Hydrogen sulphide (H2S) is increasingly being recognized as an important signalling molecule in the cardiovascular and nervous systems. The production of H2S from L-cysteine is catalysed primarily by two enzymes, cystathionine gamma-lyase and cystathionine beta-synthase. Evidence is accumulating to demonstrate that inhibitors of H2S production or therapeutic H2S donor compounds exert significant effects in various animal models of inflammation, reperfusion injury and circulatory shock. H2S can also induce a reversible state of hypothermia and suspended-animation-like state in rodents. This article overviews the physiology and biochemistry of H2S, summarizes the effects of H2S inhibitors or H2S donors in animal models of disease and outlines the potential options for the therapeutic exploitation of H2S.

Hydrogen sulphide and its therapeutic potential

Rural Industries Research and Development Corporation

The information available on the biological activity of hydrogen sulfide has been examined for present status of critical results pertaining to the toxicity of hydrogen sulfide. This review of the literature is intended as an evaluative report rather than an annotated bibliography of all the source material examined on hydrogen sulfide. The information was selected as it might relate to potential toxic effects of hydrogen sulfide to man and summarized, noting information gaps that may require further investigation. Several recommendations are listed for possible consideration for either toxicological research or additional short- and long-term tests. Two bibliographies have been provided to assist in locating references considered in this report: (1) literature examined but not cited and (2) reference citations. The majority of the references in the first bibliography were considered peripheral information and less appropriate for inclusion in this report.

A Critical Review of the Literature on Hydrogen Sulfide Toxicity

Efforts to understand human physiology through the study of champion athletes and record performances have been ongoing for about a century. For endurance sports three main factors – maximal oxygen consumption , the so-called ‘lactate threshold’ and efficiency (i.e. the oxygen cost to generate a give running speed or cycling power output) – appear to play key roles in endurance performance. and lactate threshold interact to determine the ‘performance ‘ which is the oxygen consumption that can be sustained for a given period of time. Efficiency interacts with the performance to establish the speed or power that can be generated at this oxygen consumption. This review focuses on what is currently known about how these factors interact, their utility as predictors of elite performance, and areas where there is relatively less information to guide current thinking. In this context, definitive ideas about the physiological determinants of running and cycling efficiency is relatively lacking in comparison with and the lactate threshold, and there is surprisingly limited and clear information about the genetic factors that might pre-dispose for elite performance. It should also be cautioned that complex motivational and sociological factors also play important roles in who does or does not become a champion and these factors go far beyond simple physiological explanations. Therefore, the performance of elite athletes is likely to defy the types of easy explanations sought by scientific reductionism and remain an important puzzle for those interested in physiological integration well into the future.

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Endurance exercise performance: the physiology of champions

Reactive oxygen, nitrogen, and sulfur species, referred to as ROS, RNS, and RSS, respectively, are produced during normal cell function and in response to various stimuli. An imbalance in the metabolism of these reactive intermediates results in the phenomenon known as oxidative stress. If left unchecked, oxidative molecules can inflict damage on all classes of biological macromolecules and eventually lead to cell death. Indeed, sustained elevated levels of reactive species have been implicated in the etiology (e.g., atherosclerosis, hypertension, diabetes) or the progression (e.g., stroke, cancer, and neurodegenerative disorders) of a number of human diseases.1 Over the past several decades, however, a new paradigm has emerged in which the aforementioned species have also been shown to function as targeted, intracellular second messengers with regulatory roles in an array of physiological processes.2 Against this backdrop, it is not surprising that considerable ongoing efforts are aimed at elucidating the role that these reactive intermediates play in health and disease.

Site-specific, covalent modification of proteins represents a prominent molecular mechanism for transforming an oxidant signal into a biological response. Amino acids that are candidates for reversible modification include cysteines whose thiol (i.e., sulfhydryl) side chain is deprotonated at physiological pH, which is an important attribute for enhancing reactivity. While reactive species can modify other amino acids (e.g., histidine, methionine, tryptophan, and tyrosine), this Review will focus exclusively on cysteine, whose identity as cellular target or “sensor” of reactive intermediates is most prevalent and established.3 Oxidation of thiols results in a range of sulfur-containing products, not just disulfide bridges, as typically presented in biochemistry textbooks. An overview of the most relevant forms of oxidized sulfur species found in vivo is presented in Chart 1.






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Chart 1

Biologically Relevant Cysteine Chemotypesa

aRed, irreversible modifications. Green, unique enzyme intermediates. Note: Additional modifications can form as enzyme intermediates including thiyl radicals, disulfides, and persulfides.

Cysteine-Mediated Redox Signaling: Chemistry, Biology, and Tools for Discovery

Arterial hypoxemia has been reported in horses during heavy exercise, but its mechanism has not been determined. With the use of the multiple inert gas elimination technique, we studied five horses...

Mechanism of exercise-induced hypoxemia in horses

Recent studies using microspheres in dogs, pigs and goats have demonstrated considerable heterogeneity of pulmonary perfusion within isogravitational planes. These studies demonstrate a minimal rol...

Pulmonary blood flow distribution in standing horses is not dominated by gravity

Relationship of structure and function of the avian respiratory system to disease susceptibility

Exercise-induced pulmonary haemorrhage (EIPH) causes serious economic losses in the horse racing industry. Endoscopic examination indicates that 40-90% of horses exhibit EIPH following sprint exercise, but the limitations of the endoscope prevent diagnosis in many horses. Bronchoalveolar lavage (BAL) was utilised to detect red blood cells (RBCs) in the terminal airways in 6 horses. Two lavages were performed at weekly intervals prior to exercise, one within 90 min after exercise, and 5 at weekly intervals after exercise. The horses were exercised strenuously at 12.5-14.6 m/s on a treadmill (3 degree incline). Heart rates ranged from 192-207 beats/min, and mean pulmonary arterial pressures (mPAP) ranged from 80-102 mmHg. Neither epistaxis nor endoscopic evidence of EIPH was seen in any of the 6 horses following exercise. However, the number of RBCs in the lavage fluid increased significantly over control values immediately after exercise in all horses but returned to control values by one week after exercise. Haemosiderophages in the BAL fluid did not increase until one week after exercise and remained elevated for 3 weeks after exercise. Twenty per cent of the total population of alveolar macrophages contained haemosiderin. A positive relationship occurred between the number of RBCs in the lavage fluid and mPAP; the amount of haemorrhage increased as the mPAP exceeded 80 to 90 mmHg. The results with BAL used as the diagnostic tool, suggest that all strenuously exercised horses may exhibit EIPH; the amount of haemorrhage appears to be associated with the magnitude of the high pulmonary arterial pressure.

Quantification of exercise‐induced pulmonary haemorrhage with bronchoalveolar lavage

We determined the spatial distribution of pulmonary blood flow at rest and during increasing levels of exercise (34, 59, and 90% of maximal oxygen consumption) in Thoroughbred racehorses (n = 4) us...

M. R. Fedde

Papers

Mechanism of exercise-induced hypoxemia in horses

Pulmonary blood flow distribution in standing horses is not dominated by gravity

Relationship of structure and function of the avian respiratory system to disease susceptibility

Quantification of exercise‐induced pulmonary haemorrhage with bronchoalveolar lavage

Minimal redistribution of pulmonary blood flow with exercise in racehorses.