Hydrogen sulphide is a mediator of carrageenan‐induced hindpaw oedema in the rat

Abstract

Hydrogen sulphide (H 2 S) is a naturally occurring gas, with potent vasodilator activity. In this report, we identify a role for H 2 S in carrageenan-induced hindpaw oedema in the rat. Intraplantar injection of carrageenan (150 ml, 2% (w v À1 )) resulted in an increase in hindpaw H 2 S synthesising enzyme activity and increased myeloperoxidase (MPO) activity. Pretreatment (i.p. 60 min before carrageenan) with DL-propargylglycine (PAG, 25-75 mg kg À1 ), an inhibitor of the H 2 S synthesising enzyme cystathionine-g-lyase (CSE), significantly reduced carrageenan-induced hindpaw oedema in a dose-dependent manner (e.g. increase in hindpaw weight at 3 h, saline: 0.1270.017 g; carrageenan, 1.3970.037 g; PAG, 50 mg kg

Hydrogen sulfide as a vasodilator

“…This is a well-established model of joint inflammation. Intraplantar injection of carrageenan in the rat hindpaw resulted in an increase in the H 2 S synthesizing enzyme activity whilst pre-treatment with the CSE-inhibitor DL-propargylglycine (PAG) significantly reduced inflammation in a dosedependent manner in carrageenan-induced hindpaw edema (22).…”

Hydrogen sulfide and inflammation: the good, the bad, the ugly and the promising

“…A closer examination of the experimental protocol used in both studies suggests interlaboratory methodological differences could have accounted for these apparent contradictions. For example, Bhatia et al treated rats with 2% w/v solution of carrageenan for 3 h and added PAG intraplantar into one hindpaw 1 h before carrageenan treatment [40], whereas Zanardo et al performed time-course studies and used a 1.5% w/v solution, injecting BCA (or H 2 S donors) intraperitoneally 30 min prior to carrageenan treatment [41]. It is also possible that BCA and/or PAG exhibited effects independent of CSE inhibition, which modulated hindpaw fluid homeostasis (see later).…”

“…Edema is commonly modeled in the laboratory through the use of carrageenan, a mucopolysaccharide extract of Chondrus crispus that induces an acute, defined and nonimmune inflammatory response [39]. Injection of carrageenan into the hindpaw of rats induced a significant increase in H 2 S synthesis and neutrophil infiltration, whereas pretreatment with PAG (a CSE inhibitor) resulted in dose-dependent inhibition of hindpaw edema and MPO activity [40]. In sharp contrast to this, a more recent study [41] showed the H 2 S 'donors' NaSH, sodium sulfide (Na 2 S) and Lawesson's reagent reduced leukocyte infiltration and adherence to the vascular endothelium via glibenclamide-inhibitable K ATP channels, and the CSE inhibitor BCA promoted leukocyte infiltration.…”

Hydrogen Sulfide Is an Endogenous Potentiator of T Cell Activation

“…3), metabolic hibernation (4,5), protection from ischemia/reperfusion injury (6 -10), oxygen sensing (11), vasodilatation (12,13), and promotion of angiogenesis (14). In common with nitric oxide, H 2 S is also implicated as both a pro- (15)(16)(17)(18) and antiinflammatory (18 -21) molecule in innate immune cells. Although the role of H 2 S signaling has been characterized in many other tissues and systems, it is unclear what role it plays in the regulation of the adaptive immune system.…”