atb-346 and Cardiovascular-Diseases

Shortly after the discovery of the role of hydrogen sulfide (H. There remains a need to better understand the underlying mechanisms for some of the observed effects of H. The proof-of-concept clinical studies reviewed herein pave the way for examination, in a clinical setting, of several other potential applications of H

Topics: Animals; Arthritis; Captopril; Cardiovascular Agents; Cardiovascular Diseases; Dose-Response Relationship, Drug; Humans; Hydrogen Sulfide; Naproxen

Hydrogen sulfide is an endogenous gaseous mediator that plays important roles in many physiological processes in microbes, plants, and animals. This chapter focuses on the important roles of hydrogen sulfide in protecting tissues against injury, promoting the repair of damage, and downregulating the inflammatory responses. The chapter focuses largely, but not exclusively, on these roles of hydrogen sulfide in the gastrointestinal tract. Hydrogen sulfide is produced throughout the gastrointestinal tract, and it contributes to maintenance of mucosal integrity. Suppression of hydrogen sulfide synthesis renders the tissue more susceptible to injury and it impairs repair. In contrast, administration of hydrogen sulfide donors can increase resistance to injury and accelerate repair. Hydrogen sulfide synthesis is rapidly and dramatically enhanced in the gastrointestinal tract after injury is induced. These increases occur specifically at the site of tissue injury. Hydrogen sulfide also plays an important role in promoting resolution of inflammation, and restoration of normal tissue function. In recent years, these beneficial actions of hydrogen sulfide have provided the basis for development of novel hydrogen sulfide-releasing drugs. Nonsteroidal anti-inflammatory drugs that release small amounts of hydrogen sulfide are among the most advanced of the hydrogen sulfide-based drugs. Unlike the parent drugs, these modified drugs do not cause injury in the gastrointestinal tract, and do not interfere with healing of preexisting damage. Because of the increased safety profile of these drugs, they can be used in circumstances in which the toxicity of the parent drug would normally limit their use, such as in chemoprevention of cancer.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Cystathionine beta-Synthase; Cystathionine gamma-Lyase; Gastrointestinal Tract; Gene Expression Regulation; Humans; Hydrogen Sulfide; Inflammation; Inflammatory Bowel Diseases; Intestinal Mucosa; Naproxen; Neurodegenerative Diseases; Pain; Protective Agents; Signal Transduction; Spinal Cord Injuries