Effect of solifenacin plus and minus antioxidant supplements on the response to experimental outlet obstruction and overactive bladder dysfunction in rabbits—Part 2

Abstract

ObjectiveOne of the most common forms of bladder dysfunction is related to the development of unstable bladder contractions (bladder overactivity). Solifenacin is a relatively new, selective, antimuscarinic agent that has been shown to be particularly useful in the treatment of overactive bladder (OAB) dysfunctions in both men and women. Experimentally, we have demonstrated that OAB and obstructive bladder dysfunction are associated with the generation of free radicals and oxidative damage to the bladder. The hypothesis tested was that solifenacin + coenzyme Q10 + α-lipoic acid (CoQ + LA) would be more effective in the treatment of OAB than either would be individually. Materials and methodsForty-eight male White New Zealand rabbits were separated into 8 groups of 6 rabbits each. The following oral treatments were given to each group: Groups 1 and 5, vehicle (saline); Groups 2 and 6, solifenacin; Groups 3 and 7, CoQ + LA; Groups 4 and 8, solifenacin + CoQ + LA. After three weeks of treatment (by oral gavage), the rabbits in Groups 1–4 received partial outlet obstruction as detailed above. The rabbits continued their treatments for four weeks following surgery. At the end of this four-week period, immediately following urodynamic and physiological studies, the bladder was excised and the muscle and mucosa were separated and frozen for biochemical research. ResultsThe following marker enzymes were quantitated: choline acetyltransferase, citrate synthase, catalase, superoxide dismutase, and malondialdehyde (MDA, marker for lipid peroxidation). Solifenacin had no effect on citrate synthase activity of the bladder smooth muscle. However, pretreatment with both the antioxidants or the combination of solifenacin + antioxidants protected the citrate synthase activity such that it remained at control values. Partial outlet obstruction (PBOO) resulted in a 60% decrease in choline acetyltransferase activity (ChAT) activity, while solifenacin had no effect on reduced ChAT activity. Both the antioxidant and combination therapy resulted in maintaining ChAT activity at control values. PBOO resulted in a significant increase in MDA of both the muscle and mucosa. For both tissues, all treatments resulted in a significantly lower MDA content. In general, the results demonstrate the combination of solifenacin + antioxidants was more effective than either solifenacin or antioxidants alone. ConclusionThe addition of the antioxidants CoQ + LA works synergistically with solifenacin in the treatment of obstructive bladder dysfunction and OAB.