Analysis of the protective effects of γ-aminobutyric acid during fluoride-induced hypothyroidism in male Kunming mice

摘要

Context: Compounds to treat hypothyroidism in the absence of cardiac side effects are urgently required.In this regard, c-aminobutyric acid (GABA) has gained interest due to its anti-anxiolytic, antihypertensiveand antioxidant properties, and reported benefits to the thyroid system.Objective: We investigated the ability of GABA to ameliorate fluoride-induced thyroid injury in mice, andinvestigated 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 daysas a model of hypothyroidism. To evaluate the effects of GABA administration, fluoride-exposed micereceived either thyroid tablets, or low (25 mg/kg), medium (50 mg/kg) or high (75 mg/kg) concentrationsof 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. Effectson thyroid hormone production, oxidative stress, thyroid function-associated genes, and side-effects duringtherapy were measured.Results: GABA supplementation in fluoride-exposed mice significantly increased the expression of thyroidTG, TPO, and NIS (P 0.05), significantly improved the thyroid redox state (P 0.05), modulated theexpression of thyroid function-associated genes, conferred liver metabolic protection, and preventedchanges to myocardial morphology, thus reducing side effects. Both pure and laboratory-separated GABAdisplayed comparative protective effects.Discussion and conclusion: Our findings support the assertion that GABA exerts therapeutic potential inhypothyroidism. The design and use of human GABA trials to improve therapeutic outcomes in hypothyroidismare now warranted.