Evaluation of urinary bladder fibrogenesis in a mouse model of long-term ketamine injection

Mol Med Rep. 2016 Sep;14(3):1880-90. doi: 10.3892/mmr.2016.5482. Epub 2016 Jul 7.

Abstract

Long-term ketamine abuse has been shown to affect the lower urinary tract and result in interstitial cystitis-like syndrome. However, the causative mechanism of ketamine-induced dysfunction remains unclear. The present study aimed to investigate the physiological, histological and molecular changes on ketamine‑associated cystitis (KC) in a mouse model. Both male and female Balb/c mice were separately distributed into the control group (normal saline) and ketamine group, which received ketamine hydrochloride (100 mg/kg/day) daily by intraperitoneal injection for a total period of 20 weeks. In each group, the urine was analyzed by gas chromatography‑mass spectrometry to measure the concentration of ketamine and its metabolites. Urinary frequency and urine volume were examined to investigate the urinary voiding functions. Mice bladders were excised for cDNA microarray and hematoxylin and eosin (HE) staining. The ketamine and metabolites were detected only in ketamine‑treated mice urine. The voiding interval was reduced in the male mice group after 20 week ketamine administration. Additionally, the result of cDNA array analysis revealed a number of gene expression levels involved in chronic wound healing response and collagen accumulation, which were closely associated with fibrosis progression in the connective tissue. In HE staining of the bladder tissue, the ketamine-injected mice exhibited prominently denser blood vessel distribution in the submucosal layer. Based on the evidence in the present study, a mechanism that delineates fibrosis formation of urinary bladder induced by the pathogenesis of ketamine abuse can be constructed.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Female
  • Fibrosis / chemically induced*
  • Injections, Intraperitoneal
  • Ketamine / administration & dosage
  • Ketamine / metabolism
  • Ketamine / toxicity*
  • Ketamine / urine
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Urinary Bladder / drug effects*

Substances

  • Ketamine