JAK1/JAK2 inhibitor baricitinib ameliorates sepsis-induced acute kidney injury in rats.

BACKGROUND

Baricitinib (Bar), used in the management of rheumatoid arthritis, is a selective inhibitor of JAK1/JAK2. Studies have shown that it inhibits the intracellular signaling of many proinflammatory cytokines by suppressing STAT3 activation. Increased expression and activity of JAK1/JAK2 and STAT3 are associated with kidney damage. Here, we examined the effects of the JAK1/JAK2 inhibitor baricitinib (Bar) on kidney damage in a sepsis model created with cecal ligation and puncture (CLP) in rats.

METHODS

Rats were divided into four groups: control, CLP, CLP + Bar 3 mg kg-1, and CLP + Bar 10 mg kg-1. The cecum of animals to which CLP was applied was first ligated distally, then punctured with a needle to allow the fecal content to spread into the abdominal cavity. Two different doses of Bar (3 mg kg-1, 10 mg kg-1) were applied to the treatment groups. Biochemical examinations were performed on the sera of animals sacrificed 24 h after CLP, while histopathological and immunohistochemical examinations were performed on kidney tissue.

RESULTS

Bar administration reduced the increased levels of BUN, Cr, TNF-α, IL-1β, KIM-1, NGAL and IL-18 in CLP-induced animal serum, and the levels of kidney tissue TLR-4, p-NF-κB, p-IκBα, IL-6, IL-1β, TNF-α, caspase-8, and caspase-3. At the same time, Bar application was observed to improve the damage in kidney tissue in histopathological examinations. These effects were more pronounced in the group administered 10 mg kg-1 Bar.

CONCLUSION

In this study, we found that Bar administration in the experimental sepsis model induced by CLP showed protective properties on the kidney by reducing inflammation and apoptosis dose-dependently.