Hydrogen sulphide induces mouse paw oedema through activation of phospholipase A2

Background and purpose: Hydrogen sulphide (H2S), considered as a novel gas transmitter, is produced endogenously in mammalian tissue from L-cysteine by two enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). Recently, it has been reported that H2S contributes to the local and systemic inflammation in several experimental animal models. We conducted this study to investigate on the signaling involved in H2S induced inflammation. Experimental approach: L-cysteine or sodium hydrogen sulphide (NaHS) were injected in the mouse hind paw and oedema formation was evaluated for 60 min. In order to investigate on the H2S–induced oedema formation, we used different pharmacological tools: serotonin and histamine receptor antagonists, KATP channels or arachidonic acid cascade inhibitors. Prostaglandin levels were determined in hind paw exudates by radioimmunoassay. Finally, the histological analysis was performed on L-cisteine injected hind paw. Key results: Both NaHS and L-cysteine caused oedema formation characterized by a fast onset which peaked at 30 minutes. This oedematogenic action was not associated with histamine, serotonin release or KATP channel activation. Conversely, the oedema formation was significantly inhibited by ciclooxygenase and phospholipase A2 selective inhibitors. Moreover, the prostaglandin levels were significantly increased in exudates of hind paw injected with NaHS or L-cysteine. The histological study clearly showed an inflammatory state with a loss of tissue organization. Conclusion and implication: We could assume that the phospholipase A2 and prostaglandins production are involved in H2S pro-inflammatory effect in the mouse hind paw. The present study could contribute to understand the role of L-cysteine/H2S pathway in inflammatory disease