A timeline of hydrogen sulfide (H2S) research: From environmental toxin to biological mediator

Abstract

The history of HS - as an environmental toxin - dates back to 1700, to the observations of the Italian physician Bernardino Ramazzini, whose book "De Morbis Artificum Diatriba" described the painful eye irritation and inflammation of "sewer gas" in sewer workers. The gas has subsequently been identified as hydrogen sulfide (HS), and opened three centuries of research into the biological roles of HS. The current article highlights the key discoveries in the field of HS research, including (a) the toxicological studies, which characterized HS as an environmental toxin, and identified some of its modes of action, including the inhibition of mitochondrial respiration; (b) work in the field of bacteriology, which, starting in the early 1900s, identified HS as a bacterial product - with subsequently defined roles in the regulation of periodontal disease (oral bacterial flora), intestinal epithelial cell function (enteral bacterial flora) as well as in the regulation of bacterial resistance to antibiotics; and (c), work in diverse fields of mammalian biology, which, starting in the 1940s, identified HS as an endogenous mammalian enzymatic product, the functions of which - among others, in the cardiovascular and nervous system - have become subjects of intensive investigation for the last decade. The current review not only enumerates the key discoveries related to HS made over the last three centuries, but also compiles the most frequently cited papers in the field which have been published over the last decade and highlights some of the current 'hot topics' in the field of HS biology.

Neuroprotective effects of ammonium tetrathiomolybdate, a slow-release sulfide donor, in a rodent model of regional stroke

“…Basic sulfur salts, the so-called sulfide generators, showed initial promise as putative therapies [15], with efficacy demonstrated in several preclinical ischemia/reperfusion rodent models [17][18][19]. However, upon dissolution, these basic salts release all of their sulfur as sulfide in a near-instantaneous fashion with resulting implications for safety and efficacy [40].…”

Intake of red and processed meat, use of non-steroid anti-inflammatory drugs, genetic variants and risk of colorectal cancer; a prospective study of the Danish “Diet, Cancer and Health” cohort

“…6 Risk estimate for the increment of 10 g dietary fibers per day. 7 Risk estimate for the increment of 25 g red and processed meat per day. 8 Risk estimate for the increment of 1 kJ energy per day (incl alcohol).…”

“…Epidemiological studies suggest that high intake of red and particularly processed meat may increase the CRC risk [3], whereas long-term use of non-steroid anti-inflammatory drugs (NSAIDs) including aspirin (acetylic acid) may reduce the risk of CRC [4,5]. Investigations on the potential carcinogenic mechanisms of red and processed meat have suggested that meat may confer carcinogenesis by being a source of cooking mutations (heterocyclic amine, N-nitroso compounds) formed during preparation [6], organic sulfur-containing proteins leading to a high content of H 2 S in the intestinal lumen, a highly potent regulator of intestinal cell function including inflammation and cell death signaling [7] and/or microbial factors arising during storage [8]. Similarly, the underlying cancer protective mechanisms of NSAID have been investigated and both COX-2 dependent and COX-2 independent mechanisms have been suggested [9,10].…”

Diallyl trisulfide, a H2S donor, inhibits cell growth of human papillary thyroid carcinoma KTC‐1 cells through a positive feedback loop between H2S and cystathionine‐gamma‐lyase

“…H 2 S, previously regarded primarily as an environmental hazard and toxic gas, has recently been recognized as the third gasotransmitter after carbon monoxide (CO) and nitric oxide (NO; Szabo, ). H 2 S has become a focus of researches because of its role in various biological processes, such as neuronal health (Paul & Snyder, ), cardiovascular health, immune response (Yuan, Shen, & Kevil, ), and inflammation (Luo et al, ).…”