S‐allyl cysteine restores erectile function through inhibition of reactive oxygen species generation in diabetic rats

Abstract

SUMMARYExcessive production of reactive oxygen species (ROS) by an overactive nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system in penile tissue is an important mechanism of erectile dysfunction (ED). S-allyl cysteine (SAC), a bioactive component derived from garlic, was recently reported to exert versatile antioxidant properties. We hypothesized that SAC would be able to resolve diabetes-related ED by reducing ROS generation, and designed this study to investigate this possibility as well as to determine the related underlying mechanisms. A streptozotocin-induced diabetes rat model was established and used for comparative analysis of 4-week treatment regimens with insulin or SAC. The ratio of maximal intracavernous pressure (ICP) to mean arterial blood pressure (MAP) was measured to determine erectile function. Differential levels of ROS, NADPH oxidase subunits, nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling pathway, and apoptosis were evaluated in cavernous tissues. Max ICP/MAP was found to be markedly decreased in untreated diabetic rats; SAC, but not insulin, treatment restored the ratio to baseline (in non-diabetic untreated controls). The corpus cavernosum of untreated diabetic rats showed increased p47 phox and p67 phox expression, ROS production and penile apoptotic index, and decreased phospho-endothelial nitric oxide synthase (phospho-eNOS, Ser1177) expression, cGMP concentration, B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio and smooth muscle cell number. SAC treatment normalized all the diabetes-induced effects, whereas insulin treatment partially normalized the alterations, but produced no effects on P47 phox expression, penile ROS level, apoptotic index, Bcl-2/Bax ratio and smooth muscle cell number. Collectively, these data indicate that SAC treatment can restore erectile function in diabetic rats by preventing ROS formation through modulation of NADPH oxidase subunit expression. Furthermore, the poor efficacy of conventional insulin treatment for diabetic ED may be associated with an elevated level of ROS in penile tissue.

S‐allyl cysteine alleviates nonsteroidal anti‐inflammatory drug‐induced gastric mucosal damages by increasing cyclooxygenase‐2 inhibition, heme oxygenase‐1 induction, and histone deacetylation inhibition

“…Among these preparations, S-allyl cysteine (SAC), one of the major organic garlic compounds that had been known to possess a powerful anti-oxidant property, can be candidate for potential formula compared with other organosulfur compounds, including diallyl bisulfide, diallyl trisulfide (DAT3S), or diallyl-tetrasulfide (DAT4S). 9,10 Studies in mouse and rodent models have shown that SAC can be rapidly absorbed in the GI tract and has very low acute/subacute toxicity (LD50 value > 54.7 mM/kg oral; > 20 mM/kg intraperitoneal), which is 30-fold less toxic than other typical garlic compounds, such as allicin and diallyl disulfide. 11,12 Moreover, SAC is two hydrophilic cysteine-containing compounds naturally formed in garlic.…”

Reactive oxygen, nitrogen, and sulfur species in human male fertility. A crossroad of cellular signaling and pathology

“…However, in contrast to shown pathological effects of high concentrations of ˙NO, decreased bioavailability of ˙NO in reproductive system has negative impact on fertility too. Accordingly, it has been shown that vasculogenic erectile dysfunction is caused by decreased NOS activity and that decreased ˙NO bioavailability is common mechanism for erectile dysfunctions …”

Taurine Supplementation Improves Erectile Function in Rats with Streptozotocin-induced Type 1 Diabetes via Amelioration of Penile Fibrosis and Endothelial Dysfunction

“…21 The primary antibody was mouse antiea-SMA (1:150; Boster). Masson's trichrome staining was performed according to the standard protocol.…”