6.6 Testicular protective effect of hydrogen sulfide
Testicular torsion is a urological emergency that occurs in children and requires immediate surgical treatment; however, despite successful surgical intervention, the incidence of associated complications (such as testicular atrophy and infertility) ranges from 40-60%[179, 180]. Postoperative I/R injury is the main cause of testicular damage, and previous studies have demonstrated that testicular I/R injury is closely related to excessive production of ROS, with subsequent massive production of inflammatory factors, oxidative stress, and apoptosis further exacerbating tissue damage[181, 182]. The subsequent high production of inflammatory factors, oxidative stress and apoptosis further aggravate the tissue damage. In the last two years, studies have revealed that H2S may have potential therapeutic effects in protecting testicular tissue[183, 184]. Bozkurt et al. first investigated the role of H2S in I/R injury in testicular torsion and found that H2S administration inhibited oxidative stress and suppressed the expression of TNF-α, Apaf-1, and iNOS to reduce tissue damage[184]. MPO, MDA and AOPP are markers of lipid peroxidation, and Yuksel et al. found that NaHS could effectively reduce the expression levels of MPO and AOPP. Meanwhile, Johnson scores were significantly higher in the H2S administration group, suggesting that H2S can improve spermatogenic function in I/R-injured testes[183].However, there are still relatively few related studies, and the mechanism of the protective effect of H2S in testicular I/R injury is still unclear, and we need to conduct more in-depth studies.
DisscussionA growing body of evidence suggests that reasonable concentrations of hydrogen sulfide may play a powerful organ-protective role in ischemia-reperfusion injury, possibly acting primarily through mechanisms such as anti-apoptosis, modulation of autophagy, and inhibition of oxidative stress and inflammation. The growing understanding of the important biological effects of H2S, such as vasodilatory, cytoprotective antioxidant and anti-inflammatory effects, as well as its signaling pathway mechanisms, has facilitated the translation of the highly promising cytoprotective functions of H2S into more viable clinical therapeutic modalities. Key to this is the effective design of H2S donors to deliver the desired therapeutic effects. As discussed earlier, designing stable, controlled H2S donors that maintain a stable and slow release of H2S over time is preferable for clinical applications, and much of the physiological utility of H2S is derived from its redox properties. The uncontrolled and rapid release of H2S donors rapidly alters the redox state of cells, and this alteration has a much greater impact on cells than its beneficial physiological functions. With rapidly increasing H2S concentrations, the distribution of each different oxidation state sulfide is very different from the normal physiological state, yet each sulfide has its own unique physiological properties. The volatility of H2S and its rapid metabolism make the development of H2S donors uniquely challenging compared to the development of other small molecule donors, which are highly volatile and are always in a dynamic volatile-soluble equilibrium. In addition, many of the current H2S donors are polysulfides, both the donor itself and the by-products of H2S fraction production, so it is often difficult to distinguish whether the physiological effects of such donors are derived from H2S or other polysulfides. another difficulty in H2S research is how to quantify the range of endogenous H2S concentrations during human circulation and the changes in H2S concentrations during treatment. This is mainly due to the reactive chemical nature of H2S and the complex environment of sulfides in vivo. The inability to accurately monitor H2S concentrations in the circulatory system or target organs will make it difficult to assess the exact relationship between H2S and physiological effects. Therefore, it is important to develop methods that can quantitatively detect H2S concentrations in vivo for H2S research. In conclusion, although sulfide generators have not been new drugs to date, there is precedent for reducing metabolism and thus providing protection against I/R injury in humans. For example, hypothermia therapy has been shown to be beneficial for outcomes in a variety of situations, including out-of-hospital cardiac arrest and during myocardial revascularization. Although there are still many issues that need to be addressed, and these critical issues must be resolved to move into clinical treatment. However, future multidisciplinary collaborations involving nanomaterials, chemistry, pharmaceutical and biological disciplines may finally offer a possibility for H2S therapy, and we look forward to seeing more interesting studies in this area.