Hydrogen sulfide-based therapeutics and gastrointestinal diseases: translating physiology to treatments.

摘要

Hydrogen sulfide (H_2S) is a gaseous meditator that has various physiological and pathophysiological roles in the body. It has been shown to be an important mediator of gastrointestinal (GI) mucosal defense and contributes significantly to repair of damage and resolution of inflammation. Synthesis of H_2S increases markedly after mucosal injury, and inhibition of H_2S in such circumstances leads to delayed healing and exacerbated inflammation. The beneficial effects of H_2S may be attributable to its ability to elevate mucosal blood flow, prevent leukocyte-endothelial adhesion, reduce oxidative stress, and stimulate angiogenesis. The use of H_2S-donating agents and inhibitors of the key enzymes contributing to H_2S synthesis have provided strong evidence for the importance of H_2S in enhancing mucosal resistance to damage, as well as modulating inflammation and repair. In recent years, significant evidence has been generated to support the notion that these positive aspects of H_2S can be exploited in drug design, particularly for arthritis, inflammatory bowel disease, and colon cancer chemoprevention. Thus novel H_2S-based therapies have been shown to be effective anti-inflammatories that can promote the resolution of inflammation and accelerate the healing of GI ulcers. Encouraging results have already been seen experimentally with a mesalamine derivative and with H_2S-releasing derivatives of nonsteroidal anti-inflammatory drugs.