Edaravone ameliorates experimental autoimmune thyroiditis in rats through HO-1-dependent STAT3/PI3K/Akt pathway

American Journal of Translational Research

Hong Li¹  Jie Min² 

[1] Department of Endocrinology, Long Hua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China;Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China

关键词: Edaravone;    experimental autoimmune thyroiditis;    HO-1;    STAT3;    PI3K/Akt;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Autoimmune thyroiditis is among the most prevalent of all the autoimmunities in population. It is characterized as both cellular immune responses with T, B cells infiltrating to the thyroid gland followed by hypothyroidism as a result of destruction of the thyroid follicles and fibrous replacement of the parenchymal tissue, as well as immune response for TPO and Tg-antibody production. Experimental autoimmune thyroiditis (EAT) has been proven to be an ideal model to study autoimmune thyroiditis. In the present study, we induced an EAT model in rats and examined the effect of edaravone, a hydroxyl radical scavenging agent, on EAT severity and explored the mechanism. The results showed that edaravone reduced the severity score of thyroiditis dose-dependently and the levels of serum TPOAb, TgAb, T3 and T4. Edaravone significantly decreased the mRNA level of IL-17, but increased the mRNA level of IL-10, IL-4, TNF-α and IFN-γ. EAT model significantly induced oxidative stress, which was inhibited by the treatment of 10 mg/kg, 20 mg/kg or 40 mg/kg of edaravone. The EAT model significantly increased the Akt and STAT3 phosphorylation, but when rats were treated with 20 mg/kg or 40 mg/kg edaravone, they were significantly inhibited. The HO-1 expression was greatly increased by 20 mg/kg or 40 mg/kg edaravone. The PI3K inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, Akt inhibitor triciribine or STAT3 inhibitor WP1066 all significantly decreased the severity score of thyroiditis in the EAT model group, while the HO-1 inhibitor ZnPP-IX increased the severity score of thyroiditis. These results confirm the invlovment of ROS and HO-1-dependent STAT3/PI3K/Akt pathway in the process of Hashimoto’s thyroiditis and suggest the potential usage of edaravone in the therapy of it.

【 授权许可】

CC BY-NC