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, and CLP + Bar 10 mg kg. 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, 10 mg kg) 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 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.