Article ; Online: Inhalative as well as Intravenous Administration of H 2 S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats’ Retina
International Journal of Molecular Sciences, Vol 23, Iss 5519, p
2022 Volume 5519
Abstract: Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H 2 S) is considered a potentially ... ...
| Abstract | Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H 2 S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined. Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H 2 S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H 2 S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia. Results: Both inhalative and intravenously delivered H 2 S reduced retinal ganglion cell death with a better result from inhalative application. H 2 S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H 2 S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H 2 S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H 2 S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase. Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H 2 S and intravenous GYY 4137 administrations can improve neuronal cell survival. |
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| Keywords | hydrogen sulfide ; H 2 S ; GYY 4137 ; ischemia-reperfusion injury ; apoptosis ; inflammation ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999 |
| Subject code | 610 |
| Language | English |
| Publishing date | 2022-05-01T00:00:00Z |
| Publisher | MDPI AG |
| Document type | Article ; Online |
| Database | BASE - Bielefeld Academic Search Engine (life sciences selection) |
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