuya
咪唑二肽(ID)广泛存在于骨骼肌和脑中，具有抗氧化、缓冲pH、金属离子络合等多种功能。然而，ID的生理意义尚未完全阐明。在本研究中，我们对传统的肌肽合成酶基因缺陷小鼠(CANS-KO小鼠)口服ID以研究其药代动力学。分别以每公斤体重5 0 0 mg(∼2 mmoL)的剂量注射肌肽或安丝氨酸，测定组织中ID的含量。在未经治疗的Carns-KO小鼠中未检测到ID。在ID治疗组，ID给药后，腓肠肌、比目鱼肌和大脑组织中ID浓度呈时间依赖性增加。我们的发现表明，Carns-KO小鼠是一种有价值的动物模型，可以直接评估饮食ID的效果，并阐明口服ID的生理功能。
Imidazole dipeptides (ID) are abundant in skeletal muscle and the brain and have various functions, such as antioxidant, pH-buffering, metal-ion chelation. However, the physiological significance of ID has not been fully elucidated. In this study, we orally administered ID to conventional carnosine synthase gene-deficient mice (Carns-KO mice) to investigate the pharmacokinetics. Carnosine or anserine was administered at a dose of 500 mg (∼2 mmol) per kilogram of mouse body weight, and ID contents in the tissues were measured. No ID were detected in untreatedCarns-KO mice. In the ID treatment groups, the ID concentrations in the tissues increased in a time-dependent manner in the gastrocnemius muscle, soleus muscle, and cerebrum after ID administration. Our findings suggest that theCarns-KO mice are a valuable animal model for directly evaluating the effects of dietary ID and for elucidating the physiological functions of oral ID administration.