We have previously demonstrated that the farnesoid X receptor (FXR) agonist
obeticholic acid (OCA) protects the liver via downregulation of hepatic
matrix metalloproteinases (
MMPs) after
ischemia/reperfusion (I/R), which can lead to multiorgan dysfunction. The present study investigated the capacity of OCA to modulate
MMPs in distant organs such as the kidney. Male Wistar rats were dosed orally with 10 mg/kg/day of OCA (5 days) and were subjected to 60-min partial hepatic
ischemia. After 120-min reperfusion, kidney biopsies (cortex and medulla) and blood samples were collected. Serum
creatinine, kidney MMP-2, and MMP-9-dimer, tissue inhibitors of
MMPs (TIMP-1, TIMP-2), RECK,
TNF-alpha, and
IL-6 were monitored. MMP-9-dimer activity in the kidney cortex and medulla increased after hepatic I/R and a reduction was detected in OCA-treated I/R rats. Although not significantly, MMP-2 activity decreased in the cortex of OCA-treated I/R rats. TIMPs and RECK levels showed no significant differences among all groups considered. Serum
creatinine increased after I/R and a reduction was detected in OCA-treated I/R rats. The same trend occurred for tissue
TNF-alpha and
IL-6. Although the underlying mechanisms need further investigation, this is the first study showing, in the kidney, beneficial effects of OCA by reducing
TNF-alpha-mediated expression of
MMPs after liver I/R.