Clinical significance of interleukin‑6 and inducible nitric oxide synthase in ketamine‑induced cystitis

Int J Mol Med. 2018 Feb;41(2):836-844. doi: 10.3892/ijmm.2017.3264. Epub 2017 Nov 17.

Abstract

Ketamine is an ionotropic glutamatergic N‑methyl‑D‑aspartate receptor antagonist, which is widely used among recreational drug abusers. Ketamine abusers exhibit substantially reduced bladder capacity, which can lead to urinary frequency. The molecular pathogenesis of ketamine‑induced cystitis has been scarcely reported. Given previous clinical findings, it may be hypothesized that pathological alterations in smooth muscle cells (SMCs) of the urinary bladder serve a crucial role in the mechanism underlying cystitis. In the present study, two lineages of SMCs, one from differentiated foreskin‑derived fibroblast‑like stromal cells and the other from cultured normal aortic SMCs, were used to study ketamine‑induced molecular alterations. Polymerase chain reaction was used to study the effects of ketamine on oxidative stress. The effects of adjuvant chemotherapy with cyclophosphamide (CTX) were also investigated. The results indicated that the expression levels of interleukin‑6 and inducible nitric oxide synthase (iNOS) were decreased, whereas collagen expression and deposition were increased in ketamine‑treated SMCs. Conversely, treatment with CTX restored the expression of iNOS, which may prevent or limit oxidative damage. In conclusion, the present study demonstrated that ketamine may induce several molecular alterations in SMCs and these changes may be associated with the clinical symptoms observed in ketamine abusers. In addition, the specific chemotherapeutic agent CTX may reverse these ketamine‑induced aberrations.

MeSH terms

  • Aorta / cytology
  • Aorta / drug effects
  • Cyclophosphamide / administration & dosage
  • Cystitis / chemically induced
  • Cystitis / drug therapy*
  • Cystitis / genetics
  • Cystitis / pathology
  • Gene Expression Regulation / drug effects
  • Humans
  • Interleukin-6 / genetics*
  • Ketamine / adverse effects*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / pathology
  • Nitric Oxide / genetics
  • Nitric Oxide Synthase Type II / genetics*
  • Oxidative Stress / drug effects
  • Urinary Bladder / drug effects
  • Urinary Bladder / pathology

Substances

  • Interleukin-6
  • Nitric Oxide
  • Ketamine
  • Cyclophosphamide
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II