Differential effects of coenzyme Q10 and α-lipoic acid on two models of in vitro oxidative damage to the rabbit urinary bladder.
OBJECTIVE
Partial bladder outlet obstruction (PBOO) in rabbits causes free radical production through ischemia and reperfusion within the bladder smooth muscle and mucosa. We had previously shown that pretreatment of rabbits with a combination of α-lipoic acid (αLA) and coenzyme Q10 (CoQ) protected the bladder from contractile and metabolic dysfunctions mediated by PBOO. In this study, we examined the ability of pretreatment with αLA and CoQ combination in rabbits to protect the bladder from contractile damage mediated by either hydrogen peroxide (H(2)O(2)) or in vitro ischemia-reperfusion (I/R) which represents two in vitro models of oxidative damage.


METHODS
Eight adult male New Zealand white rabbits were pretreated with CoQ and αLA orally for four weeks. Eight adult male control rabbits were given vehicle. Eight full-thickness bladder strips were isolated from each of 4 treated and 4 control rabbit bladders, and a dose-response curve to H(2)O(2) (0.1-0.8%) was generated. Similarly, isolated strips of bladder from the remaining 4 control and 4 treated rabbits were subjected to 1 h of ischemia (no oxygen without glucose) followed by 2 h of incubation in oxygenated buffer with glucose. The effects on the contractile responses to field stimulation (FS) at 2, 8, and 32 Hz, carbachol, and potassium chloride (KCl) were determined.


RESULTS
H(2)O(2) reduced the contractile responses to KCl and carbachol to a significantly greater degree than to FS, whereas I/R reduced the contractile responses to FS to a significantly greater degree than to KCl and carbachol. Pretreatment of the rabbits with the combination of CoQ and αLA significantly protected the bladder from the damaging effects of I/R, but had virtually no effect on the damaging effects of H(2)O(2).


CONCLUSIONS
Although both H(2)O(2) and I/R are in vitro models of oxidative free radical damage to bladder smooth muscle, they have significantly different methods of action and different sensitivities to antioxidants.
Albany College of Pharmacy and Health Sciences, 106 New Scotland Ave, Albany, NY 12208, USA.
Hsin T
HT
Li
Catherine
C
Schuler
Robert E
RE
Leggett
Robert M
RM
Levin
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005500:Follow-Up Studies; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D018384:Oxidative Stress; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008063:Thioctic Acid / Q000627:therapeutic use*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001748:Urinary Bladder Neck Obstruction / Q000150:complications* / Q000503:physiopathology; D014815:Vitamins / Q000627:therapeutic use
D000975:Antioxidants; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014815:Vitamins; D014451:Ubiquinone; D008063:Thioctic Acid; C024989:coenzyme Q10