Ketamine induced renal fibrosis in a ketamine addition rat model

Abstract

ObjectiveThe toxicity of ketamine to the genitourinary system not only involves the lower urinary tract but also the upper urinary tracts. Reports showed that ketamine abuse may cause hydronephrosis and renal function deterioration. However, the exact pathophysiological mechanism of renal injury has not been investigated. The aim of the present study is to investigate the renal injury after ketamine addition in an animal model. Materials and methodsThirty Sprague–Dawley rats were divided into three groups: control group, K-14D group, and K-28D group. The K-14D and K-28D groups received ketamine (25 mg/kg/d, intraperitoneally) through daily injections for a period of 14 days and 28 days, respectively. Masson's trichrome stains were carried out to show the histological changes. Western blotting and reverse transcription polymerase chain reaction were carried out to examine the expressions of profibrosis markers and fibrosis-associated proteins. ResultsMasson's trichrome stain showed that no significant renal hydronephrosis occurred after ketamine treatment. However, ketamine treatment increased the fibrosis of the tubule-interstitium and increased collagen deposition and fibronectin expression. These alterations were accompanied by increases in the expression of inflammatory and fibrosis markers, fibronectin, and type I collagen after ketamine treatment. The profibrosis marker, transforming growth factor-β (TGF-β), increased significantly after 14 days and 28 days of ketamine treatment both in terms of mRNA and protein levels. ConclusionKetamine treatment not only induced cystitis-like syndrome, but also renal fibrosis. These renal interstitial fibrosis changes may be induced by the TGF-β pathway. These preliminary results can provide valuable information from a clinical perspective.