OP26 Renal injury induced by nitric oxide depletion is prevented by concomitant inhibition of hydrogen sulfide and/or carbon monoxide production

Nitric Oxide ◽  
2013 ◽  
Vol 31 ◽  
pp. S30-S31
Author(s):  
Sebastiaan Wesseling ◽  
Joost O. Fledderus ◽  
Marianne C. Verhaar ◽  
Jaap A. Joles
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Renal Injury

Abstract 493: Renal Injury Induced by Nitric Oxide Depletion is Prevented by Concomitant Inhibition of Hydrogen Sulfide and/or Carbon Monoxide Production

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Marianne C Verhaar ◽  
Jaap A Joles
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Carbon Monoxide ◽  
Renal Function ◽  
Hydrogen Sulfide ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
No Synthase ◽  
Heme Oxygenase 1 ◽  
Plasma Urea

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Hydrogen sulfide (H 2 S) producing cystathionine-γ-lyase (CSE) and carbon monoxide (CO) producing heme oxygenase-1 (HO-1) appear to be protective in mechanically-induced renal injury (e.g. ischemia reperfusion). However, inhibition of CSE can reduce drug-induced renal injury (e.g. cisplatin). The role of renal H 2 S and HO-1 during chronic NO depletion is unknown. We hypothesized that renal injury secondary to NO depletion via inhibition of NO synthase is diminished by additional H 2 S depletion via inhibition of CSE. Rats (n=6/group) were treated with inhibitors of NO synthase (L-nitroarginine; LNNA), CSE (DL-propargylglycine; PAG), or HO-1 (Sn(IV) protoporphyrin IX dichloride; SnPP) for 1 or 4 weeks or with combinations (LNNA+PAG; LNNA+SnPP; PAG+SnPP or LNNA+PAG+SnPP) for 4 weeks. One week LNNA reduced urinary NOx excretion (35±2% vs baseline) and induced hypertension (173±12 vs. 137±3 mmHg; P<0.01) but renal function remained normal. Four weeks of LNNA further reduced NOx (7±1%), worsened hypertension (223±10 mmHg) and caused renal injury; plasma urea (17±4 vs 7±1 mmol/L; P<0.05), proteinuria (144±35 vs 17±2 mg/d; P<0.01). PAG or SnPP had no effect. NOx was reduced by PAG and increased by SnPP. Renal H 2 S production was completely blocked by PAG and enhanced by SnPP at 1 and 4 weeks. Renal HO-1 expression was induced by LNNA at 4 weeks and by PAG and SnPP at 1 and 4 weeks (all P<0.001). Adding PAG, SnPP, or both, to LNNA did not affect hypertension but preserved renal function. Combining PAG and SnPP had no effect on blood pressure or renal function. Reduction of urine NOx by LNNA was not affected by additional PAG (8±2%) but was ameliorated by adding SnPP (37±4%) or PAG+SnPP (42±9%). Renal H 2 S production was completely inhibited with all PAG-combinations (P<0.01), but was twofold enhanced by LNNA+SnPP (P<0.01). Renal HO-1 expression was increased by all combinations. NO depletion resulted in hypertension and progressive renal injury that was prevented by concomitant inhibition of CSE and/or HO-1. Depletion of H 2 S and CO in the absence of NO depletion had no effect on blood pressure and renal function. These data suggest that pathways from NO depletion to renal injury run via H 2 S or CO.

NO, CO and H2S based pharmaceuticals in the mission of vision (eye health): a comprehensive review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jan Mohammad Mir ◽  
Ram Charitra Maurya ◽  
Mohd Washid Khan
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Human Physiology ◽  
Hydrogen Sulfide ◽  
The Other ◽  
Normal Functioning ◽  
Comprehensive Review ◽  
Molecular Systems ◽  
Eye Health ◽  
Highly Sensitive

Abstract A set of well defined signaling molecules responsible for normal functioning of human physiology including nitric oxide along with carbon monoxide and hydrogen sulphide are referred as “gasotransmitters”. Due to their involvement in almost every system of a human body, the care of highly sensitive organs using these molecules as drugs represents highly fascinating area of research. In connection with these interesting aspects, the applied aspects of these gaseous molecules in maintaining healthy eye and vision have been targeted in this review. Several examples of eye-droppers including NORMs like latanoprost and nipradiol, CORMs like CORM-3 and CORM-A1, and Hydrogen sulfide releasing system like GYY4137 have been discussed in this context. Therefore the relation of these trio-gasotransmitters with the ophthalmic homeostasis on one hand, and de-infecting role on the other hand has been mainly highlighted. Some molecular systems capable of mimicking gasotransmitter action have also been introduced in connection with the titled theme.

scholarly journals The Role of Host-Generated H2S in Microbial Pathogenesis: New Perspectives on Tuberculosis

2020 ◽  
Vol 10 ◽  
Author(s):  
Md. Aejazur Rahman ◽  
Joel N. Glasgow ◽  
Sajid Nadeem ◽  
Vineel P. Reddy ◽  
Ritesh R. Sevalkar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Host Immunity ◽  
Microbial Pathogens ◽  
Microbial Pathogenesis ◽  
Enzymatic Production ◽  
Growth And Survival ◽  
Wide Range

For centuries, hydrogen sulfide (H2S) was considered primarily as a poisonous gas and environmental hazard. However, with the discovery of prokaryotic and eukaryotic enzymes for H2S production, breakdown, and utilization, H2S has emerged as an important signaling molecule in a wide range of physiological and pathological processes. Hence, H2S is considered a gasotransmitter along with nitric oxide (•NO) and carbon monoxide (CO). Surprisingly, despite having overlapping functions with •NO and CO, the role of host H2S in microbial pathogenesis is understudied and represents a gap in our knowledge. Given the numerous reports that followed the discovery of •NO and CO and their respective roles in microbial pathogenesis, we anticipate a rapid increase in studies that further define the importance of H2S in microbial pathogenesis, which may lead to new virulence paradigms. Therefore, this review provides an overview of sulfide chemistry, enzymatic production of H2S, and the importance of H2S in metabolism and immunity in response to microbial pathogens. We then describe our current understanding of the role of host-derived H2S in tuberculosis (TB) disease, including its influences on host immunity and bioenergetics, and on Mycobacterium tuberculosis (Mtb) growth and survival. Finally, this review discusses the utility of H2S-donor compounds, inhibitors of H2S-producing enzymes, and their potential clinical significance.

scholarly journals Do nitric oxide, carbon monoxide and hydrogen sulfide really qualify as ‘gasotransmitters’ in bacteria?

2018 ◽  
Vol 46 (5) ◽  
pp. 1107-1118 ◽  
Author(s):  
Lauren K. Wareham ◽  
Hannah M. Southam ◽  
Robert K. Poole
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Small Molecule ◽  
Toxic Effects ◽  
Gaseous Molecule ◽  
Recent Advances ◽  
Definition Of

A gasotransmitter is defined as a small, generally reactive, gaseous molecule that, in solution, is generated endogenously in an organism and exerts important signalling roles. It is noteworthy that these molecules are also toxic and antimicrobial. We ask: is this definition of a gasotransmitter appropriate in the cases of nitric oxide, carbon monoxide and hydrogen sulfide (H2S) in microbes? Recent advances show that, not only do bacteria synthesise each of these gases, but the molecules also have important signalling or messenger roles in addition to their toxic effects. However, strict application of the criteria proposed for a gasotransmitter leads us to conclude that the term ‘small molecule signalling agent’, as proposed by Fukuto and others, is preferable terminology.

scholarly journals Hydrogen sulphide synthesis (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Timothy R. Billiar ◽  
Giuseppe Cirino ◽  
David Fulton ◽  
Roberto Motterlini ◽  
Andreas Papapetropoulos ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide ◽  
Hydrogen Sulphide ◽  
Pyridoxal Phosphate ◽  
Enzymatic Activities ◽  
Pharmacological Modulation ◽  
Enzymatic Characteristics ◽  
Mercaptopyruvate Sulfurtransferase ◽  
Cytosolic Enzymes

Hydrogen sulfide is a gasotransmitter, with similarities to nitric oxide and carbon monoxide. Although the enzymes indicated below have multiple enzymatic activities, the focus here is the generation of hydrogen sulphide (H2S) and the enzymatic characteristics are described accordingly. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are pyridoxal phosphate (PLP)-dependent enzymes. 3-mercaptopyruvate sulfurtransferase (3-MPST) functions to generate H2S; only CAT is PLP-dependent, while 3-MPST is not. Thus, this third pathway is sometimes referred to as PLP-independent. CBS and CSE are predominantly cytosolic enzymes, while 3-MPST is found both in the cytosol and the mitochondria. For an authoritative review on the pharmacological modulation of H2S levels, see Szabo and Papapetropoulos, 2017 [4].

Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide

2012 ◽  
Vol 184 (2) ◽  
pp. 117-129 ◽  
Author(s):  
Kenneth R. Olson ◽  
John A. Donald ◽  
Ryan A. Dombkowski ◽  
Steve F. Perry
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Hydrogen Sulfide
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