Role of Hydrogen Sulfide in the Pathology of Inflammation

Madhav Bhatia

doi:10.6064/2012/159680

Abstract

Hydrogen sulfide (H2S) is a well-known toxic gas that is synthesized in the human body from the amino acids cystathionine, homocysteine, and cysteine by the action of at least two distinct enzymes: cystathionine-γ-lyase and cystathionine-β-synthase. In the past few years, H2S has emerged as a novel and increasingly important biological mediator. Imbalances in H2S have also been shown to be associated with various disease conditions. However, defining the precise pathophysiology of H2S is proving to be a complex challenge. Recent research in our laboratory has shown H2S as a novel mediator of inflammation and work in several groups worldwide is currently focused on determining the role of H2S in inflammation. H2S has been implicated in different inflammatory conditions, such as acute pancreatitis, sepsis, joint inflammation, and chronic obstructive pulmonary disease (COPD). Active research on the role of H2S in inflammation will unravel the pathophysiology of its actions in inflammatory conditions and may help develop novel therapeutic approaches for several, as yet incurable, disease conditions.

Highlights

Hydrogen sul de (H2S) is a colorless, ammable, watersoluble gas characterized by a peculiar smell of rotten eggs. e toxic effects of H2S have been known for more than 300 years, and it has long been believed to be just an environmental pollutant [1]
We have shown that PPTA de ciency and blockage of H2S synthesis may play an important role that can regulate the toll-like receptor 4 (TLR4) pathway and subsequent innate immune response in acute pancreatitis, implying an interaction between SP/H2S occurs via TLR4 and nuclear factor- (NF-)kB pathway
In a more recent study [70], we have shown that H2S regulates in ammatory response by activating the extracellular signal related kinase (ERK) pathway in polymicrobial sepsis

Summary

Introduction

Hydrogen sul de (H2S) is a colorless, ammable, watersoluble gas characterized by a peculiar smell of rotten eggs. e toxic effects of H2S have been known for more than 300 years, and it has long been believed to be just an environmental pollutant [1]. Cystathionine-ββ-synthase (CBS) in the central nervous system and cystathionine-γγ-lyase (CSE) in the cardiovascular system are the key enzymes mostly responsible for the endogenous generation of H2S. The mitochondrial oxidation mechanism represents the most important route of H2S catabolism It involves several enzymatic steps catalyzed by quinine oxidoreductase, S-dioxygenase, and S-transferase and, overall, leads to the formation of thiosulfate. H2S is an endogenous reducing agent which can be consumed by a variety of circulating oxidant species in the vasculature such as peroxynitrite, hypochlorite, superoxide, or hydrogen peroxide [16,17,18,19] It is excreted mainly by the kidney as free or conjugated sulfate [13]. Recent work in our laboratory and others has shown a key role of H2S as a mediator of in ammation in different clinical conditions

Acute Pancreatitis and Associated Lung Injury

Sepsis

Burn Injuries

Findings

The Way Forward