Mangiferin attenuates renal ischemia-reperfusion injury by inhibiting inflammation and inducing adenosine production

Abstract

Aim: Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, which is associated with high morbidity. The aims of the present study were to examine whether mangiferin attenuates renal IRI in an animal model and to identify the underlying mechanism(s).

Methods: Male mice were subjected to right renal ischemia for 30min followed by reperfusion for 24h or to a sham operation during which the left kidney was removed. After the 24h reperfusion, all mice were humanely euthanized and kidney tissues collected. Renal damage and apoptosis were investigated by examining hematoxylin and eosin-stained tissues, and by TUNEL assay and immunohistochemistry. Renal function was examined by measuring the concentrations of creatinine, blood urea nitrogen, and potassium (K(+)) in the serum. MPO activity, the levels of NO, TNF-α, IL-1β, and adenosine, and CD73 expression in renal tissue were also examined.

Results: Mangiferin reduced ischemia reperfusion-induced injury, improved kidney function, and inhibited both proinflammatory responses and tubular apoptosis. In addition, treatment with mangiferin increased adenosine production and CD73 expression in kidney's suffering IRI.

Conclusion: Mangiferin appears to attenuate renal IRI by inhibiting proinflammatory responses and tubular apoptosis and by increasing adenosine production. These effects are associated with the adenosine-CD73 signaling pathway.

Keywords: Adenosine; Inflammation; Ischemia reperfusion injury; Kidney; Mangiferin.