Protective effects of alpha-lipoic acid on memory deficit induced by repeated doses of solifenacin in mice: the role of nitro-oxidative stress.

Abstract

Solifenacin (Sol) is one of the most used antimuscarinics for the treatment of bladder dysfunction and there are no conclusive studies on its effects on learning and memory after long-term use. Since substances with antioxidant action, such as alpha-lipoic acid (ALA), have shown protective action in memory deficit and Alzheimer's disease, we decided to study the effects of Sol alone or associated with ALA in behavioral tests of memory and its relation to nitro-oxidative stress in different brain areas. Mice received saline or Sol p.o. for 14 or 28 days. ALA groups received: (a) saline + ALA, (b) Sol for 14 days and Sol + ALA from the 15th to the 28th days and, (c) Sol + ALA for 28 days. Behavioral tests were performed and oxidative changes (lipid peroxidation) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) were also determined. Sol produced memory alterations in the mice, reducing the step-down latency and the recognition index in the novel object recognition test. Sol also increased lipid peroxidation in PFC, HC and ST and nitrite levels in the HC. On the other hand, ALA associated with Sol was able to restrict the effects caused by Sol alone, both in relation to nitro-oxidative parameters and in relation to behavioral tests. Taken together, our data suggest that ALA can be administered as an adjunctive drug in patients requiring prolonged use of Sol to mitigate these adverse central nervous system effects. However, clinical studies need to be performed to corroborate preclinical research.