Protective role of fenofibrate in sepsis-induced acute kidney injury in BALB/c mice

Abstract

Acute kidney injury (AKI) is a severe complication of sepsis, which largely contributes to the associated high mortality rate. Fenofibrate, a peroxisome proliferator activated receptor α (PPARα) agonist, has received considerable attention because of its effects related to renal damage-related energy metabolism and inflammation. The present study investigated the effects of fenofibrate on sepsis-associated AKI in BALB/c mice subjected to caecal ligation and puncture (CLP). Eight-week-old male BALB/c mice were divided into four groups: control group, fenofibrate group, caecal ligation and puncture (CLP) group, and fenofibrate + CLP group. CLP was performed after mice were gavaged with fenofibrate for 2 weeks. After 48 hours, we measured the histopathological alterations of the kidney tissue and plasma levels of serum creatinine (CRE), neutrophil gelatinase-associated lipocalin (NGAL), reactive oxygen species (ROS), ATP, and ADP. We evaluated PPARα and P53 protein levels as well as interleukin (IL)-1β, IL-6, and tumour necrosis factor-α mRNA levels. Our results showed that administering fenofibrate significantly reduced kidney histological alterations caused by CLP. Fenofibrate inhibited the plasma levels of ROS, CRE, NGAL, and increased the ATP/ADP ratio. Fenofibrate significantly inhibited elevations in P53, IL-1β, IL-6, and tumour necrosis factor-α expression. The results suggest that fenofibrate administration effectively modulates energy metabolism and may be a novel approach to treat sepsis-induced renal damage.