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1.
Environ Technol ; 41(14): 1837-1847, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30457937

RESUMEN

Pulp wash was used as substrate for the activity of ligninolytic enzymes of the fungus Pleurotus sajor-caju. Activity of laccase (Lac) and manganese peroxidase (MnP) as well as fungal biomass occurred under four conditions: different pulp wash concentrations, pH variation at the optimal pulp wash concentration, different glucose concentrations, and different concentrations of ammonium nitrate. The best enzyme activity and biomass production were obtained with in natura pulp wash and pH corrected to 5.0 (4884 IU/L Lac; 82 IU/L MnP; 25 g/100 mL biomass). However, the addition of glucose and ammonium nitrate to the pulp wash was not necessary for increasing the enzyme activity and biomass production. Efficient removal of pulp wash chemical oxygen demand (99.66%) and biochemical oxygen demand (83.27%) occurred after the mycoremediation with P. sajor-caju in the optimized conditions. Lactuca sativa L. seeds germination bioassay showed a four-fold reduction in the residue toxicity (EC50 28.72%) after the treatment with the fungus. Our findings are consistent with the notion that pulp wash is an excellent substrate for inducing the activity of ligninolytic enzymes and producing fungal biomass, and that the biological treatment is efficient to reduce effluent toxicity.


Asunto(s)
Pleurotus , Biodegradación Ambiental , Análisis de la Demanda Biológica de Oxígeno , Biomasa , Lacasa , Lignina , Peroxidasas
2.
Respir Physiol Neurobiol ; 263: 38-46, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30831241

RESUMEN

Hydrogen sulfide (H2S) is classically known for its toxic effects. More recently H2S has been documented as a neuromodulator. Here we investigated the central effects of aminooxyacetate (AOA; inhibitor of the H2S-synthesizing enzyme cystathionine ß-synthase, CBS) on cardiovascular, respiratory and thermoregulatory responses to hypercapnia in spontaneously hypertensive rats (SHR). To attain this goal we measured mean arterial pressure (MAP), heart rate (HR), ventilation (VE), and deep body temperature (Tb) of SHR and (normotensive) Wistar Kyoto (WKY) rats before and after microinjection of AOA (9 nmol/µL) or saline into the fourth ventricle immediately followed by 30-min hypercapnia exposure (7% inspired CO2). In saline-treated WKY rats, hypercapnia caused an increase in MAP accompanied by bradycardia, an increase in VE, and a drop in Tb. In AOA-treated WKY rats exposed to hypercapnia, the drug did not affect the increased MAP, potentiated the bradycardic response, attenuated the increased VE, and potentiated the drop in Tb. In saline-treated SHR, in comparison to the saline-treated WKY rats, hypercapnia elicited a minor, shorter-lasting increase in MAP with no changes in HR, evoked a greater increase in VE, and did not induce a drop in Tb. In AOA-treated SHR exposed to hypercapnia, the drug did not change the hypercapnia-induced cardiovascular and ventilatory responses while permitted a drop in Tb. Our findings indicate that AOA, an inhibitor of H2S production, modulates cardiorespiratory and thermoregulatory responses to hypercapnia in normotensive rats, whereas hypertension development in SHR is accompanied by suppression of the AOA effect on the cardiovascular and respiratory responses.


Asunto(s)
Ácido Aminooxiacético/farmacología , Presión Arterial , Regulación de la Temperatura Corporal , Temperatura Corporal , Inhibidores Enzimáticos/farmacología , Frecuencia Cardíaca , Sulfuro de Hidrógeno/antagonistas & inhibidores , Hipercapnia/fisiopatología , Frecuencia Respiratoria , Ácido Aminooxiacético/administración & dosificación , Animales , Presión Arterial/efectos de los fármacos , Presión Arterial/fisiología , Temperatura Corporal/efectos de los fármacos , Temperatura Corporal/fisiología , Regulación de la Temperatura Corporal/efectos de los fármacos , Regulación de la Temperatura Corporal/fisiología , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Frecuencia Cardíaca/fisiología , Masculino , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Frecuencia Respiratoria/efectos de los fármacos , Frecuencia Respiratoria/fisiología
3.
Brain Behav Immun ; 75: 119-128, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30261305

RESUMEN

Molecular hydrogen (H2) exerts anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Here we tested the hypothesis that H2 modulates cardiovascular, inflammatory, and thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at different doses (0.1 or 1.5 mg/kg, intravenously, to induce mild or severe SI) in male Wistar rats (250-300 g). LPS or saline was injected immediately before the beginning of 360-minute inhalation of H2 (2% H2, 21% O2, balanced with nitrogen) or room air (21% O2, balanced with nitrogen). Deep body temperature (Tb) was measured by dataloggers pre-implanted in the peritoneal cavity. H2 caused no change in cardiovascular, inflammatory parameters, and Tb of control rats (treated with saline). During mild SI, H2 reduced plasma surges of proinflammatory cytokines (TNF-α and IL-6) while caused an increase in plasma IL-10 (anti-inflammatory cytokine) and prevented fever. During severe SI, H2 potentiated hypothermia, and prevented fever and hypotension, which coincided with reduced plasma nitric oxide (NO) production. Moreover, H2 caused a reduction in surges of proinflammatory cytokines (plasma TNF-α and IL-1ß) and prostaglandin E2 [(PGE2), in plasma and hypothalamus], and an increase in plasma IL-10. These data are consistent with the notion that H2 blunts fever in mild SI, and during severe SI potentiates hypothermia, prevents hypotension reducing plasma NO production, and exerts anti-inflammatory effects strong enough to prevent fever by altering febrigenic signaling and ultimately down-modulating hypothalamic PGE2 production.


Asunto(s)
Hidrógeno/metabolismo , Hipotermia/metabolismo , Inflamación/metabolismo , Animales , Temperatura Corporal/fisiología , Endotoxinas/metabolismo , Fiebre/metabolismo , Hipotensión/metabolismo , Hipotálamo/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , Masculino , Óxido Nítrico/metabolismo , Ratas , Ratas Wistar , Sepsis/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
4.
Exp Physiol ; 103(3): 397-407, 2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29210120

RESUMEN

NEW FINDINGS: What is the central question of this study? In fever, the most striking response in the acute phase reaction of systemic inflammation, plasma H2 S concentration increases. However, the role of endogenous peripheral H2 S in fever is unknown. What is the main finding and its importance? Endogenous peripheral H2 S is permissive for increased brown adipose tissue thermogenesis to maintain thermal homeostasis in cold environments as well as to mount fever. This finding expands the physiological role of the gaseous modulator as a key regulator of thermal control in health (thermal homeostasis) and disease (fever in systemic inflammation). ABSTRACT: In recent years, hydrogen sulfide (H2 S) has been reported as a gaseous modulator acting in several tissues in health and disease. In animal models of systemic inflammation, the plasma H2 S concentration increases in response to endotoxin (bacterial lipopolysaccharide, LPS). The most striking response in the acute phase reaction of systemic inflammation is fever, but we found no reports of the peripheral action of H2 S on this thermoregulatory response. We aimed at investigating whether endogenous systemic H2 S modulates LPS-induced fever. A temperature datalogger capsule was inserted in the abdominal cavity of male Wistar rats (220-270 g) to record body core temperature. These animals received an i.p. injection of a systemic H2 S inhibitor (propargylglycine; 50 or 75 mg kg-1 ), immediately followed by an i.p. injection of LPS (50 or 2500 µg kg-1 ), and were exposed to different ambient temperatures (16, 22 or 27°C). At 22°C, but not at 27°C, propargylglycine at 75 mg kg-1 significantly attenuated (P < 0.0001) the fever induced by LPS (50 µg kg-1 ), indicating a modulatory (permissive) action of endogenous peripheral H2 S on brown adipose tissue (BAT) thermogenesis. Evidence on the modulatory role of peripheral H2 S in BAT thermogenesis was strengthened when we discarded (i) the possible influence of the gas on febrigenic signalling (when measuring plasma cytokines), and (ii) its interaction with the nitric oxide pathway, and mainly when (iii) we carried out physiological and pharmacological activations of BAT. Endogenous peripheral H2 S modulates (permits) BAT activity not only in fever but also during maintenance of thermal homeostasis in cold environments.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Regulación de la Temperatura Corporal/fisiología , Sulfuro de Hidrógeno/metabolismo , Termogénesis/fisiología , Alquinos/farmacología , Animales , Regulación de la Temperatura Corporal/efectos de los fármacos , Glicina/análogos & derivados , Glicina/farmacología , Sulfuro de Hidrógeno/antagonistas & inhibidores , Masculino , Ratas , Ratas Wistar , Termogénesis/efectos de los fármacos
5.
PLoS One ; 12(1): e0170468, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28118407

RESUMEN

We tested the hypothesis that the neuromodulator hydrogen sulfide (H2S) in the preoptic area (POA) of the hypothalamus modulates the febrigenic signaling differently in sedentary and trained rats. Besides H2S production rate and protein expressions of H2S-related synthases cystathionine ß-synthase (CBS), 3-mercaptopyruvate sulfurtransferase (3-MPST) and cystathionine γ-lyase (CSE) in the POA, we also measured deep body temperature (Tb), circulating plasma levels of cytokines and corticosterone in an animal model of systemic inflammation. Rats run on a treadmill before receiving an intraperitoneal injection of lipopolysaccharide (LPS, 100 µg/kg) or saline. The magnitude of changes of Tb during the LPS-induced fever was found to be similar between sedentary and trained rats. In sedentary rats, H2S production was not affected by LPS. Conversely, in trained rats LPS caused a sharp increase in H2S production rate that was accompanied by an increased CBS expression profile, whereas 3-MPST and CSE expressions were kept relatively constant. Sedentary rats showed a significant LPS-induced release of cytokines (IL-1ß, IL-6, and TNF-α) which was virtually abolished in the trained animals. Correlation between POA H2S and IL-6 as well as TNF-α was observed. Corticosterone levels were augmented after LPS injection in both groups. We found correlations between H2S and corticosterone, and corticosterone and IL-1ß. These data are consistent with the notion that the responses to systemic inflammation are tightly regulated through adjustments in POA H2S production which may play an anti-inflammatory role downmodulating plasma cytokines levels and upregulating corticosterone release.


Asunto(s)
Regulación de la Temperatura Corporal/fisiología , Fiebre/fisiopatología , Sulfuro de Hidrógeno/metabolismo , Condicionamiento Físico Animal/fisiología , Área Preóptica/metabolismo , Animales , Corticosterona/sangre , Corticosterona/metabolismo , Cistationina betasintasa/biosíntesis , Cistationina betasintasa/genética , Cistationina gamma-Liasa/biosíntesis , Cistationina gamma-Liasa/genética , Citocinas/sangre , Citocinas/metabolismo , Endotoxemia/inducido químicamente , Endotoxemia/complicaciones , Endotoxemia/fisiopatología , Endotoxinas/toxicidad , Inducción Enzimática , Fiebre/etiología , Inflamación , Masculino , Área Preóptica/fisiopatología , Ratas , Ratas Wistar , Carrera , Conducta Sedentaria , Sulfurtransferasas/biosíntesis , Sulfurtransferasas/genética
6.
Can J Physiol Pharmacol ; 95(2): 157-162, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27901369

RESUMEN

Spontaneously hypertensive rats (SHR) display autonomic imbalance and abnormal body temperature (Tb) adjustments. Hydrogen sulfide (H2S) modulates hypoxia-induced hypothermia, but its role in SHR thermoregulation is unknown. We tested the hypothesis that SHR display peculiar thermoregulatory response to hypoxia and that endogenous H2S overproduced in the caudal nucleus of the solitary tract (NTS) of SHR modulates this response. SHR and Wistar rats were microinjected into the fourth ventricle with aminooxyacetate (AOA, H2S-synthezing enzyme inhibitor) or sodium sulfide (Na2S, H2S donor) and exposed to normoxia (21% inspired O2) or hypoxia (10% inspired O2, 30 min). Tb was continuously measured, and H2S production rate was assessed in caudal NTS homogenates. In both groups, AOA, Na2S, or saline (i.e., control; 1 µL) did not affect euthermia. Hypoxia caused similar decreases in Tb in both groups. AOA presented a longer latency to potentiate hypoxic hypothermia in SHR. Caudal NTS H2S production rate was higher in SHR. We suggest that increased bioavailability of H2S in the caudal NTS of SHR enables the adequate modulation of excitability of peripheral chemoreceptor-activated NTS neurons that ultimately induce suppression of brown adipose tissue thermogenesis, thus accounting for the normal hypoxic hypothermia.


Asunto(s)
Regulación de la Temperatura Corporal , Sulfuro de Hidrógeno/metabolismo , Hipotermia Inducida , Hipoxia/fisiopatología , Ácido Aminooxiacético/administración & dosificación , Ácido Aminooxiacético/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Hipoxia/complicaciones , Masculino , Microinyecciones , Ratas , Ratas Endogámicas SHR , Núcleo Solitario/metabolismo , Núcleo Solitario/fisiopatología , Sulfuros/administración & dosificación , Sulfuros/farmacología
7.
Brain Res ; 1650: 218-223, 2016 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-27592137

RESUMEN

Thermoregulatory responses to lipopolysaccharide (LPS) are affected by modulators that increase (propyretic) or decrease (cryogenic) body temperature (Tb). We tested the hypothesis that central hydrogen sulfide (H2S) acts as a thermoregulatory modulator and that H2S production in the anteroventral preoptic region of the hypothalamus (AVPO) is increased during hypothermia and decreased during fever induced by bacterial lipopolysaccharide (LPS, 2.5mg/kg i.p.) in rats kept at an ambient temperature of 25°C. Deep Tb was recorded before and after pharmacological inhibition of the enzyme cystathionine ß-synthase (CBS - responsible for H2S endogenous production in the brain) combined or not with LPS administration. To further investigate the mechanisms responsible for these thermoregulatory adjustments, we also measured prostaglandin D2 (PGD2) production in the AVPO. LPS caused typical hypothermia followed by fever. Levels of AVPO H2S were significantly increased during hypothermia when compared to both euthermic and febrile rats. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) neither affected Tb nor basal PGD2 production during euthermia. In LPS-treated rats, AOA caused increased Tb values during hypothermia, along with enhanced PGD2 production. We conclude that the gaseous messenger H2S modulates hypothermia during endotoxic shock, acting as a cryogenic molecule.


Asunto(s)
Temperatura Corporal/efectos de los fármacos , Sulfuro de Hidrógeno/farmacología , Choque Séptico/fisiopatología , Ácido Aminooxiacético , Animales , Regulación de la Temperatura Corporal/fisiología , Cistationina betasintasa/metabolismo , Fiebre/inducido químicamente , Hipotálamo/metabolismo , Hipotermia/fisiopatología , Hipoxia , Lipopolisacáridos , Masculino , Microinyecciones , Área Preóptica/metabolismo , Ratas , Ratas Wistar
8.
Compr Physiol ; 4(4): 1301-38, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25428845

RESUMEN

Deep body temperature (Tb) is kept relatively constant despite a wide range of ambient temperature variation. Nevertheless, in particular situations it is beneficial to decrease or to increase Tb in a regulated manner. Under hypoxia for instance a regulated drop in Tb (anapyrexia) is key to reduce oxygen demand of tissues when oxygen availability is diminished, leading to an increased survival rate in a number of species when experiencing low levels of inspired oxygen. On the other hand, a regulated rise in Tb (fever) assists the healing process. These regulated changes in Tb are mediated by the brain, where afferent signals converge and the most important regions for the control of Tb are found. The brain (particularly some hypothalamic structures located in the preoptic area) modulates efferent activities that cause changes in heat production (modulating brown adipose tissue activity and perfusion, for instance) and heat loss (modulating tail skin vasculature blood flow, for instance). This review highlights key advances about the role of the gaseous neuromodulators nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S) in thermoregulation, acting both on the brain and the periphery.


Asunto(s)
Regulación de la Temperatura Corporal , Monóxido de Carbono/metabolismo , Sulfuro de Hidrógeno/metabolismo , Óxido Nítrico/metabolismo , Oxígeno/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Pardo/fisiología , Animales , Humanos , Hipotálamo/metabolismo , Hipotálamo/fisiología
9.
Brain Res Bull ; 108: 94-9, 2014 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25262576

RESUMEN

Hypoxia evokes a regulated decrease in deep body temperature (Tb). Hydrogen sulfide (H2S), a signaling molecule that belongs to the gasotransmitter family, has been demonstrated to participate in several brain-mediated responses. Rostral ventrolateral medulla (RVLM) is a brainstem region involved in thermoregulation. Recently, it has been shown that exogenous H2S modulates RVLM activity. In the present study, we investigated whether endogenously produced H2S in the RVLM plays a role in the control of hypoxia-induced hypothermia. Tb was measured before and after bilateral microinjection of aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine ß-synthase, CBS, inhibitor) or vehicle into the RVLM followed by a 60-min normoxia (21% inspired O2) or hypoxia (7% inspired O2) exposure. Microinjection of AOA or vehicle did not change Tb during normoxia. Exposure to hypoxia evoked a typical decrease in Tb. Microinjection of AOA (2 pmol) into the RVLM followed by hypoxia significantly attenuated the decrease in Tb. Thus, endogenous H2S in the RVLM seems to play no role in the maintenance of basal Tb, whereas during hypoxia this gas plays a cryogenic role. Moreover, RVLM homogenates of rats exposed to hypoxia exhibited a decreased rate of H2S production. Our data are consistent with the notion that during hypoxia H2S synthesis is diminished in the RVLM facilitating hypothermia.


Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Hipotermia/fisiopatología , Hipoxia/fisiopatología , Bulbo Raquídeo/fisiopatología , Ácido Aminooxiacético/farmacología , Animales , Temperatura Corporal/efectos de los fármacos , Cistationina betasintasa/antagonistas & inhibidores , Cistationina betasintasa/metabolismo , Inhibidores Enzimáticos/farmacología , Hipotermia/etiología , Hipoxia/complicaciones , Masculino , Bulbo Raquídeo/efectos de los fármacos , Ratas , Ratas Wistar
10.
Respir Physiol Neurobiol ; 200: 97-104, 2014 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-24953676

RESUMEN

Hydrogen sulfide (H2S) is now recognized as a new gaseous transmitter involved in several brain-mediated responses. The rostral ventrolateral medulla (RVLM)/Bötzinger complex is a region in the brainstem that is involved in cardiovascular and respiratory functions. Recently, it has been shown that exogenous H2S in the RVLM modulates autonomic function and thus blood pressure. In the present study, we investigated whether H2S, endogenously produced in the RVLM/Bötzinger complex, plays a role in the control of hypoxia-induced hyperventilation. Ventilation (VE) was measured before and after bilateral microinjection of Na2S (H2S donor, 0.04, 1 and 2 pmol/100 nl) or aminooxyacetate (AOA, 0.2, 1 and 2 pmol/100 nl, a cystathionine ß-synthase, CBS, inhibitor) into the RVLM/Bötzinger complex followed by a 60-min period of hypoxia (7% inspired O2) or normoxia exposure. Control rats received microinjection of vehicle. Microinjection of vehicle, AOA or Na2S did not change VE in normoxic conditions. Exposure to hypoxia evoked a typical increase in VE. Microinjection of Na2S (2 pmol) followed by hypoxia exposure attenuated the hyperventilation. Conversely, microinjection of AOA (2 pmol) into the RVLM/Bötzinger complex caused an increase in the hypoxia-induced hyperventilation. Thus, endogenous H2S in the RVLM/Bötzinger complex seems to play no role in the maintenance of basal pulmonary ventilation during normoxia whereas during hypoxia H2S has a downmodulatory function. Homogenates of RVLM/Bötzinger complex of animals previously exposed to hypoxia for 60 min exhibited a decreased rate of H2S production. Our data are consistent with the notion that the gaseous messenger H2S synthesis is downregulated in the RVLM/Bötzinger complex during hypoxia favoring hyperventilation.


Asunto(s)
Sulfuro de Hidrógeno/metabolismo , Hiperventilación/fisiopatología , Hipoxia/fisiopatología , Bulbo Raquídeo/fisiopatología , Ácido Aminooxiacético/farmacología , Animales , Catéteres de Permanencia , Fármacos del Sistema Nervioso Central/farmacología , Cistationina betasintasa/antagonistas & inhibidores , Cistationina betasintasa/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/farmacología , Hiperventilación/tratamiento farmacológico , Hiperventilación/etiología , Hipoxia/complicaciones , Hipoxia/tratamiento farmacológico , Masculino , Bulbo Raquídeo/efectos de los fármacos , Microinyecciones , Pletismografía , Ratas Wistar , Sulfatos/farmacología
11.
Eur J Pharmacol ; 738: 49-56, 2014 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-24876060

RESUMEN

Hydrogen sulfide (H2S) is a gasotransmitter synthesized in peripheral tissues by the enzyme cystathionine gamma-lyase (CSE). This gas has been documented to be involved in a wide variety of processes including inflammation and nociception. The aim of the present study was to investigate the role of the peripheral H2S pathway in nociceptive response to the orofacial formalin experimental model of pain. Orofacial pain was induced by subcutaneous injection of formalin (1.5%, 50 µl) into the upper lip of rats, and the time spent rubbing the face was measured at 3-min intervals for 45 min. Formalin induced a marked biphasic pain (first phase: 0-3 min; second phase: 15-33 min). Pretreatment with H2S donor (Na2S; 90 µmol/kg), CSE inhibitor (propargylglycine; 26.5 and 88.4 µmol/kg), or a preferential blocker of T-type Ca(2+) channels (mibefradil; 0.28 and 2.81 µmol/kg) attenuated the second phase of face rubbing when injected locally as well as systemically. Pretreatment with a selective blocker of K(+)ATP channels (glybenclamide; 2.81 µmol/kg) suppressed the Na2S-mediated attenuation of the formalin-induced pain second phase. Taken together these results suggest that endogenously produced H2S plays a pronociceptive role probably via T-type Ca(2+) channels, whereas exogenous H2S exerts antinociceptive effects mediated by K(+)ATP channels.


Asunto(s)
Dolor Facial/inducido químicamente , Dolor Facial/metabolismo , Formaldehído/efectos adversos , Sulfuro de Hidrógeno/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Canales de Calcio Tipo T/metabolismo , Dolor Facial/psicología , Canales KATP/metabolismo , Labio/efectos de los fármacos , Labio/metabolismo , Masculino , Nocicepción/efectos de los fármacos , Ratas
12.
Can J Physiol Pharmacol ; 91(10): 861-5, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24144058

RESUMEN

Heme oxygenase (HO)-1 has antioxidant and cytoprotective properties if properly expressed, whereas nitric oxide (NO) impairs tissue perfusion when greatly increased in the blood circulation. Here we hypothesized that the NO and HO-1 systems are altered during lipopolysaccharide (LPS) tolerance, and that glucocorticoids are crucial modulators of systemic NO production and hepatic HO-1 expression during this intriguing phenomenon of cellular reprogramming. Adrenalectomized (ADX) rats with or without administration of dexamethasone (DEX) were challenged with LPS for 3 consecutive days. The plasma levels of corticosterone and nitrate (NOx), and expression of HO-1 protein were assessed. During tolerance, corticosterone levels were elevated, NOx reduced, and HO-1 overexpressed. ADX rats challenged with LPS for 3 consecutive days exhibited a ~9-fold increase in NOx and a ~6-fold increase in HO-1, reverted by DEX. Our findings strongly support the fact that glucocorticoids downregulate systemic NO synthesis and counteract hepatic HO-1 overexpression during LPS tolerance.


Asunto(s)
Dexametasona/administración & dosificación , Endotoxemia/enzimología , Glucocorticoides/administración & dosificación , Hemo Oxigenasa (Desciclizante)/metabolismo , Terapia de Reemplazo de Hormonas , Hígado/efectos de los fármacos , Óxido Nítrico/metabolismo , Adrenalectomía , Animales , Corticosterona/sangre , Modelos Animales de Enfermedad , Regulación hacia Abajo , Endotoxemia/sangre , Endotoxemia/inducido químicamente , Fiebre/inducido químicamente , Fiebre/enzimología , Inyecciones Subcutáneas , Lipopolisacáridos , Hígado/enzimología , Masculino , Nitratos/sangre , Ratas , Ratas Wistar , Factores de Tiempo , Regulación hacia Arriba
13.
Exp Neurol ; 240: 88-95, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23153577

RESUMEN

Hydrogen sulfide (H(2)S) is a gaseous neuromodulator endogenously produced in the brain by the enzyme cystathionine ß-synthase (CBS). We tested the hypothesis that H(2)S acts within the anteroventral preoptic region of the hypothalamus (AVPO) modulating the production of prostaglandin (PG) E(2) (the proximal mediator of fever) and cyclic AMP (cAMP). To this end, we recorded deep body temperature (Tb) of rats before and after pharmacological modulation of the CBS-H(2)S system combined or not with lipopolysaccharide (LPS) exposure, and measured the levels of H(2)S, cAMP, and PGE(2) in the AVPO during systemic inflammation. Intracerebroventricular (icv) microinjection of aminooxyacetate (AOA, a CBS inhibitor; 100 pmol) did not affect basal PGE(2) production and Tb, but enhanced LPS-induced PGE(2) production and fever, indicating that endogenous H(2)S plays an antipyretic role. In agreement, icv microinjection of a H(2)S donor (Na(2)S; 260 nmol) reduced the LPS-induced PGE(2) production and fever. Interestingly, we observed that the AVPO levels of H(2)S were decreased following the immunoinflammatory challenge. Furthermore, fever was associated with decreased levels of AVPO cAMP and increased levels of AVPO PGE(2). The LPS-induced decreased levels of cAMP were reduced to a lesser extent by the H(2)S donor. The LPS-induced PGE(2) production was potentiated by AOA (the CBS inhibitor) and inhibited by the H(2)S donor. Our data are consistent with the notion that the gaseous messenger H(2)S synthesis is downregulated during endotoxemia favoring PGE(2) synthesis and lowering cAMP levels in the preoptic hypothalamus.


Asunto(s)
Dinoprostona/biosíntesis , Endotoxemia/metabolismo , Fiebre/metabolismo , Sulfuro de Hidrógeno/metabolismo , Área Preóptica/metabolismo , Animales , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Endotoxemia/inducido químicamente , Fiebre/inducido químicamente , Sulfuro de Hidrógeno/farmacología , Masculino , Ratas , Ratas Wistar
14.
Peptides ; 32(11): 2372-6, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21377501

RESUMEN

Ghrelin is a gut-derived peptide that plays a role in energy homeostasis. Recent studies have implicated ghrelin in systemic inflammation, showing increased plasma ghrelin levels after endotoxin (lipopolysaccharide, LPS) administration. The aims of this study were (1) to test the hypothesis that ghrelin administration affects LPS-induced fever; and (2) to assess the putative effects of ghrelin on plasma corticosterone secretion and preoptic region prostaglandin (PG) E(2) levels in euthermic and febrile rats. Rats were implanted with a temperature datalogger capsule in the peritoneal cavity to record body core temperature. One week later, they were challenged with LPS (50 µg/kg, intraperitoneal, i.p.) alone or combined with ghrelin (0.1mg/kg, i.p.). In another group of rats, plasma corticosterone and preoptic region PGE(2) levels were measured 2h after injections. In euthermic animals, systemic administration of ghrelin failed to elicit any thermoregulatory effect, and caused no significant changes in basal plasma corticosterone and preoptic region PGE(2) levels. LPS caused a typical febrile response, accompanied by increased plasma corticosterone and preoptic PGE(2) levels. When LPS administration was combined with ghrelin fever was attenuated, corticosterone secretion further increased, and the elevated preoptic PGE(2) levels were relatively reduced, but a correlation between these two variables (corticosterone and PGE(2)) failed to exist. The present data add ghrelin to the neurochemical milieu controlling the immune/thermoregulatory system acting as an antipyretic molecule. Moreover, our findings also support the notion that ghrelin attenuates fever by means of a direct effect of the peptide reducing PGE(2) production in the preoptic region.


Asunto(s)
Antipiréticos/administración & dosificación , Dinoprostona/metabolismo , Fiebre/tratamiento farmacológico , Ghrelina/administración & dosificación , Área Preóptica/metabolismo , Animales , Antipiréticos/uso terapéutico , Temperatura Corporal , Regulación de la Temperatura Corporal/efectos de los fármacos , Regulación de la Temperatura Corporal/fisiología , Corticosterona/sangre , Corticosterona/metabolismo , Fiebre/inducido químicamente , Fiebre/metabolismo , Ghrelina/uso terapéutico , Inyecciones Intraperitoneales , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/efectos adversos , Masculino , Área Preóptica/efectos de los fármacos , Ratas , Ratas Wistar
15.
J Neuroimmunol ; 225(1-2): 77-81, 2010 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-20546941

RESUMEN

Immune challenges during neonatal period may permanently program immune responses later in life, including endotoxin fever. We tested the hypothesis that neonatal endotoxin exposure affects stress fever in adult rats. In control rats (treated with saline as neonates; nSal) body temperature peaked approximately 1.5 degrees C during open-field stress, whereas in rats exposed to endotoxin (lipopolysaccharide, LPS) as neonates (nLPS) stress fever was significantly attenuated. Following stress, plasma corticosterone levels significantly increased from 74.29+/-7.05 ng ml(-1) to 226.29+/-9.87 ng ml(-1) in nSal rats, and from 83.43+/-10.31 ng ml(-1) to 324.7+/-36.87 ng ml(-1) in nLPS rats. Animals treated with LPS as neonates and adrenalectomized one week before experimentation no longer displayed the attenuated febrile response to stress. This attenuated stress fever caused by an increased corticosterone secretion is likely to be linked to an inhibitory effect of glucocorticoids on cyclooxygenase activity/PGE(2) production in preoptic/anteroventral third ventricular region (AV3V) since stress failed to cause a significant increase in PGE(2) in nLPS rats, and this effect was reverted by adrenalectomy. Altogether, the present results indicate that endogenous glucocorticoids are key modulators of the attenuated stress fever in adult rats treated with LPS as neonates, and they act downregulating PGE(2) production in AV3V. Moreover, our findings also support the notion that neonatal immune stimulus affects programming of stress responses during adulthood, despite the fact that inflammation and stress are two distinct processes mediated largely by different neurobiological mechanisms.


Asunto(s)
Dinoprostona/metabolismo , Endotoxinas/toxicidad , Fiebre/etiología , Fiebre/fisiopatología , Glucocorticoides/sangre , Lipopolisacáridos/toxicidad , Estrés Psicológico/complicaciones , Adrenalectomía/métodos , Análisis de Varianza , Animales , Animales Recién Nacidos , Temperatura Corporal/efectos de los fármacos , Dexametasona/uso terapéutico , Modelos Animales de Enfermedad , Conducta Exploratoria/efectos de los fármacos , Fiebre/sangre , Fiebre/patología , Masculino , Ratas , Ratas Wistar , Tercer Ventrículo/efectos de los fármacos , Tercer Ventrículo/metabolismo
16.
Exp Physiol ; 95(6): 669-77, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-20176679

RESUMEN

Nitric oxide has been reported to modulate fever in the brain. However, the sites where NO exerts this modulation remain somewhat unclear. Locus coeruleus (LC) neurons express not only nitric oxide synthase (NOS) but also soluble guanylyl cyclase (sGC). In the present study, we evaluated in vivo and ex vivo the putative role of the LC NO-cGMP pathway in fever. To this end, deep body temperature was measured before and after pharmacological modulations of the pathway. Moreover, nitrite/nitrate (NOx) and cGMP levels in the LC were assessed. Conscious rats were microinjected within the LC with a non-selective NOS inhibitor (N(G)-monomethyl-l-arginine acetate), a NO donor (NOC12), a sGC inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) or a cGMP analogue (8-bromo-cGMP) and injected intraperitoneally with endotoxin. Inhibition of NOS or sGC before endotoxin injection significantly increased the latency to the onset of fever. During the course of fever, inhibition of NOS or sGC attenuated the febrile response, whereas microinjection of NOC12 or 8-bromo-cGMP increased the response. These findings indicate that the LC NO-cGMP pathway plays a propyretic role. Furthermore, we observed a significant increase in NOx and cGMP levels, indicating that the febrile response to endotoxin is accompanied by stimulation of the NO-cGMP pathway in the LC.


Asunto(s)
Fiebre/inducido químicamente , Fiebre/fisiopatología , Locus Coeruleus/metabolismo , Animales , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacología , Endotoxinas/farmacología , Fiebre/metabolismo , Guanilato Ciclasa/antagonistas & inhibidores , Locus Coeruleus/efectos de los fármacos , Masculino , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/fisiología , Compuestos Nitrosos/farmacología , Oxadiazoles/farmacología , Quinoxalinas/farmacología , Ratas , Ratas Wistar , Receptores Citoplasmáticos y Nucleares/antagonistas & inhibidores , Guanilil Ciclasa Soluble
17.
Clin Exp Pharmacol Physiol ; 34(11): 1156-9, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17880370

RESUMEN

1. The aim of the present study was to evaluate the effects of peripheral chemoreceptor activation on myocardial contractility in an anaesthetic-free decerebrated rat preparation. 2. In the decerebrated and retrogradely perfused working heart-brainstem preparation, we recorded phrenic nerve activity, left ventricular (LV) pressure (microtip Millar catheter), LV dP/dT, heart rate and aortic perfusion pressure before and after activating peripheral chemoreceptors with bolus intra-arterial injections of KCN. 3. Without cardiac pacing, chemoreflex activation caused falls in heart rate (-108 +/- 21 b.p.m.) and complex polyphasic changes in LV pressure and LV dP/dT. If the heart was paced, chemoreflex activation caused significant rises in LP pressure (+16 +/- 3 mmHg) and LV dP/dt (+778 +/- 93 mmHg/s). These positive inotropic effects were significantly and substantially attenuated by beta-adrenoceptor blockade with atenolol. In all instances, chemoreflex activation elicited potent tachypnoeic responses. 4. In conclusion, activation of peripheral chemoreceptors in non-anaesthetized rats evokes a positive inotropic response that is sympathetically mediated. This observation may be relevant for the evaluation of neurally induced effects of acute hypoxia on the ventricular myocardium.


Asunto(s)
Tronco Encefálico/fisiología , Células Quimiorreceptoras/metabolismo , Corazón/inervación , Contracción Miocárdica , Reflejo , Sistema Nervioso Simpático/fisiología , Función Ventricular Izquierda , Antagonistas de Receptores Adrenérgicos beta 1 , Antagonistas Adrenérgicos beta/farmacología , Animales , Atenolol/farmacología , Presión Sanguínea , Tronco Encefálico/efectos de los fármacos , Estimulación Cardíaca Artificial , Cardiotónicos/farmacología , Células Quimiorreceptoras/efectos de los fármacos , Estado de Descerebración , Corazón/efectos de los fármacos , Frecuencia Cardíaca , Masculino , Contracción Miocárdica/efectos de los fármacos , Perfusión , Nervio Frénico/fisiología , Cianuro de Potasio/farmacología , Ratas , Ratas Wistar , Receptores Adrenérgicos beta 1/metabolismo , Reflejo/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacos , Presión Ventricular
18.
J Physiol ; 581(Pt 3): 1129-45, 2007 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-17395636

RESUMEN

Peripheral chemoreflex activation with potassium cyanide (KCN) in awake rats or in the working heart-brainstem preparation (WHBP) produces: (a) a sympathoexcitatory/pressor response; (b) bradycardia; and (c) an increase in the frequency of breathing. Our main aim was to evaluate neurotransmitters involved in mediating the sympathoexcitatory component of the chemoreflex within the nucleus tractus solitarii (NTS). In previous studies in conscious rats, the reflex bradycardia, but not the pressor response, was reduced by antagonism of either ionotropic glutamate or purinergic P2 receptors within the NTS. In the present study we evaluated a possible dual role of both P2 and NMDA receptors in the NTS for processing the sympathoexcitatory component (pressor response) of the chemoreflex in awake rats as well as in the WHBP. Simultaneous blockade of ionotropic glutamate receptors and P2 receptors by sequential microinjections of kynurenic acid (KYN, 2 nmol (50 nl)(-1)) and pyridoxalphosphate-6-azophenyl-2',4'-disulphonate (PPADS, 0.25 nmol (50 nl)(-1)) into the commissural NTS in awake rats produced a significant reduction in both the pressor (+38+/-3 versus +8+/-3 mmHg) and bradycardic responses (-172+/-18 versus -16+/-13 beats min(-1); n=13), but no significant changes in the tachypnoea measured using plethysmography (270+/-30 versus 240+/-21 cycles min(-1), n=7) following chemoreflex activation in awake rats. Control microinjections of saline produced no significant changes in these reflex responses. In WHBP, microinjection of KYN (2 nmol (20 nl)(-1)) and PPADS (1.6 nmol (20 nl)(-1)) into the commissural NTS attenuated significantly both the increase in thoracic sympathetic activity (+52+/-2% versus +17+/-1%) and the bradycardic response (-151+/-17 versus -21+/-3 beats min(-1)) but produced no significant changes in the increase of the frequency of phrenic nerve discharge (+0.24+/-0.02 versus +0.20+/-0.02 Hz). The data indicate that combined microinjections of PPADS and KYN into the commissural NTS in both awake rats and the WHBP are required to produce a significant reduction in the sympathoexcitatory response (pressor response) to peripheral chemoreflex activation. We conclude that glutamatergic and purinergic mechanisms are part of the complex neurotransmission system of the sympathoexcitatory component of the chemoreflex at the level of the commissural NTS.


Asunto(s)
Adenosina Trifosfato/metabolismo , Tronco Encefálico/metabolismo , Células Quimiorreceptoras/metabolismo , Ácido Glutámico/metabolismo , Corazón/inervación , Reflejo , Núcleo Solitario/metabolismo , Sistema Nervioso Simpático/metabolismo , Adenosina Trifosfato/análogos & derivados , Adenosina Trifosfato/farmacología , Animales , Antihipertensivos/farmacología , Presión Sanguínea , Tronco Encefálico/citología , Tronco Encefálico/efectos de los fármacos , Células Quimiorreceptoras/efectos de los fármacos , Antagonistas de Aminoácidos Excitadores/farmacología , Corazón/efectos de los fármacos , Frecuencia Cardíaca , Ácido Quinurénico/farmacología , Masculino , Neuronas Aferentes/metabolismo , Nitroprusiato/farmacología , Cianuro de Potasio/farmacología , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacología , Ratas , Ratas Wistar , Receptores de Glutamato/metabolismo , Receptores Purinérgicos P2/metabolismo , Reflejo/efectos de los fármacos , Mecánica Respiratoria , Núcleo Solitario/citología , Núcleo Solitario/efectos de los fármacos , Sistema Nervioso Simpático/citología , Sistema Nervioso Simpático/efectos de los fármacos , Vigilia
19.
Exp Physiol ; 91(6): 1025-31, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16959820

RESUMEN

In the present study, we tested the hypothesis that chronic intermittent hypoxia (CIH) produces changes in the autonomic and respiratory responses to acute peripheral chemoreflex activation. To attain this goal, 3-week-old rats were exposed to 10 days of CIH (6% O(2) for 40 s at 9 min intervals; 8 h day(-1)). They were then used to obtain a working heart-brainstem preparation and, using this unanaesthetized experimental preparation, the chemoreflex was activated with potassium cyanide (0.05%, injected via the perfusion system), and the thoracic sympathetic nerve activity (tSNA), heart rate and phrenic nerve discharge (PND) were recorded. Rats subjected to CIH (n = 12), when compared with control animals (n = 12), presented the following significant changes in response to chemoreflex activation: (a) an increase in tSNA (78 +/- 4 versus 48 +/- 3%); (b) a long-lasting increase in the frequency of the PND at 20 (0.52 +/- 0.03 versus 0.36 +/- 0.03 Hz) and 30 s (0.40 +/- 0.02 versus 0.31 +/- 0.02 Hz) after the stimulus; and (c) a greater bradycardic response (-218 +/- 20 versus -163 +/- 16 beats min(-1)). These results indicate that the autonomic and respiratory responses to chemoreflex activation in juvenile rats previously submitted to CIH are greatly increased.


Asunto(s)
Células Quimiorreceptoras/fisiología , Hipoxia/fisiopatología , Sistema Nervioso Periférico/fisiología , Sistema Nervioso Simpático/fisiología , Animales , Animales Recién Nacidos , Sistema Nervioso Autónomo/fisiología , Peso Corporal/fisiología , Bradicardia/fisiopatología , Células Quimiorreceptoras/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Frecuencia Cardíaca/fisiología , Nervio Frénico/fisiología , Cianuro de Potasio/farmacología , Ratas , Sistema Respiratorio/efectos de los fármacos
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