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Despite constant achievements in treatment, acute kidney injury (AKI) remains a significant public health problem and a cause of mortality in the human population. In developed countries, AKI is a significant and frequent hospital complication, especially among patients admitted to intensive care units, where mortality rates can reach up to 50%. In addition, AKI has been implicated as an independent risk factor for the development of chronic kidney disease. Hyperbaric oxygenation (HBO) has been used as a primary or adjunctive therapy for the past 50 years, both in experimental and clinical studies. HBO is a treatment in which the patient is occasionally exposed to 100% oxygen at a pressure greater than atmospheric pressure at sea level. However, despite decades of extensive research, the potentially beneficial effects of this therapeutic approach are still not fully understood, although many potential mechanisms have been proposed, such as antioxidative, anti-inflammatory, anti-apoptotic, etc. Furthermore, the low cost and insignificant adverse events make HBO a potentially important strategy in the prevention and treatment of different diseases. Considering all of this, this review highlights the potential role of HBO in maintaining cellular homeostasis disrupted due to AKI, caused in different experimental models.
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Lesión Renal Aguda , Oxigenoterapia Hiperbárica , Oxigenoterapia Hiperbárica/métodos , Lesión Renal Aguda/terapia , Humanos , AnimalesRESUMEN
The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.
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Lesión Renal Aguda , Oxigenoterapia Hiperbárica , Daño por Reperfusión , Animales , Ratas , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Antioxidantes , Biomarcadores , Daño del ADN , Riñón , FN-kappa B , Estrés Oxidativo , Oxígeno , Ratas Endogámicas SHRRESUMEN
Cardiovascular diseases (CVDs) are a group of diseases with a very high rate of morbidity and mortality. The clinical presentation of CVDs can vary from asymptomatic to classic symptoms such as chest pain in patients with myocardial infarction. Current therapeutics for CVDs mainly target disease symptoms. The most common CVDs are coronary artery disease, acute myocardial infarction, atrial fibrillation, chronic heart failure, arterial hypertension, and valvular heart disease. In their treatment, conventional therapies and pharmacological therapies are used. However, the use of herbal medicines in the therapy of these diseases has also been reported in the literature, resulting in a need for critical evaluation of advances related to their use. Therefore, we carried out a narrative review of pharmacological and herbal therapeutic effects reported for these diseases. Data for this comprehensive review were obtained from electronic databases such as MedLine, PubMed, Web of Science, Scopus, and Google Scholar. Conventional therapy requires an individual approach to the patients, as when patients do not respond well, this often causes allergic effects or various other unwanted effects. Nowadays, medicinal plants as therapeutics are frequently used in different parts of the world. Preclinical/clinical pharmacology studies have confirmed that some bioactive compounds may have beneficial therapeutic effects in some common CVDs. The natural products analyzed in this review are promising phytochemicals for adjuvant and complementary drug candidates in CVDs pharmacotherapy, and some of them have already been approved by the FDA. There are insufficient clinical studies to compare the effectiveness of natural products compared to approved therapeutics for the treatment of CVDs. Further long-term studies are needed to accelerate the potential of using natural products for these diseases. Despite this undoubted beneficence on CVDs, there are no strong breakthroughs supporting the implementation of natural products in clinical practice. Nevertheless, they are promising agents in the supplementation and co-therapy of CVDs.
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Ischemia-reperfusion injury (IRI) is a frequent cause of AKI, resulting in vasoconstriction, cellular dysfunction, inflammation and the induction of oxidative stress. DNA damage, including physical DNA strand breaks, is also a potential consequence of renal IRI. The histone H2A variants, primary H2AX and H2AZ participate in DNA damage response pathways to promote genome stability. The aim of this study was to evaluate the immunohistochemical pattern of histone H2A variants' (H2AX, γH2AX(S139), H2AXY142ph and H2AZ) expression in an experimental model of ischemia-reperfusion-induced acute kidney injury in spontaneously hypertensive rats. Comparing the immunohistochemical nuclear expression of γH2AX(S139) and H2AXY142ph in AKI, we observed that there is an inverse ratio of these two histone H2AX variants. If we follow different regions from the subcapsular structures to the medulla, there is an increasing extent gradient in the nuclear expression of H2AXY142ph, accompanied by a decreasing nuclear expression of γH2AX. In addition, we observed that different structures dominated when γH2AX and H2AXY142ph expression levels were compared. γH2AX was expressed only in the proximal tubule, with the exception of when they were dilated. In the medulla, H2AXY142ph is predominantly expressed in the loop of Henle and the collecting ducts. Our results show moderate sporadic nuclear H2AZ expression mainly in the cells of the distal tubules and the collecting ducts that were surrounded by dilated tubules with PAS (periodic acid-Schiff stain)-positive casts. These findings may indicate the degree of DNA damage, followed by postischemic AKI, with potential clinical and prognostic implications regarding this condition.
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Lesión Renal Aguda , Daño por Reperfusión , Ratas , Animales , Histonas/metabolismo , Riñón/metabolismo , Lesión Renal Aguda/genética , Lesión Renal Aguda/metabolismo , Daño por Reperfusión/complicaciones , Daño por Reperfusión/genética , Daño por Reperfusión/metabolismo , Reperfusión , Isquemia/metabolismo , Modelos TeóricosRESUMEN
BACKGROUND: The main cause of death among patients with malignant hypertension is a kidney failure. The promising field in essential and malignant hypertension therapy could be centered on the amelioration of oxidative stress using antioxidant molecules like resveratrol. Resveratrol is a potent antioxidative agent naturally occurred in many plants that possess health-promoting properties. METHODS: In the present study, we investigated the therapeutic potential of resveratrol, a polyphenol with anti-oxidative activity, in NG-L-Arginine Methyl Ester (L-NAME) treated spontaneously hypertensive rats (SHR) - malignantly hypertensive rats (MHR). RESULTS: Resveratrol significantly improves oxidative damages by modulation of antioxidant enzymes and suppression of prooxidant factors in the kidney tissue of MHR. Enhanced antioxidant defense in the kidney improves renal function and ameliorates the morphological changes in this target organ. Besides, protective properties of resveratrol are followed by the restoration of the nitrogen oxide (NO) pathway. 4) Conclusion: Antioxidant therapy with resveratrol could represent promising therapeutical approach in hypertension, especially malignant, against kidney damage.
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Hipertensión Maligna , Hipertensión , Ratas , Animales , Antioxidantes/metabolismo , Resveratrol/farmacología , Resveratrol/uso terapéutico , Óxido Nítrico/metabolismo , Hipertensión Maligna/tratamiento farmacológico , Hipertensión Maligna/metabolismo , Hipertensión Maligna/patología , Disponibilidad Biológica , Hipertensión/metabolismo , Riñón/patología , Ratas Endogámicas SHR , Estrés Oxidativo , NG-Nitroarginina Metil Éster/metabolismo , Presión SanguíneaRESUMEN
The objective of this study was to formulate extended-release mucoadhesive buccal tablets of propranolol hydrochloride in order to provide a prolonged absorption of propranolol hydrochloride from the buccal mucosa and to reduce presystemic metabolism and thus provide a better therapeutic effect. Besides, the aim was to perform comparative in vivo pharmacokinetic and hemodynamic studies of the developed extended-release (ER) propranolol hydrochloride 10 mg mucoadhesive buccal tablets and commercial immediate-release (IR) propranolol hydrochloride 10 mg tablets in spontaneously hypertensive rats. Formulation with 15% polyethylene oxide showed the highest degree of propranolol hydrochloride permeation, satisfactory mucoadhesiveness, and extended-release of propranolol hydrochloride, thus it was selected for further in vivo study. The pharmacokinetic study in rats showed the superiority of ER mucoadhesive buccal tablets over IR tablets in terms of propranolol hydrochloride absorption extent (AUC values: 70.32 ± 19.56 versus 31.69 ± 6.97 µg·h/mL), although lower maximum plasma propranolol hydrochloride concentration (Cmax) was achieved. However, no statistically significant difference was observed in Cmax between these treatments. The hemodynamic study showed that ER mucoadhesive buccal tablets provide a more pronounced decrease primarily in heart rate, but also in systolic and diastolic arterial pressure, as well as a longer heart rate reduction compared to IR tablets.
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Mucosa Bucal , Propranolol , Adhesividad , Administración Bucal , Animales , Hipertensión Esencial , Ratas , ComprimidosRESUMEN
Oxidative damage to protein and lipid macromolecules in target organs in hypertension has been recognized as a major factor contributing to cardiovascular, cerebrovascular, and renal diseases. Data on protein and lipid oxidative damage in spontaneously hypertensive rats are numerous, but there is no information on DNA damage in tissues measured by comet assay. The aim of this study was to determine the baseline damage to DNA, protein, and lipid macromolecules in different organs of spontaneously hypertensive rats. Markers of lipid peroxidation, protein oxidation, and DNA damage were measured in blood, heart, kidney, and liver of 24-week-old spontaneously hypertensive rats. Plasma prooxidant and antioxidant status were determined as well. Age-matched normotensive Wistar rats were used as control. A rise in markers of lipid peroxidation and protein oxidation, malondialdehyde, and advanced oxidation protein products, was detected in all tissues of spontaneously hypertensive rats, with particularly high values in the liver. DNA damage, measured by the comet assay, was significantly higher in all the studied tissues of spontaneously hypertensive rats compared to normotensive control, with more severe damage in the cardiac and renal cells. Significant depletion of the plasma antioxidant barrier in spontaneously hypertensive rats was also observed. This study showed increased damage to all macromolecules in all studied samples of spontaneously hypertensive rats in comparison with control Wistar rats.
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Hipertensión , Estrés Oxidativo , Animales , Presión Sanguínea , Masculino , Ratas , Ratas WistarRESUMEN
Oxidative stress has been considered as a central aggravating factor in the development of postischemic acute kidney injury (AKI). The aim of this study was to perform the immunohistochemical analysis of 4-hydroxynonenal (4-HNE), neutrophil gelatinase-associated lipocalin (NGAL), and heme oxygenase-1 (HO-1) tissue expression after apocynin (APO) treatment and hyperbaric oxygenation (HBO) preconditioning, applied as single or combined protocol, in postischemic acute kidney injury induced in spontaneously hypertensive rats (SHR). Twenty-four hours before AKI induction, HBO preconditioning was carried out by exposing to pure oxygen (2.026 bar) twice a day, for 60 min in two consecutive days. Acute kidney injury was induced by removal of the right kidney while the left renal artery was occluded for 45 min by atraumatic clamp. Apocynin was applied in a dose of 40 mg/kg body weight, intravenously, 5 min before reperfusion. We showed increased 4-HNE renal expression in postischemic AKI compared to Sham-operated (SHAM) group. Apocynin treatment, with or without HBO preconditioning, improved creatinine and phosphate clearances, in postischemic AKI. This improvement in renal function was accompanied with decreased 4-HNE, while HO-1 kidney expression restored close to the control group level. NGAL renal expression was also decreased after apocynin treatment, and HBO preconditioning, with or without APO treatment. Considering our results, we can say that 4-HNE tissue expression can be used as a marker of oxidative stress in postischemic AKI. On the other hand, apocynin treatment and HBO preconditioning reduced oxidative damage, and this protective effect might be expected even in experimental hypertensive condition.
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Lifestyle modifications such as increase in high-fat food consumption importantly increases the risks for cardiovascular disease. The principal objective of this study is to analyze effects of different high fat diet (HFD) sources on haemodynamic parameters, lipid and oxidative profile, myeloperoxidase activity, and markers of inflammation (IL-6/pentraxin-3). HFD containing 20% of fat, provided by lard (saturated) or soybean oil (unsaturated), as well as control diet were administering to three groups (L, SO and C). Food efficiency ratio and plasma lipids were significantly elevated in both HFD groups. However, only SO group showed an increase in systolic arterial pressure, oxidative stress index, myeloperoxidase activity, liver lipids as well as markers of inflammation: IL-6 and pentraxin-3 (PTX3). In summary, these results indicate inflammogenic potential of excessive soybean oil consumption in triggering liver damage.
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Ácidos Grasos Insaturados/administración & dosificación , Inflamación/inducido químicamente , Inflamación/metabolismo , Estrés Oxidativo/fisiología , Animales , Biomarcadores/metabolismo , Proteína C-Reactiva/metabolismo , Dieta Alta en Grasa/efectos adversos , Grasas de la Dieta/efectos adversos , Interleucina-6/metabolismo , Hígado/metabolismo , Masculino , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Componente Amiloide P Sérico/metabolismo , Aceite de Soja/efectos adversosRESUMEN
Hypertension is one of the most prevalent and powerful contributors of cardiovascular diseases. Malignant hypertension is a relatively rare but extremely severe form of hypertension accompanied with heart, brain, and renal impairment. Resveratrol, a recently described grape-derived, polyphenolic antioxidant molecule, has been proposed as an effective agent in the prevention of cardiovascular diseases. This study was designed to examine chronic resveratrol administration on blood pressure, oxidative stress, and inflammation, with special emphasis on cardiac structure and function in two models of experimental hypertension. The experiments were performed in spontaneously (SHRs) and malignantly hypertensive rats (MHRs). The chronic administration of resveratrol significantly decreased blood pressure in both spontaneously and malignant hypertensive animals. The resveratrol treatment ameliorated morphological changes in the heart tissue. The immunohistochemistry of the heart tissue after resveratrol treatment showed that both TGF-ß and Bax were not present in the myocytes of SHRs and were present mainly in the myocytes of MHRs. Resveratrol suppressed lipid peroxidation and significantly improved oxidative status and release of NO. These results suggest that resveratrol prevents hypertrophic and apoptotic consequences induced by high blood pressure with more pronounced effects in malignant hypertension.
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Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Apoptosis , Cardiotónicos/uso terapéutico , Hipertensión Maligna/tratamiento farmacológico , Resveratrol/uso terapéutico , Animales , Antiinflamatorios/farmacología , Apoptosis/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Cardiotónicos/farmacología , Femenino , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/patología , Ventrículos Cardíacos/fisiopatología , Hemodinámica/efectos de los fármacos , Hipertensión Maligna/enzimología , Hipertensión Maligna/patología , Hipertensión Maligna/fisiopatología , Inflamación/complicaciones , Inflamación/tratamiento farmacológico , Miocardio/patología , NG-Nitroarginina Metil Éster/química , NG-Nitroarginina Metil Éster/farmacología , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Ratas Endogámicas SHR , Resveratrol/química , Resveratrol/farmacología , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Renal ischemia and reperfusion (I/R) injury is the most common cause of acute kidney injury (AKI). Pathogenesis of postischemic AKI involves hemodynamic changes, oxidative stress, inflammation process, calcium ion overloading, apoptosis and necrosis. Up to date, therapeutic approaches to treat AKI are extremely limited. Thus, the aim of this study was to evaluate the effects of hyperbaric oxygen (HBO) preconditioning on citoprotective enzyme, heme oxygenase-1 (HO-1), pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins expression, in postischemic AKI induced in normotensive Wistar and spontaneously hypertensive rats (SHR). The animals were randomly divided into six experimental groups: SHAM-operated Wistar rats (W-SHAM), Wistar rats with induced postischemic AKI (W-AKI) and Wistar group with HBO preconditioning before AKI induction (W-AKI + HBO). On the other hand, SHR rats were also divided into same three groups: SHR-SHAM, SHR-AKI and SHR-AKI + HBO. We demonstrated that HBO preconditioning upregulated HO-1 and anti-apoptotic Bcl-2 protein expression, in both Wistar and SH rats. In addition, HBO preconditioning improved glomerular filtration rate, supporting by significant increase in creatinine, urea and phosphate clearances in both rat strains. Considering our results, we can also say that even in hypertensive conditions, we can expect protective effects of HBO preconditioning in experimental model of AKI.
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Lesión Renal Aguda/prevención & control , Hemo Oxigenasa (Desciclizante)/metabolismo , Oxigenoterapia Hiperbárica/métodos , Hipertensión/complicaciones , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Daño por Reperfusión/prevención & control , Lesión Renal Aguda/etiología , Lesión Renal Aguda/patología , Lesión Renal Aguda/orina , Animales , Creatinina/metabolismo , Creatinina/orina , Modelos Animales de Enfermedad , Humanos , Hipertensión/fisiopatología , Hipertensión/terapia , Riñón/irrigación sanguínea , Riñón/patología , Riñón/fisiopatología , Masculino , Oxígeno/administración & dosificación , Fosfatos/metabolismo , Fosfatos/orina , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Eliminación Renal/fisiología , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Daño por Reperfusión/orina , Regulación hacia Arriba , Urea/metabolismo , Urea/orinaRESUMEN
Olive (Olea europaea L.) leaf extract (OLE) possesses powerful antioxidant, antihyperlipidemic, and anti-inflammatory properties. The aim was to investigated the effects of OLE on the hyperlipidemia, antioxidant defense, heme oxygenase/biliverdin reductase (HO/BVR) pathway, inflammation, and fibrosis in spontaneously hypertensive rats with focal segmental glomerulosclerosis (FSGS, a progressive form of chronic kidney disease) induced by adriamycin (2 mg/kg, i.v., twice in a 21-day period). Daily treatment of OLE (80 mg/kg, p.o.) for 6 weeks suppressed protein oxidation and lipid peroxidation (p < .01 and p < .001, respectively), significantly increased antioxidant enzymes activities and normalized antioxidant capacity, leading to the improvement of antioxidant defense independently of the HO/BVR pathway. Furthermore, the values of triglycerides (p < .01), total, and low-density lipoprotein cholesterol (p < .05, both) were improved by OLE. OLE strongly prevented glomerulosclerosis, interstitial inflammation, and fibrosis (renal injury score, FSGS: 8 ± 0.45 vs. FSGS+OLE: 4.20 ± 1.07; p < .01), as evidenced by normalized fibronectin content (p < .001), suppressed interstitial inflammatory cells infiltration and collagen deposition, without changing cytokines expressions. OLE decreased blood pressure with a tendency to reduce urine albumin loss. These data suggest that OLE may be effective in slowing down the progression of FSGS.
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Antioxidantes/uso terapéutico , Doxorrubicina/efectos adversos , Fibrosis/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Hiperlipidemias/tratamiento farmacológico , Olea/química , Estrés Oxidativo/efectos de los fármacos , Animales , Antioxidantes/farmacología , Femenino , RatasRESUMEN
Background: Acute kidney injury (AKI) as a consequence of ischemia is a common clinical event that can lead to unacceptably high morbidity and mortality. Hyperbaric oxygen (HBO2) preconditioning has been shown to prevent ischemia-reperfusion injury (IRI) in different tissues. Objectives: The aim of our study was to compare the effects of HBO2 preconditioning on renal hemodynamics, kidney function and oxidative stress in normotensive and spontaneously hypertensive rats that suffered kidney IRI. Methods: An experiment was performed on Wistar (normotensive) and spontaneously hypertensive rats (SHR). The animals were divided into the following experimental groups: sham-operated rats and rats with or without HBO2 preconditioning 24 hours before post-ischemic AKI induction. Treated rats were placed into experimental HBO2 chambers and exposed to pure oxygen twice a day for two consecutive days (2.026 bar of oxygen) for 60 minutes. AKI was performed the next morning. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 45 minutes. Results: In this study, HBO2 preconditioning significantly improved disturbed renal hemodynamics, major markers of kidney function in plasma (creatinine, urea and phosphate) as well as antioxidant enzymes (superoxide dismutase and catalase) activities in erythrocytes after AKI induction. Also, HBO2 preconditioning decreased lipid peroxidation in plasma after ischemic AKI. Positive effects were observed in both strains of rats. Conclusions: Our results suggest that HBO2 treatment improves renal hemodynamic and kidney function and decreases oxidative stress of Wistar and SHR rats with an AKI episode. Furthermore, it also implies that pre-existing hypertension does not affect the beneficial effects of HBO2 preconditioning.
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Lesión Renal Aguda/prevención & control , Oxigenoterapia Hiperbárica , Precondicionamiento Isquémico/métodos , Riñón/irrigación sanguínea , Daño por Reperfusión/prevención & control , Animales , Catalasa/sangre , Creatinina/sangre , Masculino , Estrés Oxidativo , Fosfatos/sangre , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Superóxido Dismutasa/sangre , Urea/sangreRESUMEN
Renal ischemia/reperfusion injury is a common cause of acute kidney injury (AKI) and hypertension might contribute to the increased incidence of AKI. The purpose of this study was to investigate the effects of single and combined hyperbaric oxygen (HBO) preconditioning and NADPH oxidase inhibition on oxidative stress, kidney function and structure in spontaneously hypertensive rats (SHR) after renal ischemia reperfusion injury. HBO preconditioning was performed by exposing to pure oxygen (2.026 bar) twice a day for two consecutive days for 60 minutes, and 24h before AKI induction. For AKI induction, the right kidney was removed and ischemia was performed by clamping the left renal artery for 45 minutes. NADPH oxidase inhibition was induced by apocynin (40 mg/kg b.m., intravenously) 5 minutes before reperfusion. AKI significantly increased renal vascular resistance and reduced renal blood flow, which were significantly improved after apocynin treatment. Also, HBO preconditioning, with or without apocynin treatment showed improvement on renal hemodynamics. AKI significantly increased plasma creatinine, urea, phosphate levels and lipid peroxidation in plasma. Remarkable improvement, with decrease in creatinine, urea and phosphate levels was observed in all treated groups. HBO preconditioning, solitary or with apocynin treatment decreased lipid peroxidation in plasma caused by AKI induction. Also, combined with apocynin, it increased catalase activity and solitary, glutathione reductase enzyme activity in erythrocytes. While AKI induction significantly increased plasma KIM- 1 levels, HBO preconditioning, solitary or with apocynin decreased its levels. Considering renal morphology, significant morphological alterations present after AKI induction were significantly improved in all treated groups with reduced tubular dilatation, tubular necrosis in the cortico-medullary zone and PAS positive cast formation. Our results reveal that NADPH oxidase inhibition and hyperbaric oxygen preconditioning, with or without NADPH oxidase inhibition may have beneficial effects, but their protective role should be evaluated in further studies.
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Acetofenonas/uso terapéutico , Lesión Renal Aguda/terapia , Inhibidores Enzimáticos/uso terapéutico , Oxigenoterapia Hiperbárica/métodos , NADPH Oxidasas/antagonistas & inhibidores , Daño por Reperfusión/terapia , Lesión Renal Aguda/complicaciones , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Endogámicas SHR , Daño por Reperfusión/etiología , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: Urtica dioica L. (Stinging nettle) has been used for centuries for the treatment of numerous health issues. PURPOSE: This study investigates the antioxidant capacity and the most abundant phenolic compounds of Urtica dioica L. leaf extract (UE), and its antihypertensive and antioxidative effects in vivo. STUDY DESIGN: Spontaneously hypertensive rats were supplemented with 10, 50, and 200 mg/kg/day of UE and 10 mg/kg/day of losartan during 4-week period. METHODS: In this study, HPLC analysis of UE was performed, as well as the determination of antioxidant capacity, superoxide radical scavenging activity, and metal chelating ability. Hemodynamic parameters were measured directly in anesthetized rats. Also, antioxidant enzyme activity and concentration in erythrocytes were determined, as well as systemic oxidative stress and plasma antioxidant status. RESULTS: UE showed higher ferric reducing antioxidant power and Trolox equivalent antioxidant capacity than BHT, but lower than vitamin C. Furthermore, UE showed good metal chelating ability, but weak superoxide radical scavenging activity. All three tested UE doses managed to reduce systolic and diastolic blood pressure, as well as cardiac index, and to improve the antioxidative defense by increasing the activity of superoxide dismutase and catalase, without changing the concentration of the enzymes. Moreover, UE supplementation increased plasma antioxidant capacity and reduced systemic oxidative stress. CONCLUSION: Chronic UE dietary supplementation had beneficial effects in the experimental model of essential hypertension.
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Antihipertensivos/farmacología , Antioxidantes/farmacología , Presión Sanguínea/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Urtica dioica/química , Animales , Masculino , Hojas de la Planta/química , Ratas , Ratas Endogámicas SHRRESUMEN
Haemodynamic alterations in carotid and renal arteries are associated with the severity of target organ damage in patients with hypertension. Dietary habits, such as the Mediterranean diet, regulate blood pressure and oxidative stress, thus reduce the mortality rate due to cardiovascular diseases. In this study, our aim was to evaluate the reducing activity, antioxidant capacity and metal chelating ability of standardized Olea europaea L. leaf extract (OLE), and to test its (5, 25, 50 mg/kg) acute in vivo effects, as well as oleuropein's (OP, 10 mg/kg) on oxidative stress, carotid, renal and systemic haemodynamic parameters (blood pressure, heart rate, cardiac output, peripheral resistance) in spontaneously hypertensive rats (SHR). OLE has a higher antioxidative capacity than BHT, higher reducing ability than vitamin C, and 23 times lower capacity for metal ion chelation than EDTA. All three doses of OLE, and OP, improved oxidative stress in SHR. OLE5 improved carotid and renal haemodynamics, without significant effects on systemic haemodynamics. Two different mechanisms of antihypertensive responses to OLE were observed, OLE25 was most effective in reducing cardiovascular risks by improving systemic and regional (carotid and renal) haemodynamics, peripheral and regional vascular resistance. OLE50 causes the improvement of blood pressure and cardiac performances, but tends to retain elevated vascular resistance, therefore, reducing the inflow of blood into the brain and kidneys of the SHR. The OP did not alter systemic or regional haemodynamics, suggesting others constituents responsible for changes of cardiac function, as well as carotid and renal haemodynamics in response to OLE50.
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High blood pressure is the most powerful contributor to the cardiovascular morbidity and mortality, and inverse correlation between consumption of polyphenol-rich foods or beverages and incidence of cardiovascular diseases gains more importance. Reactive oxygen species plays an important role in the development of hypertension. We found that wild thyme (a spice plant, rich in polyphenolic compounds) induced a significant decrease of blood pressure and vascular resistance in hypertensive rats. The inverse correlation between vascular resistance and plasma heme oxygenase-1 suggests that endogenous vasodilator carbon monoxide generated by heme oxidation could account for this normalization of blood pressure. Next product of heme oxidation, bilirubin (a chain-breaking antioxidant that acts as a lipid peroxyl radical scavenger), becomes significantly increased after wild thyme treatment and induces the reduction of plasma lipid peroxidation in hypertensive, but not in normotensive rats. The obtained results promote wild thyme as useful supplement for cardiovascular interventions.
Asunto(s)
Hemo-Oxigenasa 1/sangre , Hipertensión/prevención & control , Thymus (Planta)/química , Animales , Antioxidantes/química , Bilirrubina/metabolismo , Presión Sanguínea/efectos de los fármacos , Catalasa/metabolismo , Ensayo de Inmunoadsorción Enzimática , Eritrocitos/enzimología , Eritrocitos/metabolismo , Glutatión Peroxidasa/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Hemo-Oxigenasa 1/análisis , Hemodinámica/efectos de los fármacos , Hipertensión/metabolismo , Riñón/enzimología , Riñón/metabolismo , Hígado/enzimología , Hígado/metabolismo , Masculino , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Endogámicas SHR , Superóxido Dismutasa/metabolismo , Thymus (Planta)/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Oxidative stress has been widely implicated in both hypertension and chronic kidney disease (CKD). Hypertension is a major risk factor for CKD progression. In the present study we have investigated the effects of chronic single tempol (membrane-permeable radical scavenger) or losartan (angiotensin II type 1 receptor blocker) treatment, and their combination on systemic oxidative status (plasma thiobarbituric acid-reactive substances (pTBARS) production, plasma antioxidant capacity (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid, pABTS), erythrocyte antioxidant enzymes activities) and kidney oxidative stress (kTBARS, kABTS, kidney antioxidant enzymes activities), kidney function and structure in spontaneously hypertensive rats (SHR) with the early course of adriamycin-induced nephropathy. Adult SHR were divided into five groups. The control group received vehicle, while the other groups received adriamycin (2 mg/kg, i.v.) twice in a 21-day interval, followed by vehicle, losartan (L,10 mg/kg/day), tempol (T,100 mg/kg/day) or combined T+L treatment (by gavage) during a six-week period. Adriamycin significantly increased proteinuria, plasma lipid peroxidation, kidney protein oxidation, nitrite excretion, matrix metalloproteinase-1 (MMP-1) protein expression and nestin immunostaining in the kidney. Also, it decreased kidney antioxidant defense, kidney NADPH oxidase 4 (kNox4) protein expression and abolished anti-inflammatory response due to significant reduction of kidney NADPH oxidase 2 (kNox2) protein expression in SHR. All treatments reduced protein-to-creatinine ratio (marker of proteinuria), pTBARS production, kidney protein carbonylation, nitrite excretion, increased antioxidant capacity and restored kidney nestin expression similar to control. Both single treatments significantly improved systemic and kidney antioxidant defense, bioavailability of renal nitric oxide, reduced kMMP-1 protein expression and renal injury, thus retarded CKD progression. Losartan improved blood pressure, as well as tubular injury and restored anti-inflammatory defense by reverting kNox2 expression to the control level. Interestingly, tempol was more successful in reducing systemic oxidative stress, proteinuria, kMMP-1 and glomerulosclerosis. However, combined treatment failed to overcome the beneficial effects of single treatments in slowing down the progression of ADR-induced nephropathy in SHR.
Asunto(s)
Antihipertensivos/uso terapéutico , Antioxidantes/uso terapéutico , Óxidos N-Cíclicos/uso terapéutico , Losartán/uso terapéutico , Estrés Oxidativo , Proteinuria/tratamiento farmacológico , Insuficiencia Renal Crónica/tratamiento farmacológico , Animales , Antihipertensivos/administración & dosificación , Antihipertensivos/farmacología , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Óxidos N-Cíclicos/administración & dosificación , Óxidos N-Cíclicos/farmacología , Quimioterapia Combinada , Femenino , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Losartán/administración & dosificación , Losartán/farmacología , Metaloproteinasa 1 de la Matriz/genética , Metaloproteinasa 1 de la Matriz/metabolismo , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , NADPH Oxidasa 2 , NADPH Oxidasa 4 , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Nestina/genética , Nestina/metabolismo , Proteinuria/metabolismo , Proteinuria/patología , Ratas , Ratas Endogámicas SHR , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Marcadores de SpinRESUMEN
Many studies demonstrated that angiotensin 2 type 1 receptor (AT1R) blockade accelerates renal recovery in post-ischaemic kidney but there are many controversies related to its net effect on kidney structure and function. During the past years, our research group was trying to define the pathophysiological significance of the renin-angiotensin system on post-ischemic acute renal failure (ARF) development in normotensive Wistar as well as hypertensive rats (SHR). This review mostly summarizes our experience in that field. Our previous studies in normotensive rats revealed that AT1R blockade, except slightly renal vascular resistance improvement, had no other obvious beneficial effects, and therefore implies angiotensin 2 (Ang-2) overexpression as non-dominant on kidney reperfusion injuries development. Similarly it was observed in Wistar rats with induced mild (L-NAME, 3 mg/kg b.w.) nitric oxide (NO) deficiency. Expectably, in strong induced (L-NAME, 10 mg/kg b.w.) NO deficiency associated with ARF, massive tubular injuries indicate harmful effects of AT1R blockade, implying strongly disturbed glomerular filtration and suggesting special precaution related to AT1R blockers usage. Opposite to previous, by our opinion, AT1R antagonism promises new advance in treatment of essentially hypertensive subjects who develop ARF. Increased glomerular filtration, diminished oxidative stress, and most importantly improved tubular structure in postishemic SHR treated with AT1R blocker losartan, implicate Ang-2 over production as potently agent in the kidney ischemic injury, partly trough generation of reactive oxygen species. These data contribute understanding the pathogenesis of this devastating illness in hypertensive surroundings.
Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Hipertensión/tratamiento farmacológico , Riñón/efectos de los fármacos , Losartán/farmacología , Daño por Reperfusión/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/fisiopatología , Animales , Regulación de la Expresión Génica , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/fisiopatología , Riñón/irrigación sanguínea , Riñón/metabolismo , Riñón/fisiopatología , Óxido Nítrico/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Arteria Renal/efectos de los fármacos , Arteria Renal/metabolismo , Arteria Renal/fisiopatología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/genética , Daño por Reperfusión/metabolismo , Daño por Reperfusión/fisiopatología , Resistencia Vascular/efectos de los fármacosRESUMEN
Limited numbers of studies include research of microvibration therapy in experimental models. We examined effects of chronic vibroacustic-microvibration treatment on haemodynamics and anti-oxidative defense in experimental hypertension. Study was performed on chronically treated hypertensive and normotensive Wistar rats. Mean arterial pressure (MAP), cardiac output (CO), renal blood flow (RBF), glomerular filtration and activity of anti-oxidative enzymes were determined after three weeks treatment. Vibroacustic treatment had no influence on MAP and CO, but RBF was increased in both groups of treated rats. Additionally, vibroacustic treatment enhanced diuresis and increased glomerular filtration in hypertensive rats. Glutathione peroxidase (GSH-Px) activity was elevated in both treated rat strains, but activity of superoxide dismutase was unchanged. We conclude that microvibration treatment doesn't ameliorate hypertension but improves renal blood supply (trough diminished renal vascular resistance), glomerular filtration, diuresis, and enhances glutathione dependent anti-oxidant defense with more important beneficials in hypertensive animals.