Detection of hydrogen sulfide in plasma and knee-joint synovial fluid from rheumatoid arthritis patients: relation to clinical and laboratory measures of inflammation.

Institute of Biomedical and Clinical Science, Peninsula Medical School, University of Exeter, St. Luke's Campus, Magdalen Road, Exeter, Devon, UK.
Annals of the New York Academy of Sciences (Impact Factor: 4.31). 08/2010; 1203:146-50. DOI: 10.1111/j.1749-6632.2010.05556.x
Source: PubMed

ABSTRACT Blood concentrations of hydrogen sulfide (H(2)S) are markedly elevated in several animal models of inflammation. Pharmacological inhibition of H(2)S synthesis reduces inflammation and swelling, suggesting that H(2)S is a potential inflammatory mediator. However, it is currently unknown whether H(2)S synthesis is perturbed in human inflammatory conditions or whether H(2)S is present in synovial fluid. We analyzed paired plasma and synovial fluid (SF) aspirates from rheumatoid arthritis (RA; n= 20) and osteoarthritis (OA; n= 4) patients and plasma from age matched healthy volunteers (n= 20). Median plasma H(2)S concentrations from healthy volunteers and RA and OA patients were 37.6, 36.6, and 37.6 microM, respectively. In RA patients, median synovial fluid H(2)S levels (62.4 microM) were significantly higher than paired plasma (P= 0.002) and significantly higher than in synovial fluid from OA patients (25.1 microM; P= 0.009). SF H(2)S levels correlated with clinical indices of disease activity (tender joint count, r= 0.651; P < 0.05) and markers of chronic inflammation; Europhile count (r=-0.566; P < 0.01) and total white cell count (r=-0.703; P < 0.01). Our study shows for the first time that H(2)S is present in synovial fluid and levels correlated with inflammatory and clinical indices in RA patients.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Together with carbon monoxide (CO), nitric oxide (̇NO) and hydrogen sulfide (H2S) form a group of physiologically important gaseous transmitters, sometimes referred to as the "gaseous triumvirate". The three molecules share a wide range of physical and physiological properties: they are small gaseous molecules, able to freely penetrate cellular membranes; they are all produced endogenously in the body and they seem to exert similar biological functions. In the cardiovascular system, for example, they are all vasodilators, promote angiogenesis and protect tissues against damage (e.g. ischemia-reperfusion injury). In addition, they have complex roles in inflammation, with both pro- and anti-inflammatory effects reported. Researchers have focused their efforts in understanding and describing the roles of each of these molecules in different physiological systems, and in the past years attention has also been given to the gases interaction or "cross-talk". This review will focus on the role of ̇NO and H2S in inflammation and will give an overview of the evidence collected so far suggesting the importance of their cross-talk in inflammatory processes.
    Nitric Oxide 06/2014; 41. DOI:10.1016/j.niox.2014.05.014 · 3.18 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A naphthalimide-azide based colorimetric and ratiometric fluorescent probe, NAP-1, has been developed for the selective and sensitive detection of hydrogen sulphide. Advantages of the probe NAP-1 include a low detection limit (110 nM), good selectivity, high sensitivity and excellent photostability. A linear relationship between the emission intensity ratios and sulphide concentrations was observed in PBS buffer and bovine serum, respectively. Our probe facilitates ratiometric determination and imaging of endogenous H2S in living cells. Furthermore, this probe was successfully applied to the measurement of endogenous sulphide in human plasma and mouse hippocampus. A significant reduction in sulphide levels and CBS mRNA expression was observed in the hippocampus of mouse models of lipopolysaccharide-induced neuroinflammation-related diseases, suggesting that decreased levels of endogenous H2S might be involved in the pathogenesis of neuroinflammation-related neurodegenerative diseases.
    Organic & Biomolecular Chemistry 05/2014; 12(28). DOI:10.1039/c4ob00285g · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hydrogen sulfide (H2S) is a gasotransmitter synthesized in peripheral tissues by the enzyme cystathionine gamma-lyase (CSE). This gas has been documented to be involved in a wide variety of processes including inflammation and nociception. The aim of the present study was to investigate the role of the peripheral H2S pathway in nociceptive response to the orofacial formalin experimental model of pain. Orofacial pain was induced by subcutaneous injection of formalin (1.5%, 50 µl) into the upper lip of rats, and the time spent rubbing the face was measured at 3-min intervals for 45 min. Formalin induced a marked biphasic pain (first phase: 0–3 min; second phase: 15–33 min). Pretreatment with H2S donor (Na2S; 90 µmol/kg), CSE inhibitor (propargylglycine; 26.5 and 88.4 µmol/kg), or a preferential blocker of T-type Ca2+ channels (mibefradil; 0.28 and 2.81 µmol/kg) attenuated the second phase of face rubbing when injected locally as well as systemically. Pretreatment with a selective blocker of K+ATP channels (glybenclamide; 2.81 µmol/kg) suppressed the Na2S-mediated attenuation of the formalin-induced pain second phase. Taken together these results suggest that endogenously produced H2S plays a pronociceptive role probably via T-type Ca2+ channels, whereas exogenous H2S exerts antinociceptive effects mediated by K+ATP channels.
    European Journal of Pharmacology 09/2014; 738:49–56. DOI:10.1016/j.ejphar.2014.05.023 · 2.68 Impact Factor