RESUMEN
Telfairia occidentalis possesses high antioxidant activity. However, the antioxidant components of the plant have not yet been identified. This study was undertaken to identify the phenolics in the leaf of the plant. Extract and fractions of the leaf of the plant were analysed using the HPLC and GCMS. HPLC analysis revealed the presence of gallic acid (22.19µg/mg), catechin (29.17µg/mg), caffeic acid (9.17µg/mg), ferulic acid (0.94µg/mg), sinapic acid (1.91 µg/mg) and 4-hydroxy benzoic acid (43.86 µg/mg) in the aqueous extract. Phenolics fraction contained gallic acid (0.88 µg/mg), catechin (2.70µg/mg), caffeic acid (7.92µg/mg), ferulic acid (2.72µg/mg), benzoic acid (6.36µg/mg), p-coumaric acid (1.48µg/mg), quercetin (12.00µg/mg). Only caffeic acid (2.50µg/mg), ferulic acid (0.44µg/mg) and quercetin (8.50µg/mg) were detected in the flavonoid fraction. While GCMS analysis showed the presence of methylparaben; ethylparaben; benzoic acid; 4-hydroxy-2-methoxy-3,5,6-trimethyl-, methyl ester; 4-hydroxy-3-methoxy; phenol, 5-methoxy-2-(methoxymethyl)-; phenol, 5-methoxy-2, 3- dimethyl; and phenol, 2-(2-benzothiazolyl)-. This study is the first to reveal the identity of some phenolics components of the leaf of Telfairia occidentalis.
Asunto(s)
Antioxidantes/aislamiento & purificación , Cucurbitaceae/química , Flavonoides/aislamiento & purificación , Fenoles/aislamiento & purificación , Hojas de la Planta/química , Cromatografía Líquida de Alta Presión , Cromatografía de Gases y Espectrometría de MasasRESUMEN
Until recently hydrogen sulfide (H2S) was the least appreciated of the three gasotransmitters but now recognized as 3Y gaseous mediator after nitric oxide(NO) and carbon monoxide (CO). H2S regulates a number of physiological processes like vasorelaxation, prevention of inflammation, leukocyte adhesion, anti-prolifera- tive effects, anti-thrombotic effects, resistance to oxidative stress and protection against ischemia reperfusion injury (IRI). However, considerable amount of research is still needed to evaluate the mechanisms involved in the therapeutic effects of H2S in IRI such as its effects on nuclear factor-kappa B (NF-KB) concentration and intercellular adhesion molecule-1 (ICAM-1) expression in renal IRI and ARF (acute renal failure). More than a decade of good repute among researchers, H2S research has certain results that need to be clarified more such as whether H2S is pro-inflammatory or anti-inflammatory agent. Moreover, pathways adopted by H2S in the protein modification and its effects on cell signalling specially its effect on NF-KB in the process of inflamma- tion are not fully elucidated. H2S has delighted researchers and a great deal of information is being generated every year.The main purpose of the review is to provide an update on the development in the research of H2S in renal IRI due to uncertainty of the exact role of H2S on ICAM-1 expression and NF-KB concentration whether it inhibits or activates them.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Sulfuro de Hidrógeno/uso terapéutico , Molécula 1 de Adhesión Intercelular/metabolismo , Enfermedades Renales/tratamiento farmacológico , Riñón/efectos de los fármacos , FN-kappa B/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Humanos , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Transducción de Señal/efectos de los fármacosRESUMEN
In the family of gaseous transmitters, hydrogen sulfide (H2S) is considered as third member beside nitric oxide (NO) and carbon monoxide (CO), which can play physiological role in different organs. The present study was designed to elucidate the antioxidant and free radical scavenging potentials of L-arginnine (a source for endogenous production of NO in vivo) and NaHS (a source H2S) individually and in combination. Different assays like 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, percent inhibition of linoleic acid peroxidation and reducing power assays were used to evaluate the free radical scavenging capacity and antioxidant activity of L-arginine and NaHS. Furthermore, study was aimed to know the antioxidant potential of both compounds at their effective doses in human body, which is 56 µM for H2S and 1.2 g/mL for L-arginine. The study also aimed to clear whether either NaHS, L-arginine or the mixture of NaHS and L-arginine in vitio (in the form of new compounds) is responsible for their therapeutic action. Results showed that NaHS, L-arginine and combination of NaHS + L-arginine showed good radical scavenging activity i.e., 55.60%, 52.10% and 52.32%, respectively. Moreover, NaHS was found to have ability to inhibit linoleic acid peroxidation by 53.98% at effective dose while L-arginine did not show inhibition of linoleic acid peroxidation. Combination of NaHS + L-arginine showed 54.15% inhibition of linoleic acid peroxidation, which is similar to that of H2S. Reducing power of NaHS was 0.073 and L-arginine showed 0.037, combination of NaHS + L-arginine showed 0.063. It can be concluded that NaHS showed better antioxidant potential in vitio as compared to L-arginine and the antioxidant activity of the mixture of NaHS + L-arginine is closed to the antioxidant activity of NaHS, which reflects that NaHS is a dominant factor in combination mixture that is responsible for antioxidant activity.
Asunto(s)
Antioxidantes/farmacología , Arginina/farmacología , Depuradores de Radicales Libres/farmacología , Sulfuros/farmacología , HumanosRESUMEN
Left ventricular hypertrophy (LVH) is a compensatory mechanism in response to an increased work load on the heart. This study investigated the impact of chronic isoprenaline and caffeine (I/C model) administration on cardiac geometry, systemic hemodynamic and physiological data in rats as LVH develops. LVH was induced by administering isoprenaline (5 mg/kg s.c. every 72 h) and caffeine (62 mg/L) in drinking water for 14 days to Wistar Kyoto (WKY) rats. Mean arterial pressure (MAP), systolic blood pressure (SBP), heart weight, LV weight, LV chamber diameter and thickness of myocardium were observed as LVH indicators. MAP was significantly higher (142 ± 13 vs. 119 ± 2 mmHg, respectively) while heart rate (HR) in LVH was lower (314 ± 9 vs. 264 ± 18 BPM) compared to control WKY. Heart weight, LV weight and kidney weight were 31%, 38% and 7%, respectively, greater in the LVH group as compared to the control WKY (all p < 0.05).The myocardium thickness was 101% greater while LV chamber diameter was 44% smaller in the LVH group as compared to the control WKY (p < 0.05). The superoxide dismutase (SOD), glutathione reductase (GSH) and total antioxidant capacity (T-AOC) levels were significantly reduced while malonodialdehyde (MDA) level increased in LVH as compared to control WKY (all p < 0.05). In conclusion, isoprenaline and caffeine (I/C) induces LVH and cardiac hypertrophy with increases in blood pressure, fluid excretion and reduced renal hemodynamics. Prooxidant mechanism of the body and arterial stiffness are dominant in this disease model. This model of LVH is easily generated and associated with low mortality.
Asunto(s)
Cafeína/toxicidad , Hemodinámica/efectos de los fármacos , Hipertrofia Ventricular Izquierda/inducido químicamente , Isoproterenol/toxicidad , Riñón/efectos de los fármacos , Animales , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas WKY , Ratas WistarRESUMEN
This study investigated the role of α1D-adrenoceptor in the modulation of renal haemodynamics in rats with left ventricular hypertrophy (LVH). LVH was established in Wistar-Kyoto (WKY) rats with isoprenaline (5.0 mg · (kg body mass)(-1), by subcutaneous injection every 72 h) and caffeine (62 mg · L(-1) in drinking water, daily for 14 days). Renal vasoconstrictor responses were measured for noradrenaline (NA), phenylephrine (PE), and methoxamine (ME) before and immediately after low or high dose intrarenal infusions of BMY 7378, a selective α1D-adrenoceptor blocker. The rats with LVH had higher mean arterial blood pressure and circulating NA levels, but lower renal cortical blood perfusion compared with the control group (all P < 0.05). In the LVH group, the magnitude of the renal vasoconstrictor response to ME was blunted, but not the response to NA or PE (P < 0.05), compared with the control group (LVH vs. C, 38% vs. 50%). The magnitude of the drop in the vasoconstrictor responses to NA, PE, and ME in the presence of a higher dose of BMY 7378 was significantly greater in the LVH group compared with the control group (LVH vs. C, 45% vs. 25% for NA, 52% vs. 33% for PE, 66% vs. 53% for ME, all P < 0.05). These findings indicate an impaired renal vasoconstrictor response to adrenergic agonists during LVH. In addition, the α1D-adrenoceptor subtype plays a key role in the modulation of vascular responses in this diseased state.
Asunto(s)
Cafeína , Hipertrofia Ventricular Izquierda/metabolismo , Isoproterenol , Riñón/irrigación sanguínea , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas de Receptores Adrenérgicos alfa 1/farmacología , Animales , Presión Arterial/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/fisiopatología , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Metoxamina/farmacología , Norepinefrina/sangre , Norepinefrina/farmacología , Fenilefrina/farmacología , Piperazinas/farmacología , Ratas Endogámicas WKY , Flujo Sanguíneo Regional , Vasoconstrictores/farmacologíaRESUMEN
Oxidative stress and suppressed H2S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H2S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n=6) were treated for 4 weeks either as controls or received NaHS (SHR+NaHS), tempol (SHR+Tempol), or NaHS plus tempol (SHR+NaHS +Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0 ± 2 vs. 100.0 ± 3 mmHg), lower plasma and urinary H2S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p<0.05). Treatment either with NaHS or with tempol alone decreased blood pressure and oxidative stress and improved renal hemodynamic and excretory function compared to untreated SHR. Combined NaHS and tempol therapy in SHRs caused larger decreases in blood pressure (â¼20-22% vs. â¼11-15% and â¼10-14%), increases in creatinine clearance, urinary sodium excretion and fractional sodium excretion and up-regulated the antioxidant status compared to each agent alone (all p<0.05). These findings demonstrated that H2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.
Asunto(s)
Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Óxidos N-Cíclicos/farmacología , Sulfuro de Hidrógeno/farmacología , Hipertensión/fisiopatología , Riñón/metabolismo , Natriuréticos/farmacología , Vasodilatadores/farmacología , Animales , Peso Corporal/efectos de los fármacos , Modelos Animales de Enfermedad , Ingestión de Líquidos/efectos de los fármacos , Hipertensión Esencial , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Riñón/efectos de los fármacos , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Circulación Renal/efectos de los fármacos , Marcadores de Spin , Urinálisis , Micción/efectos de los fármacosRESUMEN
During the COVID-19 pandemic, educational institutions confronted the possibility of complete closure and took countermeasures by adapting e-learning platforms. The present cross-sectional study quantified the impact of the pandemic on medical education using a validated and reliable tool. The tool was used to explore the perceptions of 270 healthcare students about e-learning in comparison to traditional learning systems. Inferential statistics were employed using Pearson's chi-squared test. It was found that e-learning was advantageous because of its location flexibility (46.1%) and the ease of access to study materials (46.5%). However, in-person learning was found to lead to an increase in knowledge (44.9%), clinical skills (52.7%), and social competencies (52.7%). The study concluded that while e-learning offers flexibility, traditional face-to-face teaching is deemed more effective for skill development and social interaction. Hence, e-learning should complement rather than replace traditional methods due to limitations in replicating clinical environments.
RESUMEN
This study investigated the effects of tempol, a superoxide dismutase (SOD) mimetic and L-NAME, a nitric oxide (NO) synthase inhibitor on the renal function and hemodynamics in cyclosporine A (CsA) induced renal insufficiency rats. Male Sprague-Dawley rats were treated with either vehicle (C), tempol (T, 1 mmol/L in drinking fluid), L-NAME (L, 1 mmol/L in drinking fluid), CsA (Cs, 25 mg/kg/day via gavage), CsA plus tempol (TCs), CsA plus L-NAME (LCs) or CsA plus a combination of tempol and L-NAME (TLCs) for 21 consecutive days. At the end of treatment regimen, the renal responses to noradrenaline (NA), phenylephrine (PE), methoxamine and angiotensin II (Ang II) were determined. Cs and LCs rats had lower creatinine clearance (0.7 ± 0.1 and 0.6 ± 0.5 vs. 1.3 ± 0.2 mL/min/kg) and fractional excretion of sodium (0.12 ± 0.02 and 0.17 ± 0.01 vs. 0.67 ± 0.04%) but higher systolic blood pressure (145 ± 2 and 178 ± 4 vs. 116 ± 2) compared to the control (all p < 0.05), respectively. Tempol treatment in TCs or TLCs prevented the increase in blood pressure and improved creatinine clearance and sodium excretion compared to untreated Cs. The renal vasoconstriction in Cs or LCs to NA, PE and Ang II were lower than control by â¼35-48% (all p < 0.05). In TCs or TLCs, there was enhanced renal vasoconstriction to all agonist by â¼39-114% compared to Cs. SOD is important to counterbalance the hypertensive effect of a defective NO system and to allow the normal vasoconstrictor response of the renal vasculature to adrenergic agonists and Ang II in a model of CsA-induced renal insufficiency.
Asunto(s)
Óxidos N-Cíclicos/farmacología , Ciclosporina/farmacología , Hemodinámica/efectos de los fármacos , Hipertensión/prevención & control , Capacidad de Concentración Renal/efectos de los fármacos , Insuficiencia Renal , Animales , Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Modelos Animales de Enfermedad , Hipertensión/etiología , Hipertensión/fisiopatología , Riñón/irrigación sanguínea , Masculino , NG-Nitroarginina Metil Éster/administración & dosificación , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Ratas , Ratas Sprague-Dawley , Flujo Sanguíneo Regional/efectos de los fármacos , Insuficiencia Renal/inducido químicamente , Insuficiencia Renal/fisiopatología , Marcadores de Spin , Superóxido Dismutasa/administración & dosificación , Superóxido Dismutasa/metabolismoRESUMEN
The present study explored the hypothesis that a prolonged 8 weeks exposure to a high fructose intake suppresses adrenergic and angiotensin II (Ang II)-mediated vasoconstriction and is associated with a higher contribution of α1D-adrenoceptors. A total of thirty-two Sprague-Dawley rats received either 20 % fructose solution (FFR) or tap water (control, C) to drink ad libitum for 8 weeks. Metabolic and haemodynamic parameters were assessed weekly. The renal cortical vasoconstrictor responses to noradrenaline (NA), phenylephrine (PE), methoxamine (ME) and Ang II were determined in the presence and absence of BMY7378 (α1D-adrenoceptor antagonist). FFR had increased blood pressure, plasma levels of glucose, TAG and insulin. FFR expressed reduced renal vascular responses to adrenergic agonists and Ang II (NA: 50 %, PE: 50 %, ME, 65 %, Ang II: 54 %). Furthermore in the C group, the magnitude of the renal cortical vasoconstriction to all agonists was blunted in the presence of the low or high dose of BMY7378 (NA: 30 and 31 %, PE: 23 and 33 %, ME: 19 and 44 %, Ang II: 53 and 77 %), respectively, while in the FFR, vasoconstriction was enhanced to adrenergic agonists and reduced to Ang II (NA: 8 and 83 %, PE: 55 %, ME, 2 and 177 %, Ang II: 61 and 31 %). Chronic high fructose intake blunts vascular sensitivity to adrenergic agonists and Ang II. Moreover, blocking of the α1D-adrenoceptor subtype results in enhancement of renal vasoconstriction to adrenergic agonists, suggesting an inhibitory action of α1D-adrenoceptors in the FFR. α1D-Adrenoceptors buffer the AT1-receptor response in the renal vasculature of normal rats and fructose feeding suppressed this interaction.
Asunto(s)
Carbohidratos de la Dieta/efectos adversos , Fructosa/efectos adversos , Hiperinsulinismo/fisiopatología , Hipertensión/etiología , Riñón/irrigación sanguínea , Receptores Adrenérgicos alfa 1/metabolismo , Circulación Renal , Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Antagonistas Adrenérgicos alfa/farmacología , Angiotensina II/metabolismo , Animales , Carbohidratos de la Dieta/administración & dosificación , Fructosa/administración & dosificación , Hemodinámica/efectos de los fármacos , Hiperglucemia/sangre , Hiperglucemia/etiología , Hiperinsulinismo/etiología , Hiperinsulinismo/metabolismo , Hipertensión/metabolismo , Hipertrigliceridemia/sangre , Hipertrigliceridemia/etiología , Riñón/efectos de los fármacos , Masculino , Norepinefrina/metabolismo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Adrenérgicos alfa 1/química , Receptores de Angiotensina/química , Receptores de Angiotensina/metabolismo , Circulación Renal/efectos de los fármacos , Vasoconstrictores/farmacologíaRESUMEN
α(1D)-adrenoceptors are involved in the genesis/maintenance of hypertension in spontaneously hypertensive rats (SHR). This study aims to investigate the role of α(1D)-adrenoceptors in the antinatriuretic and antidiuretic responses in SHR subjected to high sodium (SHRHNa) and normal sodium (SHRNNa) intake for six weeks. Renal inulin clearance study was performed in which the antinatriuretic and antidiuretic responses to phenylephrine were examined in the presence and absence of α(1D)-adrenoceptors blocker BMY7378. Data, mean±S.E.M. were subjected to ANOVA with significance at p<0.05. Results show that feeding SHR for six weeks with high salt did not cause any change in blood pressure. SHRHNa had higher (all p<0.05) urine flow rate (UFR), fractional and absolute excretion of sodium (FE(Na) and U(Na)V) compared to SHRNNa. Phenylephrine infusion produced significant reduction in UFR, FE(Na) and U(Na)V in both SHRHNa and SHRNNa. The antidiuretic and antinatriuretic responses to phenylephrine in both groups were attenuated in the presence of BMY7378. Moreover, the antidiuretic and antinatriuretic responses to phenylephrine and BMY7378 were independent on any significant changes in renal and glomerular hemodynamics in both groups. Thus we conclude that high sodium intake did not bring any further increase in blood pressure of SHR, however, it results in exaggerated natriuresis and diuresis in SHRHNa. Irrespective of dietary sodium changes, α1-adrenoceptors are involved in mediating the antinatriuretic and antidiuretic responses to phenylephrine in SHR. Further, high sodium intake did not significantly influence the functionality of α(1D)-adrenoceptors in mediating the adrenergically induced antinatriuresis and antidiuresis.
Asunto(s)
Diuresis , Túbulos Renales/metabolismo , Natriuresis , Receptores Adrenérgicos alfa 1/fisiología , Sodio en la Dieta/administración & dosificación , Sodio/metabolismo , Animales , Presión Sanguínea , Diuresis/efectos de los fármacos , Natriuresis/efectos de los fármacos , Fenilefrina/farmacología , Ratas , Ratas Endogámicas SHRRESUMEN
BACKGROUND: It is well established that renal sympathetic nerves are primarily involved in renal sodium and water regulation. However, the relationship between renal sympathetic nerve activity (RSNA) and renal potassium handling is not extensively known. The present study was performed to investigate the role of the renal sympathetic nervous system in the regulation of tubular potassium reabsorption and secretion. METHODS: Male Sprague Dawley (SD) rats (each group, n=6) were fasted overnight, anesthetized with pentobarbital sodium (60 mg/kg intraperitoneal), denervated by application of phenol to the left renal artery and maintained on an intravenous infusion of saline for 2 hours. During this period, 6 urine and plasma samples were collected at 20-minute intervals to study kidney function parameters. RESULTS: In denervated rats, there were significantly higher (all p<0.05 vs. innervated control) urine flow rate (UFR), glomerular filtration rate (GFR), absolute sodium excretion (U(Na)V), fractional sodium excretion (FE(N)a), absolute potassium excretion (U(K)V), fractional potassium excretion (FE(K)) and urinary sodium to urinary potassium ratio (U(Na)/U(K)). No appreciable differences were seen in the mean arterial pressure (MAP) and plasma sodium (P(Na)) between denervated and innervated SD rats. However, plasma potassium (P(K)) levels were significantly lower (p<0.05) in denervated rats as compared with innervated counterparts. CONCLUSIONS: There is a possible involvement of renal nerves in the regulation of renal potassium handling. This effect is largely attributable to a direct action of renal sympathetic nerves on the renal tubular segments.
Asunto(s)
Riñón/inervación , Riñón/metabolismo , Potasio/metabolismo , Sistema Nervioso Simpático/fisiología , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
AIM: This study investigated the impact of hypertension combined with diabetic nephropathy on rat renal alpha(1)-adrenoceptor subtype composition. METHODS: In streptozotocin-induced diabetic spontaneously hypertensive rats (SHR), diabetic nephropathy developed as reflected by increased kidney index, plasma creatinine, albumin excretion, creatinine clearance and fractional excretion of Na(+) (all p < 0.05). Renal vasoconstrictions caused by electrical stimulation of renal nerves and intrarenally administered noradrenaline (alpha-adrenoceptor agonist), phenylephrine (alpha(1)-adrenoceptor agonist) and methoxamine (alpha(1A)-adrenoceptor agonist) were determined in the presence and absence of intrarenally administered amlodipine (Ca(2+) channel blocker), 5-methylurapidil (alpha(1A)-adrenoceptor antagonist), chloroethylclonidine (alpha(1B)-adrenoceptor antagonist) and BMY 7378 (alpha(1D)-adrenoceptor antagonist). RESULTS: In diabetic nephropathy SHR, there was a significant (all p < 0.05) attenuation of all adrenergically induced vasoconstrictor responses in the antagonists, except chloroethylclonidine, which caused a significant (all p < 0.05) enhancement of the responses. CONCLUSION: The data demonstrated that there was a functional coexistence of alpha(1A)- and alpha(1D)-adrenoceptors in the renal vasculature of SHR irrespective of the presence of diabetic nephropathy. However, there was a minor contribution of pre-synaptic alpha-adrenoceptors to the adrenergically mediated vasoconstrictor responses in the diabetic nephropathy SHR.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Nefropatías Diabéticas/metabolismo , Hipertensión/metabolismo , Receptores Adrenérgicos alfa 1/clasificación , Receptores Adrenérgicos alfa 1/metabolismo , Antagonistas Adrenérgicos/farmacología , Amlodipino/farmacología , Animales , Diabetes Mellitus Experimental/inducido químicamente , Nefropatías Diabéticas/fisiopatología , Modelos Animales de Enfermedad , Estimulación Eléctrica , Riñón , Masculino , Metoxamina/farmacología , Norepinefrina/farmacología , Fenilefrina/farmacología , Ratas , Ratas Endogámicas SHR , Estreptozocina , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiología , Vasoconstrictores/farmacología , Vasodilatadores/farmacologíaRESUMEN
Hydrogen sulphide (H2S) is an emerging molecule in many cardiovascular complications but its role in left ventricular hypertrophy (LVH) is unknown. The present study explored the effect of exogenous H2S administration in the regression of LVH by modulating oxidative stress, arterial stiffness and expression of cystathione γ lyase (CSE) in the myocardium. Animals were divided into four groups: Control, LVH, Control-H2S and LVH-H2S. LVH was induced by administering isoprenaline (5mg/kg, every 72 hours, S/C) and caffeine in drinking water (62mg/L) for 2 weeks. Intraperitoneal NaHS, 56µM/kg/day for 5 weeks, was given as an H2S donor. Myocardial expression of Cystathione γ lyase (CSE) mRNA was quantified using real time polymerase chain reaction (qPCR).There was a 3 fold reduction in the expression of myocardial CSE mRNA in LVH but it was up regulated by 7 and 4 fold in the Control-H2S and LVH-H2S myocardium, respectively. Systolic blood pressure, mean arterial pressure, pulse wave velocity were reduced (all P<0.05) in LVH-H2S when compared to the LVH group. Heart, LV weight, myocardial thickness were reduced while LV internal diameter was increased (all P<0.05) in the LVH-H2S when compared to the LVH group. Exogenous administration of H2S in LVH increased superoxide dismutase, glutathione and total antioxidant capacity but significantly reduced (all P<0.05) plasma malanodialdehyde in the LVH-H2S compared to the LVH group. The renal cortical blood perfusion increased by 40% in LVH-H2S as compared to the LVH group. Exogenous administration of H2S suppressed the progression of LVH which was associated with an up regulation of myocardial CSE mRNA/ H2S and a reduction in pulse wave velocity with a blunting of systemic hemodynamic. This CSE/H2S pathway exhibits an antihypertrophic role by antagonizing the hypertrophic actions of angiotensin II(Ang II) and noradrenaline (NA) but attenuates oxidative stress and improves pulse wave velocity which helps to suppress LVH. Exogenous administration of H2S augmented the reduced renal cortical blood perfusion in the LVH state.
Asunto(s)
Cafeína/efectos adversos , Cistationina gamma-Liasa/biosíntesis , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Sulfuro de Hidrógeno/metabolismo , Hipertrofia Ventricular Izquierda , Isoproterenol/efectos adversos , Miocardio/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Animales , Cafeína/farmacología , Hipertrofia Ventricular Izquierda/inducido químicamente , Hipertrofia Ventricular Izquierda/metabolismo , Hipertrofia Ventricular Izquierda/patología , Isoproterenol/farmacología , Masculino , Miocardio/patología , Ratas , Ratas Endogámicas WKYRESUMEN
In the family of gas transmitters, hydrogen sulfide (H2S) is yet not adequately researched. Known for its rotten egg smell and adverse effects on the brain, lungs, and kidneys for more than 300 years, the vasorelaxant effects of H2S on blood vessel was first observed in 1997. Since then, research continued to explore the possible therapeutic effects of H2S in hypertension, inflammation, pancreatitis, different types of shock, diabetes, and heart failure. However, a considerable amount of efforts are yet needed to elucidate the mechanisms involved in the therapeutic effects of H2S, such as nitric oxide-dependent or independent vasodilation in hypertension and regression of left ventricular hypertrophy. More than a decade of good repute among researchers, H2S research has certain results that need to be clarified or reevaluated. H2S produces its response by multiple modes of action, such as opening the ATP-sensitive potassium channel, angiotensin-converting enzyme inhibition, and calcium channel blockade. H2S is endogenously produced from two sulfur-containing amino acids L-cysteine and L-methionine by the two enzymes cystathionine γ lyase and cystathionine ß synthase. Recently, the third enzyme, 3-mercaptopyruvate sulfur transferase, along with cysteine aminotransferase, which is similar to aspartate aminotransferase, has been found to produce H2S in the brain. The H2S has interested researchers, and a great deal of information is being generated every year. This review aims to provide an update on the developments in the research of H2S in hypertension amid the ambiguity in defining the exact role of H2S in hypertension because of insufficient number of research results on this area. This critical review on the role of H2S in hypertension will clarify the gray areas and highlight its future prospects.
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Gasotransmisores/fisiología , Sulfuro de Hidrógeno/metabolismo , Hipertensión/metabolismo , Gasotransmisores/biosíntesis , Gasotransmisores/metabolismo , Humanos , Vasodilatación/fisiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Citrullus colocynthis (L.) Schrad is a valuable cucurbit plant, widely distributed in the desert areas of the world. Citrullus colocynthis fruits are usually recognized for its wide range of medicinal uses as well as pharmaceutical and nutraceutical potential. This review aims to appraise the published information on the ethnobotanical knowledge, phytochemistry, ethnopharmacology, nutraceutical potential and safety studies of Citrullus colocynthis (bitter apple) fruit, with critical analysis on the gaps and potential for future studies. MATERIAL AND METHODS: A literature survey was performed by searching the scientific databases including PubMed, Scopus, SciFinder, Google Scholar, Web of Science, ACS as well as published books. RESULTS: The plant has been reported to possess a wide range of traditional medicinal uses including in diabetes, leprosy, common cold, cough, asthma, bronchitis, jaundice, joint pain, cancer, toothache, wound, mastitis, and in gastrointestinal disorders such as indigestion, constipation, dysentery, gastroenteritis, colic pain and different microbial infections. Several bioactive chemical constituents from fruits were recorded, such as, glycosides, flavonoids, alkaloids, fatty acids and essential oils. The isolation and identification of curcurbitacins A, B, C, D, E, I, J, K, and L and Colocynthosides A, and B were also reported. The fruit of Citrullus colocynthis has been studied extensively for its wide range of biological activities, which include antioxidant, cytotoxic, antidiabetic, antilipidemic, insecticide, antimicrobial and anti-inflammatory. The plant was also shown to be rich in nutritional value with high protein contents and important minerals as well as edible quality of seed oil. CONCLUSION: It is evident from the literature that Citrullus colocynthis possesses a wide range of medicinal uses and has been well studied for its antidiabetic, anticancer, antioxidant, antimicrobial and anti-inflammatory activities, while its therapeutic potential for gut, airways and cardiovascular disorders remains to be explored. Critical analysis revealed that the plant has the huge potential for pharmaceutical and nutraceutical application, with some indications for the presence of synergistic and /or side effects neutralizing combinations of activities.
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Citrullus colocynthis/química , Medicina Tradicional/métodos , Extractos Vegetales/farmacología , Animales , Etnofarmacología , Frutas , Humanos , Extractos Vegetales/efectos adversosRESUMEN
The current study evaluates the impact of high saturated fat feeding in rat model of experimental nephrotoxicity induced by gentamicin. Sprague-Dawley rats weighing 200 g were randomized into four groups; the first one received the standard rodents chow for 8 weeks and was treated as control, the second group (HFD)received an experimental high fat diet rich in palm kernel oil (40% of Calories as fat) for the same period. The third group (HFDG) was given 80 mg/kg (body weight)/day gentamicin sulphate intraperitoneally during the last 24 days of the feeding period while the fourth group was given gentamicin as above along with the standard rodents chow. Renal function was assessed through measuring serum creatinine, creatinine clearance and absolute and fractional excretion of both sodium and potassium. At the end, rats underwent a surgical procedure for blood pressure measurement. Renal function study showed a stronger nephrotoxicity for HFDG group. Hypertension was observed in HFD group while the pressure declined after gentamicin co-administration. Overall, changing the feeding behavior toward using more SAFFAs for rats injected with gentamicin promotes the progression of renal failure.
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Antibacterianos/toxicidad , Ácidos Grasos no Esterificados/administración & dosificación , Ácidos Grasos/administración & dosificación , Gentamicinas/toxicidad , Insuficiencia Renal/inducido químicamente , Animales , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Riñón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal/patologíaRESUMEN
BACKGROUND: This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats. METHODS: Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME). RESULTS: In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists. CONCLUSIONS: Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats.
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Agonistas de Receptores Adrenérgicos alfa 1/farmacología , Angiotensina II/farmacología , Riñón/inervación , Sistema Nervioso Simpático/fisiología , Vasoconstricción/efectos de los fármacos , Animales , Presión Sanguínea/efectos de los fármacos , Masculino , Metoxamina/farmacología , Norepinefrina/farmacología , Ratas , Ratas Endogámicas WKY , Receptor de Angiotensina Tipo 1/fisiología , Receptores Adrenérgicos alfa 1/fisiología , Circulación Renal/efectos de los fármacosRESUMEN
Cardiovascular complications are consistently observed in diabetic patients across all age groups. The objective of the present study was to investigate the effect of aqueous extract of the fruit pulp of Hylocereus undatus (DFE) on aortic stiffness and oxidative stress in streptozotocin (STZ)-induced diabetes in rats. Twenty-four male, Sprague-Dawley rats were randomized into four groups: I (control), II (diabetic), III (DFE, 250 mg/kg) and IV (DFE 500 mg/kg). Diabetes was induced in groups II, III and IV by intraperitoneal (i.p.) injection of STZ (40 mg/kg). After confirmation of diabetes, group III and IV received DFE for 5 weeks. Pulse wave velocity (PWV) was used as a marker of aortic stiffness and was determined at the end of 5 weeks. DFE significantly decreased (P < 0.05) the fasting blood glucose levels in diabetic rats, but not to normal levels. Systolic blood pressure, pulse pressure and PWV were significantly increased (P < 0.05) in diabetic rats at the end of 5 weeks in comparison with control group. DFE treatment significantly decreased (P < 0.05) these elevations. Oxidative damage was observed in group II after 5 weeks. Plasma malondialdehyde levels significantly decreased (P < 0.05), while superoxide dismutase and total antioxidant capacity significantly increased (P < 0.05) with DFE treatment in comparison with group II. These data demonstrate that DFE treatment was effective in controlling oxidative damage and decreasing the aortic stiffness measured by PWV in STZ-induced diabetes in rats.