Inhalative as well as Intravenous Administration of H<sub>2</sub>S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats’ Retina
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<sub>2</sub>S) is considered a potentially neuroprotective substance, b...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/10/5519 |
| Summary: | 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<sub>2</sub>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<sub>2</sub>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<sub>2</sub>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<sub>2</sub>S reduced retinal ganglion cell death with a better result from inhalative application. H<sub>2</sub>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<sub>2</sub>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<sub>2</sub>S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H<sub>2</sub>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<sub>2</sub>S and intravenous GYY 4137 administrations can improve neuronal cell survival. |
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| ISSN: | 1661-6596 1422-0067 |