La dieta como fuente de sulfuro de hidrógeno y sus efectos en la salud y la enfermedad / Diet as a source of hydrogen sulfide and its effects on health and disease

Conocido originalmente por sus efectos deletéreos en la salud, recientemente se ha reconocido al sulfuro de hidrógeno (H2S) como un gasotransmisor de importancia biológica, al igual que el óxido nítrico y el monóxido de carbono. El H2S puede producirse de forma endógena en lascélulas de mamíferos por dos vías: la vía enzimática y la vía no enzimática. Cuando se produce por la vía enzimática, su síntesis se lleva a cabo apartir de los aminoácidos L-cisteína o metionina mediante transulfuración y transmetilación. También se puede producir el H2S a partir donadores de grupos sulfuro como, por ejemplo, compuestos orgánicos que se encuentran presentes en algunos vegetales. Actualmente es bien conocido el papel del H2S como protector a nivel cerebral y cardiaco, y cada vez adquiere mayor relevancia su estudio como coadyuvante terapéutico en padecimientos metabólicos como la obesidad y la diabetes mellitus de tipo 2. El objetivo de esta revisión es examinar cómo impacta el aporte de donadores y precursores del sulfuro de hidrógeno por la dieta en la salud y la enfermedad. (AU)

Initially known for its deleterious health effects, hydrogen sulfide (H2S) has recently been recognized as a biologically important gas carrier, likenitric oxide and carbon monoxide. H2S is produced endogenously in mammalian cells by enzymatic and non-enzymatic pathways. When it isproduced by the enzymatic pathway, its synthesis is carried out from the amino acid L-cysteine through the transsulfuration pathway. It can alsobe produced endogenously from exogenous compounds that function as H2S donors as, for example, the naturally occurring organic donors foundin some plants. Currently, the role of H2S is well known as brain and cardiac protector, and its research as a therapeutic adjuvant in metabolicdiseases such as obesity and type-2 diabetes is becoming increasingly important. The objective of this review is to examine how the contributionof donors and precursors of hydrogen sulfide by the diet impacts health and disease. (AU)

[Diet as a source of hydrogen sulfide and its effects on health and disease]. / La dieta como fuente de sulfuro de hidrógeno y sus efectos en la salud y la enfermedad.

Introduction: Initially known for its deleterious health effects, hydrogen sulfide (H2S) has recently been recognized as a biologically important gas carrier, like nitric oxide and carbon monoxide. H2S is produced endogenously in mammalian cells by enzymatic and non-enzymatic pathways. When it is produced by the enzymatic pathway, its synthesis is carried out from the amino acid L-cysteine through the transsulfuration pathway. It can also be produced endogenously from exogenous compounds that function as H2S donors as, for example, the naturally occurring organic donors found in some plants. Currently, the role of S2H is well known as brain and cardiac protector, and its research as a therapeutic adjuvant in metabolic diseases such as obesity and type-2 diabetes is becoming increasingly important. The objective of this review is to examine how the contribution of donors and precursors of hydrogen sulfide by the diet impacts health and disease.

Introducción: Conocido originalmente por sus efectos deletéreos en la salud, recientemente se ha reconocido al sulfuro de hidrógeno (H2S) como un gasotransmisor de importancia biológica, al igual que el óxido nítrico y el monóxido de carbono. El H2S puede producirse de forma endógena en las células de mamíferos por dos vías: la vía enzimática y la vía no enzimática. Cuando se produce por la vía enzimática, su síntesis se lleva a cabo a partir de los aminoácidos L-cisteína o metionina mediante transulfuración y transmetilación. También se puede producir el H2S a partir donadores de grupos sulfuro como, por ejemplo, compuestos orgánicos que se encuentran presentes en algunos vegetales. Actualmente es bien conocido el papel del H2S como protector a nivel cerebral y cardiaco, y cada vez adquiere mayor relevancia su estudio como coadyuvante terapéutico en padecimientos metabólicos como la obesidad y la diabetes mellitus de tipo 2. El objetivo de esta revisión es examinar cómo impacta el aporte de donadores y precursores del sulfuro de hidrogeno por la dieta en la salud y la enfermedad.

Oxidative stress in early metabolic syndrome impairs cardiac RyR2 and SERCA2a activity and modifies the interplay of these proteins during Ca2+ waves.

We investigated how oxidative stress (OS) alters Ca2+ handling in ventricular myocytes in early metabolic syndrome (MetS) in sucrose-fed rats. The effects of N-acetyl cysteine (NAC) or dl-Dithiothreitol (DTT) on systolic Ca2+ transients (SCaTs), diastolic Ca2+ sparks (CaS) and Ca2+ waves (CaW), recorded by confocal techniques, and L-type Ca2+ current (ICa), assessed by whole-cell patch clamp, were evaluated in MetS and Control cells. MetS myocytes exhibited decreased SCaTs and CaS frequency but unaffected CaW propagation. In Control cells, NAC/DTT reduced RyR2/SERCA2a activity blunting SCaTs, CaS frequency and CaW propagation, suggesting that basal ROS optimised Ca2+ signalling by maintaining RyR2/SERCA2a function and that these proteins facilitate CaW propagation. Conversely, NAC/DTT in MetS recovered RyR2/SERCA2a function, improving SCaTs and CaS frequency, but unexpectedly decreasing CaW propagation. We hypothesised that OS decreases RyR2/SERCA2a activity at early MetS, and while decreased SERCA2a favours CaW propagation, diminished RyR2 restrains it.

Increased oxidative stress contributes to enhance brain amyloidogenesis and blunts energy metabolism in sucrose-fed rat: effect of AMPK activation.

Metabolic disturbances are linked to neurodegenerative diseases such as Alzheimer disease (AD). However, the cellular mechanisms underlying this connection are unclear. We evaluated the role of oxidative stress (OS), during early metabolic syndrome (MetS), on amyloidogenic processes in a MetS rat model induced by sucrose. MetS caused OS damage as indicated by serum and hypothalamus lipid peroxidation and elevated serum catalase activity. Tissue catalase and superoxide dismutase activity were unchanged by MetS, but gene expression of nuclear factor erythroid-derived 2-like 2 (NFE2L2), which up-regulates expression of antioxidant enzymes, was higher. Expression of amyloid-ß cleaving enzyme 1 (BACE-1) and amyloid precursor protein (APP), key proteins in the amyloidogenesis pathway, were slightly increased by sucrose-intake in the hippocampus and hypothalamus. Activation and expression of protein kinase B (PKB) and AMP-dependent protein kinase (AMPK), pivotal proteins in metabolism and energy signaling, were similarly affected in the hippocampus and hypothalamus of MetS rats. Brain creatine kinase activity decreased in brain tissues from rats with MetS, mainly due to irreversible oxidation. Chronic metformin administration partially reversed oxidative damage in sucrose-fed animals, together with increased AMPK activation; probably by modulating BACE-1 and NFE2L2. AMPK activation may be considered as a preventive therapy for early MetS and associated neurodegenerative diseases.

Steroidogenic impairment due to reduced ovarian transcription of cytochrome P450 side-chain-cleavage (P450scc) and steroidogenic acute regulatory protein (StAR) during experimental nephrotic syndrome.

The nephrotic syndrome is a renal disease characterized by proteinuria, hypoproteinemia, edema and hyperlipidemia. It has been reported that female nephrotic rats are characterized by loss of the oestrus cycle, follicle atresia, low gonadotropin and steroid concentrations; particularly, undetectable estradiol levels. Therefore, to determine the mechanisms involved in the ovarian steroidogenesis impairment, in this present study we evaluated the ovarian expression of the essential steroidogenesis components: cytochrome P450 side cholesterol chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR). The experiments were conducted in the rat experimental model of nephrosis induced by puromycin aminonucleoside (PAN) and in control groups. The evaluation of the expression of P450scc and StAR mRNA were performed during the acute phase of nephrosis as well as after the exogenous administration of 1 or 4 doses of human chorionic gonadotrophin (hCG), or a daily dose of FSH or FSH+hCG for 10 days. In addition, serum hormone concentrations, intra-ovarian steroid content, and the reproductive capacity were determined. The results revealed a decreased expression of mRNA of P450scc enzyme and StAR during nephrosis, and eventhough they increased after gonadotropins treatment, they did not conduce to a normal cycling rat period or fertility recovery. This study demonstrates that the mechanism by which ovarian steroid biosynthesis is altered during acute nephrosis involves damage at the P450scc and StAR mRNA synthesis and processing.