INVESTIGATIVE UROLOGY

Dimethyl sulfoxide: does it change the functional properties of the bladder wall?
Melchior D, Packer CS, Johnson TC, Kaefer M
From the Departments of Urology, and Cellular and Integrative Physiology, Indiana University, Indianapolis, Indiana
J Urol. 2003; 170: 253-8

• Purpose: Dimethyl sulfoxide (DMSO) is used in a 50% solution to treat interstitial cystitis. Symptomatic relief occurs in about two-thirds of cases. The mechanism of action and effects of DMSO on bladder tissue function are poorly understood. Therefore, the effect of DMSO on bladder muscle compliance and contractility was evaluated.
• Materials and Methods: Contractility and compliance were evaluated in rat bladder strips exposed to various concentrations of DMSO for 7 minutes, followed by 7 to 60-minute washout periods. The effect of DMSO at concentrations of 25%, 30%, 35%, 40% and 50% on electrical field stimulation induced contractions was assessed. Acetylcholine and high KCl (Sigma Chemical Co.) induced contractions were measured after exposure to 30% DMSO. Compliance was evaluated after exposure to 30% and 50% DMSO.
• Results: Exposure to 40% DMSO completely abolished electrical field stimulation contractions, while 30% DMSO decreased the electrical field stimulation contraction to 40% ± 6% of the initial force but there was almost complete recovery within 30 minutes. Contractile force was unaltered by 25% DMSO. Acetylcholine and KCl stimulation after exposure to 30% DMSO produced contractile forces of 78% ± 6% and 39% ± 6% of pre-DMSO control contractions, respectively. Compliance decreased by 2.4 and 4.6-fold following 30% and 50% DMSO exposure, respectively.
• Conclusions: DMSO completely and irreversibly abolishes contractions at a 40% concentration. Compliance is altered at even lower concentrations (30%). These findings bring into question the current practice of treating patients who have IC with 50% DMSO. Lower concentrations (25%) of DMSO may serve as a safe, effective analgesic and anti-inflammatory treatment for IC and other bladder pathologies.
  
• Editorial Comment
  Interstitial cystitis (IC) has been described more 100 years ago; nevertheless, its pathogenesis and etiology remain unknown. For that reason, the treatments available for IC are empirical and symptomatic.
  Dimethyl sulfoxide (DMSO) is the treatment of choice for intravesical therapy in IC. DMSO is a scavenger of the intracellular OH radical believed to be an important trigger of inflammatory process (1). Although its mechanism of action in IC is not fully elucidated, this substance has multiple effects and DMSO treatment is associated with a low frequency of serious adverse effects. In general, DMSO is administered twice weekly as 50 ml sterile filtered 50% solution (2).
  The same group of the present work investigated previously the effect of DMSO on the proliferation of bladder smooth muscle cells in culture and noted that DMSO at high concentration (greater than 10%) can result in apoptotic cell death, while in low concentrations (less than 5%) it can act as an antiproliferative agent and inhibit cell growth in a dose dependent manner without direct cellular toxicity (3).
  In the present work, the authors demonstrated that application of DMSO at concentrations of 30% might lead to irreversible changes in bladder smooth muscle contractility and bladder tissue compliance. Although the current investigation has been performed in rats and in a nonphysiological environment (bladder strips), these results present cause for apprehension, because if these consequences also exist in vivo and in humans, the DMSO concentration of 50% may need to be reassessed for clinical use.

References
1. Peeker R, Fall M: The impact of heterogeneity on the diagnosis and treatment of interstitial cystitis. Int Braz J Urol. 2002; 28:10-9.
2. Childs SJ: Dimethyl sulfone (DMSO2) in the treatment of interstitial cystitis. Urol Clin North Am. 1994; 21: 85-8.
3. Kaefer M, Yerkes E, Rink RC: DMSO inhibits bladder smooth muscle cell proliferation. Presented at annual meeting of European Society of Pediatric Urology, Aarhus, Denmark, April 26-29, 2001.

Dr. Francisco J.B. Sampaio
Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil