Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia

Abstract

Hyperlipidemia is considered one of the most important risk factors for erectile dysfunction (ED). To determine the effect of sodium tanshinone IIA sulfonate (STS) as an antioxidant agent on ED in high-fat diet- (HFD-) induced hyperlipidemia in rats and to investigate if STS administration could improve erectile function via hydrogen sulfide (H2S) production by inhibition of oxidative stress. Hyperlipidemia was induced in Sprague-Dawley rats by feeding HFD for 16 weeks. The rats were randomly divided into 3 groups: control, HFD, and HFD treated with STS (10 mg/kg/day for 12 weeks, intraperitoneal injection). Erectile function including intracavernosal pressure (ICP), H2S production, and antioxidant capacity was assessed. In addition, cavernosal smooth muscle cells (CSMC) isolated from SD rats were pretreated with STS in vitro and exposed to H2O2. Expressions of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), activity of antioxidant enzymes, and H2S-generating enzymes within CSMC were examined. ICP was significantly decreased in HFD rats compared with control. In addition, decreased H2S production and expression of cystathionine ɣ-lyase (CSE) and cystathionine β-synthase (CBS) associated with increased oxidative stress were observed in the penile tissue of HFD rats. However, all these changes were reversed by 16 weeks after STS administration. STS also increased antioxidant defense as evidenced by increased expression of Nrf2/HO-1 in the penile tissue of HFD rats. In CSMC, pretreatment with STS attenuated the decreased expression of CSE and CBS and H2S production by H2O2. STS exerted similar protective antioxidative effect as shown in the in vivo hyperlipidemia model. The present study demonstrated the redox effect of STS treatment on ED via increased H2S production in HFD-induced hyperlipidemia rat model by increased antioxidant capacity via activation of the Nrf2/HO-1 pathway, which provides STS potential clinical application in the treatment of hyperlipidemia-related ED.

Role of hydrogen sulfide in the male reproductive system

“…A complex mechanism by which H 2 S relaxes smooth muscles in the penis may involve activating BKCa and Kv channels, inhibiting RhoA/ROCK signaling pathways, and raising cGMP levels to bypass NO pathway. Recently, selective b3 agonists such as mirabegron (75) and natural extracts such as RVT (79) and STS (77) have been shown to improve ED, with both classes of compounds being at least partly dependent on H 2 S. Besides, the relaxation of bladder smooth muscle by H 2 S has been shown to improve LUTS and subsequent ED. Consequently, the multifaceted therapeutic benefits of H 2 S offer potential for reducing medication dosages and enhancing the quality of life for patients with both conditions.…”

“…ED has been associated with defects in the L-Cys/H 2 S pathway (76). The levels of H 2 S synthases are decreased to varying degrees in the penile tissues of rats with ED caused by radical prostatectomy, hyperlipidemia, diabetes, or hypertension (27,42,44,77). This phenomenon suggests that ED can be treated with exogenous H 2 S supplementation.…”

Therapeutic Potential of Hydrogen Sulfide in Reproductive System Disorders

“…An injury to one or more parts of the penis can result in erectile dysfunction (ED). It has been determined that rats with ED due to radical prostatectomy, hyperlipidemia, diabetes, or hypertension have reduced levels of H 2 S-generating enzyme in their penile tissues [19,51,68,69]. Furthermore, La Fuente et al reported that ED is associated with defects in the L-cysteine/H 2 S pathway [70].…”

“…It appears that RVT-stimulated CC relaxation is partly dependent on H 2 S production and is not dependent on NO production. Furthermore, it was discovered that sodium tanshinone IIA sulfonate (STS) [69] reversed the downregulation of CBS and CSE and inhibited H 2 S production in rats fed a high-fat diet (HFD). Additionally, STS guarded against ED through the activation of the Nrf2/HO-1 pathway in response to HFD-induced oxidative stress.…”

Corrigendum to “Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia”

“…In the article titled “Sodium Tanshinone IIA Sulfonate Attenuates Erectile Dysfunction in Rats with Hyperlipidemia” [ 1 ], there was a spelling error in author Qinyu Zeng's name in the author list, where “Qingyu Zeng” should have read “Qinyu Zeng.” This is corrected as shown above.…”