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* Note that these authors are not affiliated with Antibe Therapeutics.
Paclitaxel-induced neuropathic pain (PINP) is a dose-limiting side effect that largely affects the patient’s quality of life and may limit the use of the drug as a chemotherapeutic agent for treating metastatic breast cancer and other solid tumors. Recently, a putative role for the gaseous mediator hydrogen sulfide (H2S) in nociception modulation has been suggested. The aim of the present study was to investigate the potential efficacy of a slow release H2S donor to alleviate and prevent PINP. The H2S donor enhanced paclitaxel’s anti-proliferative effects against the breast cancer cell line MCF-7, suggesting that it alleviates paclitaxel-induced thermal hyperalgesia, via KATP channels. It also prevents PINP possibly by blocking the paclitaxel-induced reduction in the generation of H2S, in the tissues, while enhancing the anti-cancer activity of paclitaxel.
The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H2S) were recently demonstrated in the context of different inflammatory diseases. In particular, H2S is able to suppress the production of pro-inflammatory mediators by lymphocytes and innate immunity cells. Considering these biological effects of H2S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H2S, more evidence is needed to understand the pathophysiology and the potential of H2S as a therapeutic agent. This is an overview on H2S biological effects, on its role in immune-mediated inflammatory diseases, on H2S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.
NSAIDs cause damage in the small intestine in a bacteria-dependent manner. As high-fat diet (HFD) is a potent inducer of gut dysbiosis, we investigated the effects of HFD on bacterial flora in the small intestine and NSAID-induced enteropathy. HFD-fed mice exhibited increased susceptibility to NSAID-induced damage in the small intestine; this phenotype was observed in normal diet-fed mice that received small intestinal microbiota from HFD-fed mice. Administration of neutralizing antibodies to HFD-fed mice reduced intestinal permeability and prevented exacerbation of NSAID-induced damage. Thus, HFD-induced microbial dysbiosis in small intestine caused microinflammation and increase in intestinal permeability, resulting in the aggravation of NSAID-induced small intestinal damage.
The authors identify that H2S has a protective role in paramyxovirus infection by modulating inflammatory responses and viral replication. In this study, they tested the antiviral and anti-inflammatory activity of an H2S donor on enveloped RNA viruses from Ortho-, Filo-, Flavi- and Bunyavirus families, for which there is no FDA-approved vaccine or therapeutic available, with the exception of influenza. They found that this approach significantly reduced replication of all tested viruses. In a model of influenza infection, this treatment was associated with decreased expression of viral proteins and mRNA, suggesting inhibition of an early step of replication. The antiviral activity coincided with the decrease of viral-induced pro-inflammatory mediators and viral-induced nuclear translocation of transcription factors from Nuclear Factor (NF)-kB and Interferon Regulatory Factor families. In conclusion, increasing cellular H2S is associated with significant antiviral activity against a broad range of emerging enveloped RNA viruses, and should be further explored as potential therapeutic approach in relevant pre-clinical models of viral infections.
The chemical versatility of sulfur and its abundance in the prebiotic Earth as reduced sulfide (H2S) implicate this molecule in the origin of life 3.8 billion years ago and also as a major source of energy in the first seven-eighths of evolution. This article provides an in-depth review of the origins of hydrogen sulfide’s physiological functions, also explaining its unique role as a signalling molecule and metabolic regulator, including its anti-inflammatory properties.
Hydrogen sulfide (H2S) is a unique gasotransmitter, with regulatory roles in the cardiovascular, nervous, and immune systems. Some of the vascular actions of H2S (stimulation of angiogenesis, relaxation of vascular smooth muscle) resemble those of nitric oxide (NO). Although it was generally assumed that H2S and NO exert their effects via separate pathways, the results of the current study show that H2S and NO are mutually required to elicit angiogenesis and vasodilatation.
Hydrogen sulfide (H2S) is a gaseous mediator synthesized from cysteine by cystathionine ? lyase (CSE) and other naturally occurring enzymes. Pharmacological experiments using H2S donors and genetic experiments using CSE knockout mice suggest important roles for this vasodilator gas in the regulation of blood vessel caliber, cardiac response to ischemia/reperfusion injury, and inflammation.
In vascular tissues, hydrogen sulphide (H2S) is mainly produced from L-cysteine by the cystathionine gamma-lyase (CSE) enzyme. Recent studies show that administration of H2S to endothelial cells in culture stimulates cell proliferation, migration and tube formation. Angiogenesis, the formation of new blood vessels, is crucial in the early stage of wound healing. Pharmacological modulation of H2S-mediated angiogenic pathways may open the door for novel therapeutic approaches.
The recent discovery that hydrogen sulfide (H2S) is an endogenously produced gaseous second messenger capable of modulating many physiological processes, much like nitric oxide, prompted us to investigate the potential of H2S as a cardioprotective agent. In the current study, we demonstrate that H2S may be of value in cytoprotection during the evolution of myocardial infarction and that either administration of H2S or the modulation of endogenous production may be of clinical benefit in ischemic disorders.
H2S is an important gasotransmitter, generated in mammalian cells from L-cysteine metabolism. As it stimulates KATP channels in vascular smooth muscle cells, H2S may also function as an endogenous opener of KATP channels in INS-1E cells, an insulin-secreting cell line. Interaction among H2S, glucose and the KATP channel may constitute an important and novel mechanism for the fine control of insulin secretion from pancreatic ?-cells.
The endogenous metabolism and physiological functions of hydrogen sulfide (H2S) position this gas well in the novel family of endogenous gaseous transmitters, termed “gasotransmitters.” This positioning of H2S will open an exciting field—H2S physiology—encompassing realization of the interaction of H2S and other gasotransmitters, sulfurating modification of proteins, and the functional role of H2S in multiple systems. It may shed light on the pathogenesis of many diseases related to the abnormal metabolism of H2S.
An abundance of experimental evidence suggests that hydrogen sulfide (H2S) plays a prominent role in physiology and pathophysiology. Many targets exist for H2S therapy. The molecular targets of H2S include proteins, enzymes, transcription factors, and membrane ion channels. Novel H2S precursors are being synthesized and discovered that are capable of releasing H2S in a slow and sustained manner. This presents a novel and advantageous approach to H2S therapy for treatment of chronic conditions associated with a decline in endogenous H2S, such as diabetes and cardiovascular disease.
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