Background and purpose:  Recent findings suggest that the noxious gas H₂S is produced endogenously, and that physiological concentrations of H₂S are able to modulate pain and inflammation in rodents. This study was undertaken to evaluate the ability of endogenous and exogenous H₂S to modulate carrageenan‐induced synovitis in the rat knee.Experimental approach:  Synovitis was induced in Wistar rats by intra‐articular injection of carrageenan into the knee joint. Sixty minutes prior to carrageenan injection, the rats were pretreated with indomethacin, an inhibitor of H₂S formation (dl‐propargylglycine) or an H₂S donor [Lawesson's reagent (LR)].Key results:  Injection of carrageenan evoked knee inflammation, pain as characterized by impaired gait, secondary tactile allodynia of the ipsilateral hindpaw, joint swelling, histological changes, inflammatory cell infiltration, increased synovial myeloperoxidase, protein nitrotyrosine residues, inducible NOS (iNOS) activity and NO production. Pretreatment with LR or indomethacin significantly attenuated the pain responses, and all the inflammatory and biochemical changes, except for the increased iNOS activity, NO production and 3‐NT. Propargylglycine pretreatment potentiated synovial iNOS activity (and NO production), and enhanced macrophage infiltration, but had no effect on other inflammatory parameters.Conclusions and implications:  Whereas exogenous H₂S delivered to the knee joint can produce a significant anti‐inflammatory and anti‐nociceptive effect, locally produced H₂S exerts little immunomodulatory effect. These data further support the development and use of H₂S donors as potential alternatives (or complementary therapies) to the available anti‐inflammatory compounds used for treatment of joint inflammation or relief of its symptoms.

Background: Inflammatory stimuli activate inducible nitric oxide synthase (iNOS) in a variety of cell types, including osteoclasts (OC) and osteoblasts, resulting in sustained NO production. In this study, we evaluate the alveolar bone loss in rats with periodontitis under long‐term iNOS inhibition, and the differentiation and activity of OC from iNOS‐knockout (KO) mice in vitro.Methods: Oral aminoguanidine (an iNOS inhibitor) or water treatment was started 2 weeks before induction of periodontitis. Rats were sacrificed 3, 7, or 14 days after ligature placement, and alveolar bone loss was evaluated. In vitro OC culture experiments were also performed to study the differentiation of freshly isolated bone marrow cells from both iNOS KO and wild‐type C57BL/6 mice. OC were counted 6 days later after tartrate‐resistant acid phosphatase staining (a marker of osteoclast identity), and bone resorption activity was assessed by counting the number of resorption pits on dentin disks.Results: Rats with ligature showed progressive and significant alveolar bone loss compared to sham animals, and aminoguanidine treatment significantly inhibited ligature‐induced bone loss at 7 and 14 days after the induction. In comparison to bone marrow cells from wild‐type mice, cells from iNOS KO mice showed decreased OC growth and the resulting OC covered a smaller culture dish area and generated fewer resorption pit counts.Conclusion: Our results demonstrate that iNOS inhibition prevents alveolar bone loss in a rat model of ligature‐induced periodontitis, thus confirming that iNOS‐derived NO plays a crucial role in the pathogenesis of periodontitis, probably by stimulating OC differentiation and activity.

Skin diseases constitute a major health problem affecting a high proportion of the population every day and have different aetiologies that include inflammation, infections, and tumours. Hydrogen sulfide (H₂S) is a gaseous signalling molecule recognized as a gasotransmitter together with NO and carbon monoxide. Under physiological conditions, H₂S is produced in the skin by enzymic pathways and plays a physiological role in a variety of functions, such as vasodilatation, cell proliferation, apoptosis, and inflammation. Alterations of H₂S production are implicated in a variety of dermatological diseases, such as psoriasis, melanoma, and other dermatoses. On the other hand, H₂S‐releasing‐based therapies based on H₂S donor compounds are being developed to treat some of these situations. In this review, we provide an up‐to‐date overview of the role of H₂S in the normal skin and its clinical and pathological significance, as well as the therapeutic potential of different H₂S donors for treatment of skin diseases.Linked Articles: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc