Mast cells infiltration and decreased E-cadherin expression in ketamine-induced cystitis

Toxicol Rep. 2014 Dec 8;2:205-209. doi: 10.1016/j.toxrep.2014.12.003. eCollection 2015.


Background: Ketamine is a controlled substance and often illegally used as a recreational drug primarily by young adults. Increasing ketamine abusers associated with lower urinary tract symptoms have been reported at hospitals in recent years. Here we used a murine model to explore the changes of bladder in order to elucidate its pathogenesis.

Methods: ICR mice were randomly distributed into control and ketamine groups and received daily intraperitoneal injection of saline and ketamine (30 mg/kg), respectively. The bladders were excised and processed for histology at 4, 8 and 12 weeks. Tryptase and E-cadherin were investigated by immunohistochemistry in bladder tissues from ketamine-treated and control mice to assess the mast cell activation and junction protein expression.

Results: After ketamine treatment, the bladder changed to be hyperemic, inflamed, and with more fissures in mucosa. Compared with control group, the number of tryptase-positive mast cells significantly increased, which was 6.98 ± 2.89 and 23.00 ± 6.48 cells per field (100×) at 8 and 12 weeks, respectively (P = 0.016 and P = 0.003, respectively). Additionally, the expression of E-cadherin in ketamine-treated mice bladder tissue was significantly lower than that in the control tissues, P < 0.001.

Conclusions: Increased mast cells in bladder wall and downregulated expression of E-cadherin junction protein in epithelial cells were probably associated with interstitial inflammation and fissures in mucosa. It implied that ketamine induced an interstitial cystitis.

Keywords: Bladder; Cystitis; E-cadherin; Eosin (PubChem CID: 11048); Ethanol (PubChem CID: 702); Formaldehyde (PubChem CID: 712); Glutaradehyde (PubChem CID: 3485); Hematoxylin (PubChem CID: 442514); Ketamine; Ketamine (PubChem CID: 3821); Lead citrate (PubChem CID: 159739); Mice; Potassium ferrocyanide (PubChem CID: 11963580); Uranyl acetate (PubChem CID: 10915); Xylene (PubChem CID: 7237).