Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review
Abstract
Hydrogen sulfide (H2S) is a gasotransmitter that plays a crucial role in regulating pathological processes following injury to the central and peripheral nervous systems. This review systematizes current data on various classes of H2S donors and inhibitors of its biosynthesis in neurotrauma and related experimental models. Inorganic donors (e.g., NaHS, Na2S, and STS) rapidly suppress oxidative stress and inflammation, supporting the recovery of synaptic plasticity and cognitive function. Organic donors (e.g., GYY4137, ACS67, ACS84, SPRC, ADT-OH and its derivatives, S-memantine, and MTC) provide sustained H2S release, stabilize the blood-brain barrier, and exhibit antiapoptotic activity. Natural donors (e.g., DADS, DATS, and SAMe) demonstrate high biocompatibility, inhibit pyroptosis, and enhance antioxidant defense mechanisms. Hybrid systems-including nanoparticles and hydrogels-enable targeted delivery and prolonged action, thereby stimulating regeneration and angiogenesis. Thiol-activated donors (e.g., COS/H2S and AlaCOS) allow controlled H2S release, offering broad opportunities for precise modulation of its concentration within target tissues. Inhibitors (e.g., AOAA, PAG, oxamic hydrazide 1, L-aspartic acid, benserazide, and NSC4056) of H2S biosynthesis underscore the physiological importance of this gasotransmitter, as their administration enhances neuroinflammation and diminishes neuroprotection. The analysis reveals a general pattern: all classes of H2S donors…
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