Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

Ulcerative colitis (UC) is a chronic inflammatory disease characterized by diffused inflammation of the colon and rectum mucosa. The pathogenesis of UC is multifactorial, and the exact underlying mechanisms remain poorly understood. This study aims to investigate the effect of mesalazine and atorvastatin combination in enhancing anti‐inflammatory effects and attenuates progression of oxazolone colitis in rats. In the present study, male albino rats (N = 60) were divided into six groups (10 rats each), the first two groups served as normal control and a control saline group. Colitis was induced by intra‐rectal administration of oxazolone in the 5th and 7th days after pre‐sensitization. Then, rats were divided into untreated group, groups treated with mesalazine or atorvastatin or their combination. Colitis was assessed by colon length, body weight, and incidence of diarrhea, rectal bleeding, and histopathology of colon tissue. Colon tissues were used for measuring interleukin 6 (IL‐6), tumor necrosis factor alpha (TNF‐α), IL‐13, signal transducer and activator of transcription‐3 (STAT‐3), myeloperoxidase activity (MPO), reduced glutathione(GSH), and tissue expression of IL‐10, tight junction protein zonula occludens (ZO‐1), and caspase‐3 genes. The combination therapy significantly attenuated progression of UC by decreasing incidence of diarrhea, rectal bleeding, weight loss, IL‐13, IL‐6, TNF‐α, STAT‐3, caspase‐3, and MPO activity and significantly increased IL‐10, ZO‐1, colon length, and GSH content, and these effects were more superior to single drugs. These findings showed that combination therapy was able to ameliorate progression of UC and enhance anti‐inflammatory effects possibly by restoring IL‐10 and ZO‐1 levels and limiting IL‐6/STAT‐3 trans‐signaling.