Hydrogen Sulfide: A Therapeutic Option in Systemic Sclerosis

Abstract

Systemic sclerosis (SSc) is a lethal disease that is characterized by auto-immunity, vascular injury, and progressive fibrosis of multiple organ systems. Despite the fact that the exact etiology of SSc remains unknown, oxidative stress has been associated with a large range of SSc-related complications. In addition to the well-known detrimental properties of reactive oxygen species (ROS), gasotransmitters (e.g., nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)) are also thought to play an important role in SSc. Accordingly, the diverse physiologic actions of NO and CO and their role in SSc have been previously studied. Recently, multiple studies have also shown the importance of the third gasotransmitter H2S in both vascular physiology and pathophysiology. Interestingly, homocysteine (which is converted into H2S through the transsulfuration pathway) is often found to be elevated in SSc patients; suggesting defects in the transsulfuration pathway. Hydrogen sulfide, which is known to have several effects, including a strong antioxidant and vasodilator effect, could potentially play a prominent role in the initiation and progression of vasculopathy. A better understanding of the actions of gasotransmitters, like H2S, in the development of SSc-related vasculopathy, could help to create early interventions to attenuate the disease course. This paper will review the role of H2S in vascular (patho-)physiology and potential disturbances in SSc. Moreover, current data from experimental animal studies will be reviewed. Lastly, we will evaluate potential interventional strategies.

SG1002 and Catenated Divalent Organic Sulfur Compounds as Promising Hydrogen Sulfide Prodrugs

“…Further, Szabo and Papapetropoulos rightly point out that not only H 2 S-poor diseases can be corrected by H 2 S supplementation, since ''there are also several indications where endogenous H 2 S levels are not suppressed, and yet H 2 S donation may be beneficial or warranted.'' Additional evidence, obtained mainly after the list just cited was compiled, supports considering therapeutic application of H 2 S prodrugs in cancer (148), psoriasis (12), multiple viral infections (24,25), colitis (180), autoimmune pathologies (42), systemic sclerosis (2), multiple sclerosis (245), Parkinson's disease (PD) (111), intracerebral hemorrhage (288), Duchenne muscular dystrophy/cardiomyopathy (44), allergic diseases (173), fibrotic disorders (229), osteoarthritis (164), osteoporosis (281), sarcopenia (32), pulmonary hypertension (287), ocular hypertension (225), kidney diseases (15), hearing loss (152), lens opacification (190), testicular dysfunction (262), male subfertility (178), erectile dysfunction (64), and periodontitis (89) as well.…”

N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019

“…Another H 2 S-synthesizing pathway exists primarily in mitochondria, and is a cysteine catabolic pathway mediated by cysteine aminotransferase (CAT) and 3-mercaptopyruvate sulfurtransferase . Finally, production of H 2 S can also occur nonenzymatically through reductive chemistry of various sulfur species, including thiosulfate, thiocystine, and sulfite, although these mechanisms are less well understood and account for only a small part of H 2 S production (1). Recently, however, another nonenzymatic H 2 S-generating mechanism has been described, which involves a nonenzymatic catalysis of cysteine by coordinated action of iron (Fe 3+ form) and PLP (110).…”

Intimate intertwining of the pathogenesis of hypoxia and systemic sclerosis: A transcriptome integration analysis

“…It has multiple but unclear pathogenic mechanisms, including genetic and environmental factors ( 15 ). An imbalance between the oxidant and anti-oxidant states has been suggested to initiate SSc ( 16 , 17 ). Hypoxia is involved in SSc pathogenesis by inducing oxidative stress ( 4 ).…”