Metformin alleviates inflammation in oxazolone induced ulcerative colitis in rats: plausible role of sphingosine kinase 1/sphingosine 1 phosphate signaling pathway

Abstract

Objectives

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is associated with high sphingosine kinase 1(SPHK1) expression in the colon, however its role in pathogenesis of UC is not clearly understood so, the aim of the present study was to clarify the role of SPHK1 and investigate whether the anti-inflammatory effects of metformin in UC is mediated by Sphingosine kinase 1/sphingosine 1 phosphate (S1P) signaling pathway.

Material and methods

Colitis was induced in adult male wistar rats by intra rectal administration of oxazolone in the fifth and seventh days from initial presensitization. Oxazolone treated rats were divided into untreated oxazolone group, metformin and mesalazine treated groups both in a dose of 100 mg/kg/day orally for 21 days. Along with these groups normal control and saline groups were used .Colitis was assessed by colon length, disease activity index (DAI) and histological examination of colontissue. Plasma samples were used to measure S1P.SPHK1 activity, signal transducer and activator of transcription −3(STAT-3), interleukin-6 (IL-6), nitric oxide (NO), myeloperoxidase activity (MPO), reduced glutathione (GSH) and tissue expression of intracellular cell adhesion molecule −1(ICAM-1) and caspase-3 genes were measured in tissue.

Results

Metformin successfully attenuated oxazolone colitis by increasing colon length, decreasing DAI and improved colon histologic picture. Metformin also induced a significant decrease in Plasma SIP, SPHK1 activity, inflammatory, oxidative stress markers, ICAM-1 and Caspase-3 genes expression compared to oxazolone group.

Conclusion

It is revealed that metformin alleviated inflammation and underlying mechanism may result from inhibition of SPHK1/S1P signaling pathway.

Keywords:

• Metformin
• ulcerative colitis
• sphingosine kinase
• sphingosine 1 phosphate
• IL-6

Acknowledgment

The authors wish to express special thanks to Prof Dr. Mohammed Ghanam, Faculty of veterinary medicine, Kafr EL-Sheikh University, for his assistance in histopathological investigations.

Disclosure statement

The authors declare that there are no conflicts of interest.