Background: Hydrogen sulfide (H₂S) is an endogenously produced gaseous neurotransmitter. H₂S donors exhibited neuroprotection in oxidative-stress-related disorders in preclinical studies, but odor and short half-lives have limited their clinical use. However, endogenous H₂S stimulators with antioxidant properties have advantages over H₂S donors regarding safety and patient compliance. Empagliflozin (EMPA), a sodium–glucose cotransporter-2 (SGLT2) inhibitor widely used in the treatment of diabetes mellitus (DM), exerted similar neuroprotective and antioxidant effects as H₂S and shares common mechanisms. This study aimed to investigate the role of H₂S in the antioxidant effects of EMPA in the brain. Methods: The effects of EMPA on H₂S production and reactive oxygen species (ROS) formation were assessed ex vivo in mouse brain under normal conditions and pyrogallol-induced oxidative stress. Moreover, rats were divided into the following four groups: nondiabetic, EMPA-treated nondiabetic, streptozotocin (STZ)-induced diabetic, and EMPA-treated, STZ-induced diabetic. Endogenous H₂S and ROS levels in the brain were measured using methylene blue and chemiluminescence assays, respectively. Results: Ex vivo EMPA treatment significantly increased endogenous H₂S formation in both healthy and pyrogallol-induced oxidative stress, as well as reduced ROS formation in mouse brain; these effects were significantly reversed by the H₂S synthesis inhibitor aminooxyacetic acid (AOAA). Oral EMPA administration significantly elevated brain H₂S levels in both nondiabetic and diabetic rats and reduced ROS formation. These effects were inhibited by AOAA. Conclusions: Our study revealed a novel mechanism by which EMPA can reduce oxidative stress in neurodegenerative disorders by triggering H₂S synthesis in the brain.

Metformin is an antidiabetic drug that is widely used in the treatment of type 2 diabetes mellitus (T2DM) and is known to reduce oxidative stress. Drug-loaded niosomes enhance the cellular uptake of drugs, resulting in improved antioxidant effects. In this study, we formulated metformin-loaded niosomes, aiming to enhance cellular drug uptake and augment antioxidant effects. The particle size, polydispersity index, and zeta potential values were found to be 153.8 nm, 0.449, and −9.32 mV respectively. Morphological observations conducted through scanning electron microscopy (SEM) provided insights into the distinctive structure of the niosomes. Entrapment efficiency of drug-loaded niosomes was determined to be 68%. In vitro drug release studies, performed by using the dialysis bag method, exhibited a release profile consistent with Hixson–Crowell kinetics. After characterization of the formulations, the antioxidant activity of metformin-loaded niosomes on Pyrogallol-induced reactive oxygen species (ROS) formation in the mouse brain was compared with metformin treatment alone. ROS formation was measured by a luminol–lucigenin chemiluminescence assay. Metformin-loaded niosomes significantly reduced ROS formation compared to metformin treatment alone. Metformin-loaded niosomes offer potential for enhanced antioxidant effects and bioavailability by increasing cellular uptake of metformin.

Purpose: Ischemic priapism (IP) is characterised by prolonged, painful erections that require urgent intervention to prevent corporal fibrosis and erectile dysfunction. Hydrogen sulfide (H₂S), a gaseous mediator, has been shown to exert protective effects against ischemia-reperfusion (IR) injury by reducing oxidative stress, enhancing mitochondrial function, and inhibiting apoptosis. This study aimed to investigate the role of H₂S during IP and reperfusion and its potential protective effects against penile tissue injury. Methods: Twenty-eight male Wistar rats were divided into four groups: control, IP, IP-R, and IP-[NaHS]-R. The control group underwent penectomy only. In the IP group, penectomy was performed after 4 h of priapism, whereas in the IP-R group, it was performed after 4 h of priapism followed by 1 h of reperfusion. In the IP-[NaHS]-R group, rats received NaHS (75 µmol/kg, intraperitoneally) 10 min before reperfusion. Endogenous H₂S levels were determined by the methylene blue assay, and hypoxia-inducible factor-1α (HIF-1α) expression was evaluated by immunohistochemistry. Results: Histopathological analyses were performed to assess tissue alterations. The IP and IP-R groups showed edema, inflammation, desquamation, vasocongestion, and increased collagen deposition, and exhibited reduced H₂S levels ( p < 0.05) and elevated HIF-1α ( p < 0.0001) compared with control group. NaHS administration increased H₂S levels, reduced HIF-1α expression, and alleviated histopathologic changes. Conclusion: Decreased H₂S levels during ischemia and reperfusion were associated with penile tissue injury in IP. NaHS mitigated morphological damage during the initial phase of reperfusion, indicating the potential involvement of H₂S signaling in reperfusion-related corporal tissue injury. However, endpoints related to the resolution of priapism, such as detumescence time and intracavernosal pressure (ICP), have not been evaluated. These assessments are necessary to determine the translational safety and therapeutic applicability of these treatments in cases of IP.

W w w. a k a d e m i s y e n. c o m UYARI Bu üründe yer alan bilgiler sadece lisanslı tıbbi çalışanlar için kaynak olarak sunulmuştur. Herhangi bir konuda profesyonel tıbbi danışmanlık veya tıbbi tanı amacıyla kullanılmamalıdır. Akademisyen Kitabevi ve alıcı arasında herhangi bir şekilde doktor-hasta, terapist-hasta ve/veya başka bir sağlık sunum hizmeti ilişkisi oluşturmaz. Bu ürün profesyonel tıbbi kararların eşleniği veya yedeği değildir. Akademisyen Kitabevi ve bağlı şirketleri, yazarları, katılımcıları, partnerleri ve sponsorları ürün bilgilerine dayalı olarak yapılan bütün uygulamalardan doğan, insanlarda ve cihazlarda yaralanma ve/veya hasarlardan sorumlu değildir. İlaçların veya başka kimyasalların reçete edildiği durumlarda, tavsiye edilen dozunu, ilacın uygulanacak süresi, yöntemi ve kontraendikasyonlarını belirlemek için, okuyucuya üretici tarafından her ilaca dair sunulan güncel ürün bilgisini kontrol etmesi tavsiye edilmektedir. Dozun ve hasta için en uygun tedavinin belirlenmesi, tedavi eden hekimin hastaya dair bilgi ve tecrübelerine dayanak oluşturması, hekimin kendi sorumluluğundadır. Akademisyen Kitabevi, üçüncü bir taraf tarafından yapılan kitaba dair değişikliklerden sorumlu değildir.