The effect of α-and δ-tocopherol-lipoic acid ester co-drugs on the response of the rabbit bladder to in vitro ischemia/reperfusion.

OBJECTIVE

Obstructive bladder dysfunction (OBD) caused by benign prostatic hyperplasia is a common medical problem in ageing men. As the prostate enlarges and compresses the urethra, the bladder wall thickness and the bladder is termed "compensated" because its function is still relatively normal. Subsequently, bladder function begins to fail and this change is termed "decompensation." The extent of decompensation progresses from mild through severe. Bladder decompensation is mediated by cyclical ischemia followed by reperfusion (I/R) resulting in an increased generation of free radicals and oxidative stress. Previous studies demonstrated that both vitamin E (tocopherol) and alpha-lipoic acid (LA) showed significant antioxidant activity in experimental urinary bladder oxidative stress models. We hypothesized that co-drugs derived from these antioxidants would result in enhanced antioxidant activity relative to either individual compound for the treatment of oxidative stress in the lower urinary tract.

MATERIAL AND METHODS

Two ester co-drugs of TOC and LA, tocopherol ester (α-TOCE) and δ-TOCE were synthesized. Six adult male New Zealand White (NZW) rabbits were divided into two groups of three rabbits each. Eight full thickness strips from each rabbit bladder were taken for in vitro I/R experiments. The strips from the first set were control rabbits (24 strips). Six strips were not incubated, while the remaining strips were incubated in α-TOCE dissolved in 1% (n=6) or 2.5% ethanol (n=6) solutions. These strips were not subjected to in vitro I/R. The strips from the second set were processed as follows: 6 strips were not incubated, while the remaining strips were incubated in α-TOCE dissolved in 1% (n=6) or in δ-TOCE dissolved in 2.5% ethanol. These strips were subjected to 1 hour in vitro ischemia followed by two hours reperfusion.

RESULTS

Preliminary studies demonstrated that neither antioxidant had any effect on the contractile responses to 1% or 2.5% ethanol. Neither antioxidant had any effect on the control contractile responses. Both antioxidants protected the tissue from the initial effects of ischemia. Both antioxidants had significant protective effects on the contractile responses to all forms of stimulation after the reperfusion period.

CONCLUSION

Incubation with both antioxidants had similar protective effects on responses both to ischemia and to reperfusion.