The Novel Antioxidant, AC3056 (2,6-di-t-butyl-4-((Dimethyl-4-Methoxyphenylsilyl)Methyloxy)Phenol), Reverses Erectile Dysfunction in Diabetic Rats and Improves NO-mediated Responses in Penile Tissue from Diabetic Men

Q2 · MEDICINE

Article

Author: Iñigo Sáenz De Tejada ; Javier Angulo ; Concepción Peiró ; Rocío González-Corrochano ; Pedro Cuevas ; Sonia Gabancho ; José M. La Fuente ; Alain D. Baron ; Kim S. Chen ; Argentina Fernández

ABSTRACTIntroductionDiabetes is associated with a high incidence of erectile dysfunction (ED) and poor response to standard treatments. Oxidative stress could be relevant in the pathophysiology of diabetic ED.AimTo evaluate the effects of the antioxidant, AC3056 (2,6-di-t-butyl-4-((dimethyl-4-methoxyphenylsilyl)methyloxy)phenol), on diabetic ED.MethodsErectile responses to cavernosal nerve electrical stimulation were determined in streptozotocin-induced diabetic rats. Relaxation of human corpus cavernosal (HCC) tissue and penile resistance arteries (HPRA) from human cavernosal specimens was evaluated in organ chambers and myographs, respectively.Main Outcome MeasuresThe influence of AC3056 on erectile responses, lipid peroxidation, and nitrite plus nitrate serum content, and nuclear factor-κB (NF-κB) expression in penile tissue, in diabetic rats, and on endothelium-dependent and neurogenic relaxation of HCC and HPRA from diabetic patients was determined.ResultsEight weeks of diabetes caused ED in rats that was prevented by oral AC3056 (0.3% w/w in rat chow) when given from the induction of diabetes. AC3056 also prevented the diabetes-induced elevation of serum thiobarbituric acid-reactive substances (TBARS), the reduction of serum nitric oxide (NO) derivatives, and the increase of NF-κB expression. Acute oral administration of AC3056 (450 mg/kg) partially reversed ED in 8-week diabetic rats. Complete reversion of ED was achieved after 3 days of treatment with 0.3% AC3056. This effect remained after 5 weeks of treatment, but it disappeared after withdrawing for 1 week. Erectile function in diabetic rats was inversely related to serum TBARS. AC3056- (30 µM) reversed endothelial dysfunction in diabetic HCC and enhanced endothelium-dependent relaxation in diabetic HPRA and significantly potentiated neurogenic relaxation of both tissues. The reduced cGMP content in HCC from diabetic patients after exposure to acetylcholine (10 µM) was corrected by AC3056 (30 µM).ConclusionsThese results suggest that oxidative stress has a relevant role in pathophysiology of diabetic ED and provide a rationale for the use of antioxidant therapy in the treatment of ED in diabetes.

100 Deals associated with AC-3056

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KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05230

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Indication	Highest Phase	Country/Location	Organization	Date
Coronary Restenosis	Phase 2	US	-	-
Atherosclerosis	Phase 1	US	-	-
Atherosclerosis	Phase 1	-	Sanofi	-
Atherosclerosis	Phase 1	-	Bristol Myers Squibb Co. /Saint Nazaire Assets/	-
Coronary Restenosis	Phase 1	-	Sanofi	-
Coronary Restenosis	Phase 1	-	Bristol Myers Squibb Co. /Saint Nazaire Assets/	-
Vascular restenosis	Phase 1	US	-	-

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