2-(4-morpholinoethyl)- 1-phenylcyclohexane-1-carboxylate hydrochloride (PRE-084) is a selective sigma 1 receptor agonist. It has been shown that
PRE-084 protected various tissues from experimental injury. However, no reports are available on its effect on renal
fibrosis. Rat model of
adenine-induced
chronic kidney disease was chosen to study this.
Adenine feeding in rats caused renal dysfunction as shown by increased serum
creatinine and reduced
creatinine clearance along with increased high molecular weight (HMW) urine
protein excretion. Further,
adenine feeding induced profibrotic changes in the kidney as reflected by increased expression of alpha-smooth muscle actin (α-SMA), fibroblast specific protein-1 (FSP-1) and
matrix metalloproteinase-2 (MMP-2) activity; reduced
cytokeratin expression. Further, there was excess deposition of extracellular matrix in the kidney, a striking character of
fibrosis. However, administration of
PRE-084 to
adenine fed rats led to reduction in
creatinine and
proteinuria parameters partly. This was accompanied by reduced expression of α-SMA, FSP-1 and MMP-2 activity and slight restoration of
cytokeratin levels leading to reduced extracellular matrix deposition in the kidney. These data demonstrate that
PRE-084 partly ameliorated renal dysfunction and exhibited anti-fibrotic potential in the kidney of
adenine fed rats.