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Pharmaceutical Biology Volume 57 ,Issue 1 ,2019-01-01
Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice
Research Article
Haoyue Yang 1 , 2 , 3 Ronge Xing 1 , 2 , 3 Song Liu 1 , 2 , 3 Huahua Yu 1 , 2 , 3 Pengcheng Li 1 , 2 , 3
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DOI:10.1080/13880209.2018.1563621
Received 2018-5-14, accepted for publication 2018-12-12, Published 2018-12-12
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摘要

Context: Compounds to treat hypothyroidism in the absence of cardiac side effects are urgently required. In this regard, γ-aminobutyric acid (GABA) has gained interest due to its anti-anxiolytic, antihypertensive and antioxidant properties, and reported benefits to the thyroid system.Objective: We investigated the ability of GABA to ameliorate fluoride-induced thyroid injury in mice, and investigated the mechanism(s) associated with GABA-induced protection.Materials and methods: Adult male Kumning mice (N = 90) were exposed to NaF (50 mg/kg) for 30 days as a model of hypothyroidism. To evaluate the effects of GABA administration, fluoride-exposed mice received either thyroid tablets, or low (25 mg/kg), medium (50 mg/kg) or high (75 mg/kg) concentrations of pure GABA orally for 14 days groups (N = 10 each). The effects of low (50 mg/kg); medium (75 mg/kg) and high (100 mg/kg) concentrations of laboratory-separated GABA were assessed for comparison. Effects on thyroid hormone production, oxidative stress, thyroid function-associated genes, and side-effects during therapy were measured.Results: GABA supplementation in fluoride-exposed mice significantly increased the expression of thyroid TG, TPO, and NIS (P < 0.05), significantly improved the thyroid redox state (P < 0.05), modulated the expression of thyroid function-associated genes, conferred liver metabolic protection, and prevented changes to myocardial morphology, thus reducing side effects. Both pure and laboratory-separated GABA displayed comparative protective effects.Discussion and conclusion: Our findings support the assertion that GABA exerts therapeutic potential in hypothyroidism. The design and use of human GABA trials to improve therapeutic outcomes in hypothyroidism are now warranted.

关键词

anti-hypothyroidism;myocardial preservation;thyroid hormone synthesis;GABA

授权许可

© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Effects of γ-aminobutyric acid (GABA) on thyroglobulin (TG), sodium/iodide symporter (NIS) and thyroid peroxidase (TPO) in hypothyroidic mice. ‘a’ represents the groups with the largest mean values. The mean values decreased from ‘a’ to ‘e’. Groups marked with different letters are statistically different (P ≤ 0.05). NCG: mice administered only pure water for 14 days; PCG: mice administered thyroid tablets at a daily dose of 50 mg/kg for 14 days; G1: mice administered pure GABA at a daily dose of 50 mg/kg for 14 days; G2: mice administered pure GABA at a daily dose of 75 mg/kg for 14 days; G3: mice administered pure GABA at a daily dose of 100 mg/kg for 14 days; LSG1: mice administered laboratory-separated GABA at a daily dose of 50 mg/kg for 14 days; LSG2: mice administered laboratory-separated GABA at a daily dose of 75 mg/kg for 14 days; LSG3: mice administered laboratory-separated GABA at a daily dose of 100 mg/kg for 14 days.

Changes in malondialdehyde (MDA), glutathione reductase (GR) and ascorbate peroxidase (APX) levels after fluoride treatment with or without GABA and liver-protecting tablet administration. Analysis of variance between multiple groups was performed using the least significant difference method. ‘*’ indicates significance at the 0.05 level. ‘**’ indicates significance at the 0.01 level. NCG: mice administered only pure water for 14 days; PCG: mice administered thyroid tablets at a daily dose of 50 mg/kg for 14 days; G1: mice administered pure GABA at a daily dose of 50 mg/kg for 14 days; G2: mice administered pure GABA at a daily dose of 75 mg/kg for 14 days; G3: mice administered pure GABA at a daily dose of 100 mg/kg for 14 days; LSG1: mice administered laboratory-separated GABA at a daily dose of 50 mg/kg for 14 days; LSG2: mice administered laboratory-separated GABA at a daily dose of 75 mg/kg for 14 days; LSG3: mice administered laboratory-separated GABA at a daily dose of 100 mg/kg for 14 days.

Effects of GABA on the myocardial microstructure of hypothyroidic mice. Arrows marked by the letter ‘A’ depict swelling of the nucleus. Arrows marked by the letter ‘B’ depict karyopyknosis. CG: control group; NCG: mice administered only pure water for 14 days; PCG: mice administered thyroid tablets at a daily dose of 50 mg/kg for 14 days; G1: mice administered pure GABA at a daily dose of 50 mg/kg for 14 days; G2: mice administered pure GABA at a daily dose of 75 mg/kg for 14 days; G3: mice administered pure GABA at a daily dose of 100 mg/kg for 14 days; LSG1: mice administered laboratory-separated GABA at a daily dose of 50 mg/kg for 14 days; LSG2: mice administered laboratory-separated GABA at a daily dose of 75 mg/kg for 14 days; LSG3: mice administered laboratory-separated GABA at a daily dose of 100 mg/kg for 14 days.

通讯作者

Ronge Xing.Key Laborotory Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China;Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory for Marine Science and Technology, Qingdao, China;Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao, Chin.xingronge@qdio.ac.cn

推荐引用方式

Haoyue Yang,Ronge Xing,Song Liu,Huahua Yu,Pengcheng Li. Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice. Pharmaceutical Biology ,Vol.57, Issue 1(2019)

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