Allopurinol regulates abnormal kynurenine pathway metabolism and plays a role in treatment of adjuvant arthritis in rats
- Author:
Yue-Ye WANG
1
;
Cheng-Yan JIA
1
;
Yuan XU
1
;
He-Peng XU
1
;
A-Yuan CHEN
1
;
I Wei WE
1
;
Yan CHANG
1
Author Information
- Publication Type:Journal Article
- Keywords: adjuvant arthritis; allopurinol; kynurenine; rheumatoid arthritis; tryptophan; tryptophan 2,3- dlOXygenase
- From: Chinese Pharmacological Bulletin 2022;38(8):1176-1182
- CountryChina
- Language:Chinese
- Abstract: Aim To observe the therapeutie effeet of (AA) rats and its effect on the aetivity of tryptophan allopurinol ( ALLO) on adjuvant induced arthritis 2,3 dioxygenase (TDO).Methods SD rats were randomly divided into normal group, AA model group, ALLO group (10,20 , 40 mg • kg 1 ) and methotrexate group (0.5 mg • kg 1 ).The AA rats were established by intracutaneous injection of complete Freund's adju¬vant into the right toes of rats.The body weight,joint swelling number, joint pathology, spleen index and fi¬broblast like synoviocytes ( FLS) proliferation of the rats were observed to explore the therapeutic effect of ALLO.Flow cytometry detected the number of CD68 ∗ macrophages and the ratio of Thl7/Treg of spleen.The concentration of tryptophan ( Trp) and kvnurenine ( Kyn) in the liver and the supernatant of FLS were de¬termined by high performance liquid chromatography.Results Compared with model group, ALLO adminis¬ tration significantly increased the body weight of AA rats, reduced the number of joint swelling, improved joint pathological injury,decreased spleen index,inhib¬ited the proliferation of FLS, reduced the number of macrophages in the spleen,decreased Thl7/Treg ratio, inhibited the metabolism of Tip and the production of Kyn in liver and FLS culture supernatant, and de¬creased the liver Kyn/Trp ratio (TOO activity).Con¬clusion ALLO has therapeutic effect on AA rats, which may be related to its regulation of TDO-mediated kyn metabolism pathway.
