title: Metabolic profiling provides a system understanding of hypothyroidism in rats and its application.
abstract: BACKGROUND
  Hypothyroidism is a chronic condition of endocrine disorder and its precise molecular mechanism remains obscure. In spite of certain efficacy of thyroid hormone replacement therapy in treating hypothyroidism, it often results in other side effects because of its over-replacement, so it is still urgent to discover new modes of treatment for hypothyroidism. Sini decoction (SND) is a well-known formula of traditional Chinese medicine (TCM) and is considered as efficient agents against hypothyroidism. However, its holistic effect assessment and mechanistic understanding are still lacking due to its complex components.
  
  
  RESULTS
  A urinary metabonomic method based on ultra performance liquid chromatography coupled to mass spectrometry was employed to explore global metabolic characters of hypothyroidism. Three typical hypothyroidism models (methimazole-, propylthiouracil- and thyroidectomy-induced hypothyroidism) were applied to elucidate the molecular mechanism of hypothyroidism. 17, 21, 19 potential biomarkers were identified with these three hypothyroidism models respectively, primarily involved in energy metabolism, amino acid metabolism, sphingolipid metabolism and purine metabolism. In order to avert the interference of drug interaction between the antithyroid drugs and SND, the thyroidectomy-induced hypothyroidism model was further used to systematically assess the therapeutic efficacy of SND on hypothyroidism. A time-dependent recovery tendency was observed in SND-treated group from the beginning of model to the end of treatment, suggesting that SND exerted a recovery effect on hypothyroidism in a time-dependent manner through partially regulating the perturbed metabolic pathways.
  
  
  CONCLUSIONS
  Our results showed that the metabonomic approach is instrumental to understand the pathophysiology of hypothyroidism and offers a valuable tool for systematically studying the therapeutic effects of SND on hypothyroidism.
authors: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors: Si
authors: S
authors: Wu
authors: Guangguo
authors: G
authors: Tan
authors: Xin
authors: X
authors: Dong
authors: Zhenyu
authors: Z
authors: Zhu
authors: Wuhong
authors: W
authors: Li
authors: Ziyang
authors: Z
authors: Lou
authors: Yifeng
authors: Y
authors: Chai
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D007037:Hypothyroidism / Q000378:metabolism* / Q000652:urine; D013058:Mass Spectrometry; D055432:Metabolomics; D015999:Multivariate Analysis; D051381:Rats; D013965:Thyroidectomy
chemical_list: D013956:Antithyroid Agents; D015415:Biomarkers