The blockade of muscarinic receptors in the management of overactive bladder (OAB) symptoms provides beneficial as well as adverse effects. The cognitive changes observed are caused by the drugs' ability to cross the blood-brain barrier and bind to muscarinic receptors within the central nervous system (CNS). To date, while not specifically testing for CNS side effects, most of the controlled efficacy trials of multiple OAB medications have not shown significant adverse effects on cognitive function. However, elderly individuals, in whom OAB is more prevalent, often are excluded from these studies. The few trials that have performed cognitive testing in healthy elderly people taking antimuscarinics have clearly shown that oxybutynin can adversely affect cognition. Darifenacin, trospium, solifenacin, and tolterodine appear to have little to no risk of causing CNS side effects in this population. However, caution needs to be used in elderly patients with preexisting dementia.

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The objective of this investigation was to analyze whether various combinations of the ROS scavengers glutathione (GSH), N-acetyl-cysteine (NAC), and vitamins C and E decrease DNA damage due to visible-light-irradiated (VL-irradiated) camphorquinone/N,N-dimethyl-p-toluidine (CQ/DMT) compared with individual vitamin C or E. PhiX-174 RF plasmid DNA was used to determine single and double strand breaks as parameters of DNA damage. Individual ROS scavengers and combinations of the antioxidants were added to plasmid DNA treated with VL-irradiated CQ/DMT/Cu (II). After incubation, DNA was loaded into a 1% agarose gel. Following electrophoresis, gels stained with 0.5 microg/mL ethidium bromide were photographed under ultraviolet illumination and analyzed with NIH ImageJ software. Results were evaluated between groups for statistical significance using Student's paired t-test (p < 0.05). Glutathione significantly reduced oxidative DNA damage at all test concentrations when combined with vitamin C or vitamin E. The concentration of damaged DNA observed in the presence of combinations of GSH with vitamin C or vitamin E was significantly lower compared with all other combinations of antioxidants investigated in our study (p < 0.05). In contrast to GSH, NAC was not able to compensate the pro-oxidative effects of vitamin C and vitamin E. Only at a concentration of 2 mM, NAC combined with vitamin C efficiently prevented CQ/DMT/Cu (II)-associated DNA damage. Our data indicate that solely the combinations of GSH with vitamin C or vitamin E significantly reduce the severity of oxidative DNA damage caused by CQ/DMT, whereas NAC may even increase the pro-oxidant activity of vitamin C and vitamin E.

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