scholarly journals Proteomics Reveals the Potential Protective Mechanism of Hydrogen Sulfide on Retinal Ganglion Cells in an Ischemia/Reperfusion Injury Animal Model

2020 ◽  
Vol 13 (9) ◽  
pp. 213
Author(s):  
Hanhan Liu ◽  
Natarajan Perumal ◽  
Caroline Manicam ◽  
Karl Mercieca ◽  
Verena Prokosch
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Iron Homeostasis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Differentially Expressed ◽  
Protective Mechanism ◽  
Retinal Ganglion ◽  
Sprague Dawley

Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) degeneration. Hydrogen sulfide (H2S) is a potent neurotransmitter and has been proven to protect RGCs against glaucomatous injury in vitro and in vivo. This study is to provide an overall insight of H2S’s role in glaucoma pathophysiology. Ischemia-reperfusion injury (I/R) was induced in Sprague-Dawley rats (n = 12) by elevating intraocular pressure to 55 mmHg for 60 min. Six of the animals received intravitreal injection of H2S precursor prior to the procedure and the retina was harvested 24 h later. Contralateral eyes were assigned as control. RGCs were quantified and compared within the groups. Retinal proteins were analyzed via label-free mass spectrometry based quantitative proteomics approach. The pathways of the differentially expressed proteins were identified by ingenuity pathway analysis (IPA). H2S significantly improved RGC survival against I/R in vivo (p < 0.001). In total 1115 proteins were identified, 18 key proteins were significantly differentially expressed due to I/R and restored by H2S. Another 11 proteins were differentially expressed following H2S. IPA revealed a significant H2S-mediated activation of pathways related to mitochondrial function, iron homeostasis and vasodilation. This study provides first evidence of the complex role that H2S plays in protecting RGC against I/R.

Intravenous bilirubin provides incomplete protection against renal ischemia-reperfusion injury in vivo

2007 ◽  
Vol 292 (2) ◽  
pp. F888-F894 ◽  
Author(s):  
Kristin Kirkby ◽  
Chris Baylis ◽  
Anupam Agarwal ◽  
Byron Croker ◽  
Linda Archer ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Rat Kidney ◽  
Ischemia Reperfusion ◽  
Renal Plasma Flow ◽  
In Vivo Model ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Organ Systems

Exogenous bilirubin (BR) substitutes for the protective effects of heme oxygenase (HO) in several organ systems. Our objective was to investigate the effects of exogenous BR in an in vivo model of ischemia-reperfusion injury (IRI) in the rat kidney. Four groups of male Sprague-Dawley rats were anesthetized using isoflurane in oxygen and treated with 1) 5 mg/kg intravenous (iv) BR, 1 h before ischemia and 6-h reperfusion; 2) vehicle 1 h before ischemia and 6-h reperfusion; 3) 20 mg/kg iv BR, 1 h before and during ischemia; and 4) vehicle 1 h before and during ischemia. Bilateral renal clamping (30 min) was followed by 6-h reperfusion. Infusion of 5 mg/kg iv BR achieved target levels in the serum at 6 h postischemia (31 ± 9 μmol/l). Infusion of 20 mg/kg BR reached 50 ± 22 μmol/l at the end of ischemia, and a significant improvement was seen in serum creatinine at 6 h (1.07 ± 28 vs. 1.38 ± 0.18 mg/dl, P = 0.043). Glomerular filtration rate, estimated renal plasma flow, fractional excretion of electrolytes, and renal vascular resistance were not significantly improved in BR-treated groups. Histological grading demonstrated a trend toward preservation of cortical proximal tubules in rats receiving 20 mg/kg iv BR compared with control; however, neither BR dose provided protection against injury to the renal medulla. At the doses administered, iv BR did not provide complete protection against IRI in vivo. Combined supplementation of both BR and carbon monoxide may be required to preserve renal blood flow and adequately substitute for the protective effects of HO in vivo.

Therapeutic Metabolic Inhibition: Hydrogen Sulfide Significantly Mitigates Skeletal Muscle Ischemia Reperfusion Injury In Vitro and In Vivo

2010 ◽  
Vol 126 (6) ◽  
pp. 1890-1898 ◽  
Author(s):  
Peter W. Henderson ◽  
Sunil P. Singh ◽  
Andrew L. Weinstein ◽  
Vijay Nagineni ◽  
Daniel C. Rafii ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Metabolic Inhibition ◽  
Muscle Ischemia

Ischemia-reperfusion reduces cystathionine-β-synthase-mediated hydrogen sulfide generation in the kidney

2009 ◽  
Vol 297 (1) ◽  
pp. F27-F35 ◽  
Author(s):  
Zhibin Xu ◽  
Gamika Prathapasinghe ◽  
Nan Wu ◽  
Sun-Young Hwang ◽  
Yaw L. Siow ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Left Kidney ◽  
Kidney Tissue ◽  
Sprague Dawley ◽  
Transsulfuration Pathway

Cystathionine-β-synthase (CBS) catalyzes the rate-limiting step in the transsulfuration pathway for the metabolism of homocysteine (Hcy) in the kidney. Our recent study demonstrates that ischemia-reperfusion reduces the activity of CBS leading to Hcy accumulation in the kidney, which in turn contributes to renal injury. CBS is also capable of catalyzing the reaction of cysteine with Hcy to produce hydrogen sulfide (H2S), a gaseous molecule that plays an important role in many physiological and pathological processes. The aim of the present study was to examine the effect of ischemia-reperfusion on CBS-mediated H2S production in the kidney and to determine whether changes in the endogenous H2S generation had any impact on renal ischemia-reperfusion injury. The left kidney of Sprague-Dawley rat was subjected to 45-min ischemia followed by 6-h reperfusion. The ischemia-reperfusion caused lipid peroxidation and cell death in the kidney. The CBS-mediated H2S production was decreased, leading to a significant reduction in the renal H2S level. The activity of cystathionine-γ-lyase, another enzyme responsible for endogenous H2S generation, was not significantly altered in the kidney upon ischemia-reperfusion. Partial restoration of CBS activity by intraperitoneal injection of the nitric oxide scavenger, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide not only increased renal H2S levels but also alleviated ischemia-reperfusion-induced lipid peroxidation and reduced cell damage in the kidney tissue. Furthermore, administration of an exogenous H2S donor, NaHS (100 μg/kg), improved renal function. Taken together, these results suggest that maintenance of tissue H2S level may offer a renal protective effect against ischemia-reperfusion injury.

Hydrogen Sulfide Attenuates Ischemia-Reperfusion Injury in In Vitro and In Vivo Models of Intestine Free Tissue Transfer

2010 ◽  
Vol 125 (6) ◽  
pp. 1670-1678 ◽  
Author(s):  
Peter W. Henderson ◽  
Andrew L. Weinstein ◽  
Josephine Sung ◽  
Sunil P. Singh ◽  
Vijay Nagineni ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Free Tissue Transfer ◽  
In Vivo Models ◽  
Tissue Transfer

scholarly journals Hydrogen Sulfide Reduces Ischemia and Reperfusion Injury in Neuronal Cells in a Dose- and Time-Dependent Manner

2021 ◽  
Vol 22 (18) ◽  
pp. 10099
Author(s):  
Stefanie Scheid ◽  
Max Goeller ◽  
Wolfgang Baar ◽  
Jakob Wollborn ◽  
Hartmut Buerkle ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Reperfusion Injury ◽  
Inflammatory Cytokines ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Retinal Ganglion ◽  
Ischemia And Reperfusion Injury ◽  
Cell Counts ◽  
Tnf Α

Background: The ischemia-reperfusion injury (IRI) of neuronal tissue, such as the brain and retina, leads to possible cell death and loss of function. Current treatment options are limited, but preliminary observations suggest a protective effect of hydrogen sulfide (H2S). However, the dosage, timing, and mechanism of inhaled H2S treatment after IRI requires further exploration. Methods: We investigated possible neuroprotective effects of inhaled H2S by inducing retinal ischemia–reperfusion injury in rats for the duration of 1 h (120 mmHg), followed by the administration of hydrogen sulfide (H2S) for 1 h at different time points (0, 1.5, and 3 h after the initiation of reperfusion) and at different H2S concentrations (120, 80, and 40 ppm). We quantified the H2S effect by conducting retinal ganglion cell counts in fluorogold-labeled animals 7 days after IRI. The retinal tissue was harvested after 24 h for molecular analysis, including qPCR and Western blotting. Apoptotic and inflammatory mediators, transcription factors, and markers for oxidative stress were investigated. Histological analyses of the retina and the detection of inflammatory cytokines in serum assays were also performed. Results: The effects of inhaled H2S were most evident at a concentration of 80 ppm administered 1.5 h after IRI. H2S treatment increased the expression of anti-apoptotic Bcl-2, decreased pro-apoptotic Bax expression, reduced the release of the inflammatory cytokines IL-1β and TNF-α, attenuated NF-κB p65, and enhanced Akt phosphorylation. H2S also downregulated NOX4 and cystathionine β-synthase. Histological analyses illustrated a reduction in TNF-α in retinal ganglion cells and lower serum levels of TNF-α in H2S-treated animals after IRI. Conclusion: After neuronal IRI, H2S mediates neuroprotection in a time- and dose-dependent manner. The H2S treatment modulated transcription factor NF-κB activation and reduced retinal inflammation.

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