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

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.

Phosphinodithioate and Phosphoramidodithioate Hydrogen Sulfide Donors

“…In the CFA arthritis model ), CFA injection induced synovial H 2 S synthesis fluid (SF), in agreement with in vitro studies using human joint cells Fox et al 2012;Burguera et al 2014) and observations with human SF from patients with various inflammatory arthritides (Whiteman and Winyard 2011;Whiteman et al 2010c). GYY4137 (50 mg/kg i.p.)…”

“…The ratio of blood/sputum H 2 S levels has been proposed as a novel biomarker for airway disease (Chung 2014;Saito et al 2013Saito et al , 2014Wang et al 2011a). Similarly, synovial fluid H 2 S levels are elevated relative to disease controls in patients with rheumatoid arthritis (Whiteman et al 2010c) and inflammatory joint disease (Whiteman and Winyard 2011). Early studies generally showed inhibition of endogenous H 2 S synthesis attenuated pro-inflammatory signalling in vitro and inflammation in vivo (reviewed in Whiteman and Winyard (2011)), although it should be noted that pharmacological inhibitors of CSE, CBS and 3-MST are non-specific necessitating their use at very high concentrations (reviewed in detail in ) and the addition of NaSH to cultured cells in vitro (Whiteman et al 2010b;Zhang et al 2008;Zhi et al 2007;Kloesch et al 2012a, b).…”

Endogenous Hydrogen Sulfide Ameliorates NOX4 Induced Oxidative Stress in LPS-Stimulated Macrophages and Mice

“…Over the years, H 2 S is emerging as an important mediator in acute and chronic inflammation [8]. It has been reported that the increased H 2 S circulation detected in the burn injury [36] and its levels correlated with inflammatory and clinical indices in rheumatoid arthritis patients [37]. Moreover, multiple lines of studies, in multiple experimental models, showing that therapeutic elevation of H 2 S concentrations or H 2 S donors can exert anti-inflammation and decrease the mortality caused by endotoxemia [38][39][40].…”

Análise farmacológica comparativa da pancreatite experimental induzida por fosfolipase A₂secretória do veneno de serpente <i>Crotalus durissus terrificus</i> e fosfolipase A₂ de mamífero em ratos: papel das fibras C e do sulfeto de hidrogênio.

“…Dentre os doadores de H 2 S disponíveis comercialmente, empregados em modelos inflamatórios e sensitivos, estão os doadores de H 2 S de liberação espontânea/rápida: hidrossulfeto de sódio (NaHS), sulfeto de sódio (Na 2 S), o reagente de Lawesson, os de liberação lenta (Benetti et al, 2013;Campos et al, 2016;Coavoy-Sánchez et al, 2016;Ekundi et al, 2010;Li et al, 2009;Rodrigues et al, 2016;Wang, 2012;Whiteman et al, 2010;) e os doadores híbridos (H 2 S associado a uma molécula anti-inflamatória não esteroide; Ekundi-Valentim et al, 2013;Gemici et al, 2015).…”

“…Postula-se que as ações tóxicas/deletérias do H 2 S descritas em alguns estudos podem ser explicadas pelo fato que a taxa de liberação de H 2 S dos doadores espontâneos/rápidos, como o NaHS, é extremamente alta e em curto período de tempo, enquanto a taxa de liberação de H 2 S por GYY4137 é muito menor (cerca de 200 X), mas de forma constante e prolongada (Whiteman et al, 2010), mimetizando assim a liberação de H 2 S endógeno em sistemas fisiológicos. Em concentrações fisiológicas, o H 2 S causa relaxamento muscular por ação direta em canais de K ATP , assim como intensifica a ação relaxante do óxido nítrico (Wang et al, 2014).…”