Diet and Hydrogen Sulfide Production in Mammals.

In recent times, it has emerged that some dietary sulfur compounds can act on mammalian cell signaling systems their propensity to release hydrogen sulfide (HS). HS plays important biochemical and physiological roles in the heart, gastrointestinal tract, brain, kidney, and immune systems of mammals. Reduced levels of HS in cells and tissues correlate with a spectrum of pathophysiological conditions, including heart disease, diabetes, obesity, and altered immune function.

Lifespan and healthspan benefits of exogenous HS in are independent from effects downstream of mutation.

Caloric restriction (CR) is one of the most effective interventions to prolong lifespan and promote health. Recently, it has been suggested that hydrogen sulfide (HS) may play a pivotal role in mediating some of these CR-associated benefits. While toxic at high concentrations, HS at lower concentrations can be biologically advantageous.

An Appraisal of Developments in Allium Sulfur Chemistry: Expanding the Pharmacopeia of Garlic.

Alliums and allied plant species are rich sources of sulfur compounds that have effects on vascular homeostasis and the control of metabolic systems linked to nutrient metabolism in mammals. In view of the multiple biological effects ascribed to these sulfur molecules, researchers are now using these compounds as inspiration for the synthesis and development of novel sulfur-based therapeutics. This research has led to the chemical synthesis and biological assessment of a diverse array of sulfur compounds representative of derivatives of -alkenyl-l-cysteine sulfoxides, thiosulfinates, ajoene molecules, sulfides, and -allylcysteine.

Garlic and Gaseous Mediators.

Garlic (Allium sativum) and allied plant species are rich sources of sulfur compounds. Major roles for garlic and its sulfur constituents include the regulation of vascular homeostasis and the control of metabolic systems linked to nutrient metabolism. Recent studies have indicated that some of these sulfur compounds, such as diallyl trisulfide (DATS), alter the levels of gaseous signalling molecules including nitric oxide (NO), hydrogen sulfide (HS), and perhaps carbon monoxide (CO) in mammalian tissues.

Is there a role of HS in mediating health span benefits of caloric restriction?

Caloric restriction (CR) is a dietary regimen that aims to reduce the intake of total calories while maintaining adequate supply of key nutrients so as to avoid malnutrition. CR is one of only a small number of interventions that show promising outcomes on health span and lifespan across different species. There is growing interest in the development of compounds that might replicate CR-related benefits without actually restricting food intake.

A novel slow-releasing hydrogen sulfide donor, FW1256, exerts anti-inflammatory effects in mouse macrophages and in vivo.

Exogenous hydrogen sulfide (HS) is known to exert anti-inflammatory effects both in macrophages and in animal models. In this study, we first showed that NaHS caused a concentration dependent reduction in TNFα and IL-6 secretion in LPS-stimulated RAW264.7 macrophages in the absence of cell death.

Energy crisis precedes global metabolic failure in a novel Caenorhabditis elegans Alzheimer Disease model.

Alzheimer Disease (AD) is a progressive neurological disorder characterized by the deposition of amyloid beta (Aβ), predominantly the Aβ form, in the brain. Mitochondrial dysfunction and impaired energy metabolism are important components of AD pathogenesis. However, the causal and temporal relationships between them and AD pathology remain unclear.

H2S Synthesizing Enzymes: Biochemistry and Molecular Aspects.

Hydrogen sulfide (H2S) is a biologically active gas that is synthesized naturally by three enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthetase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST). These enzymes are constitutively present in a wide array of biological cells and tissues and their expression can be induced by a number of disease states. It is becoming increasingly clear that H2S is an important mediator of a wide range of cell functions in health and in disease.

Hydrogen sulfide promotes adipogenesis in 3T3L1 cells.

The effect of hydrogen sulfide (H2S) on differentiation of 3T3L1-derived adipocytes was examined. Endogenous H2S was increased after 3T3L1 differentiation. The expression of the H2S-synthesising enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (3-MST), was increased in a time-dependent manner during 3T3L1 differentiation.

The slow-releasing hydrogen sulfide donor, GYY4137, exhibits novel anti-cancer effects in vitro and in vivo.

The slow-releasing hydrogen sulfide (H₂S) donor, GYY4137, caused concentration-dependent killing of seven different human cancer cell lines (HeLa, HCT-116, Hep G2, HL-60, MCF-7, MV4-11 and U2OS) but did not affect survival of normal human lung fibroblasts (IMR90, WI-38) as determined by trypan blue exclusion. Sodium hydrosulfide (NaHS) was less potent and not active in all cell lines. A structural analogue of GYY4137 (ZYJ1122) lacking sulfur and thence not able to release H₂S was inactive.

Hydrogen sulfide: regulatory role on blood pressure in hyperhomocysteinemia.

Hyperhomocysteinemia (HHcy) is a metabolic disorder marked by an excess amount of the amino acid homocysteine (Hcy) in the blood stream. Hcy is a H(2)S precursor-formed from the metabolism of methionine. Elevated Hcy levels have been associated with higher blood pressure.

Effect of S-diclofenac, a novel hydrogen sulfide releasing derivative inhibit rat vascular smooth muscle cell proliferation.

S-diclofenac (2-[(2,6-dichlorophenyl) amino] benzene acetic acid 4-(3H-1,2,dithiol-3-thione-5-yl) phenyl ester) is a novel molecule comprising a hydrogen sulfide (H2S)-releasing dithiol-thione moiety attached by an ester linkage to diclofenac. Effect of S-diclofenac (H2S donor) on cell proliferation was investigated on the primary and immortalized rat aortic vascular smooth muscle cells (SMC). Smooth muscle cell proliferation has been considered as a key event in vascular injury in diseases such as atherosclerosis and restenosis after invasive intervention.

The novel proangiogenic effect of hydrogen sulfide is dependent on Akt phosphorylation.

Objective: Hydrogen sulfide (H(2)S) has been reported to be a gasotransmitter which regulates cardiovascular homeostasis. The present study aims to examine the hypothesis that hydrogen sulfide is able to promote angiogenesis.

Methods: Angiogenesis was assessed using in vitro parameters (i.

Chronic sodium hydrosulfide treatment decreases medial thickening of intramyocardial coronary arterioles, interstitial fibrosis, and ROS production in spontaneously hypertensive rats.

Hydrogen sulfide (H(2)S) is a gasotransmitter that regulates cardiovascular functions. The present study aimed to examine the hypothesis that chronic treatment with sodium hydrosulfide (NaHS, an H(2)S donor) is able to prevent left-ventricular remodeling in spontaneously hypertensive rats (SHR). Four-week-old SHR were treated with NaHS (10, 30, and 90 micromol x kg(-1) x day(-1)), a combination of NaHS (30 micromol x kg(-1) x day(-1)) and glibenclamide (5 mg x kg(-1) x day(-1)), glibenclamide alone (5 mg x kg(-1) x day(-1)), hydralazine alone (10 mg x kg(-1) x day(-1)), and placebo for 3 mo.

Endogenous hydrogen sulfide regulates leukocyte trafficking in cecal ligation and puncture-induced sepsis.

Hydrogen sulfide (H(2)S) is recognized increasingly as a proinflammatory mediator in various inflammatory conditions. Here, we have investigated the role of H(2)S in regulating expression of some endothelial adhesion molecules and recruitment of leukocytes to inflamed sites in sepsis. Male Swiss mice were subjected to cecal ligation and puncture (CLP)-induced sepsis and treated with saline (i.

Anti-inflammatory and gastrointestinal effects of a novel diclofenac derivative.

S-diclofenac (2-[(2,6-dichlorophenyl)amino]benzeneacetic acid 4-(3H-1,2,dithiol-3-thione-5-yl)phenyl ester; ACS 15) is a novel molecule comprising a hydrogen sulfide (H2S)-releasing dithiol-thione moiety attached by an ester linkage to diclofenac. S-diclofenac administration inhibited lipopolysaccharide-induced inflammation (as evidenced by reduced lung and liver myeloperoxidase activity) and caused significantly less gastric toxicity than diclofenac. S-diclofenac did not affect blood pressure or heart rate of the anesthetized rat.

Hydrogen sulfide-induces DNA damage and changes in apoptotic gene expression in human lung fibroblast cells.

Hydrogen sulfide (H2S) has been shown previously to exert proapoptotic activity. However, the mechanism(s) by which H2S affects cell growth and function have not been addressed adequately. In this study, cultured human lung fibroblasts were treated with the H2S donor NaHS (10-75 microM; 12-48 h).

The role of urotensin II in cardiovascular and renal physiology and diseases.

Urotensin II (U-II) is a cyclic neuropeptide that was first isolated from teleost fish some 35 years ago. Mammalian U-II is a powerful vasoconstrictor with a potency greater than that of endothelin-1.Nevertheless, unlike endothelin-1, which constricts all or nearly all vascular beds, the vasoactive effects of U-II are reported to be dependent both on the species and on the regional vascular bed examined.

Endogenous hydrogen sulfide contributes to the cardioprotection by metabolic inhibition preconditioning in the rat ventricular myocytes.

The possible role of hydrogen sulfide (H2S) in cardioprotection was investigated in isolated rat ventricular myocytes exposed to severe metabolic inhibition (MI) in glucose-free buffer containing 2-deoxy-D-glucose (2-DOG), an inhibitor of glycolysis. Pretreatment (30 min) with NaHS (a H2S donor) at concentrations of 10(-5) to 10(-4) mol/L caused a concentration related increase in cell viability and the ratio of rod-shaped cells. A time course study showed that NaHS-induced cardioprotection occurred in 2 time windows (approximately 1 h and 16-28 h).

Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes.

Endogenous H(2)S is synthesized mainly by cystathionine gamma-lyase in the heart. The present study investigated the role of H(2)S in cardioprotection induced by ischemic preconditioning. We have examined the effect of endogenous H(2)S and exogenous application of NaHS (H(2)S donor) on cardiac rhythm in the isolated rat heart subjected to low-flow ischemia insults as well as cell viability and function in isolated myocytes exposed to simulated ischemia solution.