RESUMO
Acute kidney injury (AKI) has been increasingly reported in critically-ill COVID-19 patients. Moreover, there was significant positive correlation between COVID-19 deaths and renal disorders in hospitalized COVID-19 patients with underlying comorbidities who required renal replacement therapy. It has suggested that death in COVID-19 patients with AKI is 3-fold higher than in COVID-19 patients without AKI. The pathophysiology of COVID-19-associated AKI could be attributed to unspecific mechanisms, as well as COVID-19-specific mechanisms such as direct cellular injury, an imbalanced renin-angiotensin-aldosterone system, pro-inflammatory cytokines elicited by the viral infection and thrombotic events. To date, there is no specific treatment for COVID-19 and its associated AKI. Luteolin is a natural compound with multiple pharmacological activities, including anticoronavirus, as well as renoprotective activities against kidney injury induced by sepsis, renal ischemia and diverse nephrotoxic agents. Therefore, in this review, we mechanistically discuss the anti-SARS-CoV-2 and renoprotective activities of luteolin, which highlight its therapeutic potential in COVID-19-AKI patients.
Assuntos
Injúria Renal Aguda , Tratamento Farmacológico da COVID-19 , COVID-19 , Humanos , COVID-19/complicações , Luteolina/farmacologia , Luteolina/uso terapêutico , SARS-CoV-2 , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/etiologia , Estado TerminalRESUMO
BACKGROUND: Acute Kidney Injury (AKI), a common disease of the urinary system, can be induced by high doses of gentamicin (GM). The renin-angiotensin system exerts a key role in the progression of the AKI since elevated intrarenal levels of Ang II, and ACE activity is found in this condition. However, it is unknown whether oral administration of angiotensin (Ang)-(1-7), a heptapeptide that evokes opposite effects of Ang II, may attenuate the renal injuries induced by gentamicin. OBJECTIVES: To evaluate the effects of Ang-(1-7) on GM-induced renal dysfunction in rats. METHODS: AKI was induced by subcutaneous administration of GM (80 mg/Kg) for 5 days. Simultaneously, Ang-(1-7) included in hydroxypropyl ß-cyclodextrin (HPßCD) was administered by gavage [46 µg/kg HPßCD + 30 µg/kg Ang-(1-7)]. At the end of the treatment period (sixth day), the rats were housed in metabolic cages for renal function evaluation. Thereafter, blood and kidney samples were collected. RESULTS: Ang-(1-7) attenuated the increase of the plasmatic creatinine and proteinuria caused by GM but did not change the glomerular filtration rate nor tubular necrosis. Ang-(1-7) attenuated the increased urinary flow and the fractional excretion of H2O and potassium observed in GM rats but intensified the elevated excretion of sodium in these animals. Morphological analysis showed that Ang-(1-7) also reduced the tubular vacuolization in kidneys from GM rats. CONCLUSION: Ang-(1-7) promotes selective beneficial effects in renal injuries induced by GM.
Assuntos
Injúria Renal Aguda , Angiotensina I/farmacologia , Gentamicinas/efeitos adversos , Fragmentos de Peptídeos/farmacologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Administração Oral , Animais , Avaliação de Medicamentos , Gentamicinas/farmacologia , Masculino , Ratos , Ratos WistarRESUMO
Data obtained from several intensive care units around the world have provided substantial evidence of the strong association between impairment of the renal function and in-hospital deaths of critically ill COVID-19 patients, especially those with comorbidities and requiring renal replacement therapy (RRT). Acute kidney injury (AKI) is a common renal disorder of various etiologies characterized by a sudden and sustained decrease of renal function. Studies have shown that 5-46% of COVID-19 patients develop AKI during hospital stay, and the mortality of those patients may reach up to 100% depending on various factors, such as organ failures and RRT requirement. Catechins are natural products that have multiple pharmacological activities, including anti-coronavirus and reno-protective activities against kidney injury induced by nephrotoxic agents, obstructive nephropathies and AKI accompanying metabolic and cardiovascular disorders. Therefore, in this review, we discuss the anti-SARS-CoV-2 and reno-protective effects of catechins from a mechanistic perspective. We believe that catechins may serve as promising therapeutics in COVID-19-associated AKI due to their well-recognized anti-SARS-CoV-2, and antioxidant and anti-inflammatory properties that mediate their reno-protective activities.
Assuntos
Injúria Renal Aguda/etiologia , Antivirais/farmacologia , COVID-19/complicações , Catequina/farmacologia , Substâncias Protetoras/farmacologia , Injúria Renal Aguda/tratamento farmacológico , Animais , Antivirais/química , Antivirais/uso terapêutico , Catequina/química , Catequina/uso terapêutico , Humanos , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: The blockade of the progression or onset of pathological events is essential for the homeostasis of an organism. Some common pathological mechanisms involving a wide range of diseases are the uncontrolled inflammatory reactions that promote fibrosis, oxidative reactions, and other alterations. Natural plant compounds (NPCs) are bioactive elements obtained from natural sources that can regulate physiological processes. Inflammation is recognized as an important factor in the development and evolution of chronic renal damage. Consequently, any compound able to modulate inflammation or inflammation-related processes can be thought of as a renal protective agent and/or a potential treatment tool for controlling renal damage. The objective of this research was to review the beneficial effects of bioactive natural compounds on kidney damage to reveal their efficacy as demonstrated in clinical studies. METHODS: This systematic review is based on relevant studies focused on the impact of NPCs with therapeutic potential for kidney disease treatment in humans. RESULTS: Clinical studies have evaluated NPCs as a different way to treat or prevent renal damage and appear to show some benefits in improving OS, inflammation, and antioxidant capacity, therefore making them promising therapeutic tools to reduce or prevent the onset and progression of KD pathogenesis. CONCLUSIONS: This review shows the promising clinical properties of NPC in KD therapy. However, more robust clinical trials are needed to establish their safety and therapeutic effects in the area of renal damage.
Assuntos
Nefropatias/tratamento farmacológico , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Antioxidantes/farmacologia , Berberina/farmacologia , Beta vulgaris , Betalaínas/farmacologia , Produtos Biológicos/farmacologia , Catequina/farmacologia , Curcumina/farmacologia , Dissulfetos/farmacologia , Flavonoides/farmacologia , Humanos , Isotiocianatos/farmacologia , Rim/efeitos dos fármacos , Rim/patologia , Punica granatum , Resveratrol/farmacologia , Ácidos Sulfínicos/farmacologia , Sulfóxidos/farmacologia , Xantofilas/farmacologiaRESUMO
Rudgea viburnoides is widely found in the Brazilian Cerrado, and commonly used in Brazilian folk medicine. In this study, we evaluated the effects of prolonged administration of the aqueous extract from R. viburnoides leaves (AERV) on impaired redox status, renal dysfunction, and cardiovascular damage in 2K1C hypertensive rats, as well as its chemical composition by LC-DAD-MS. Renal hypertension (two kidney, one-clip model) was surgically induced in male Wistar rats and AERV (30, 100 and 300 mg/kg) was administered orally five weeks after surgery for 28 days. Renal function was assessed and urinary electrolytes, pH, and density were measured. Electrocardiography, blood pressure and heart rate were recorded. Cardiac and mesenteric vascular beds were isolated for cardiac morphometry and evaluation of vascular reactivity, and aortic rings were also isolated for measurement of cyclic guanosine monophosphate levels, and the redox status was assessed. Prolonged treatment with AERV preserved urine excretion and electrolyte levels (Na+, K+, Ca2+ and Cl-), reversed electrocardiographic changes, left ventricular hypertrophy and changes in vascular reactivity induced by hypertension, and reduced blood pressure and heart rate. This effect was associated with a positive modulation of tissue redox state, activation of the NO/cGMP pathway, and inhibition of the angiotensin-converting enzyme. Glycosylated iridoids, chlorogenic acids, glycosylated triterpenes, O-glycosylated flavonols, and triterpenoid saponins were annotated. AERV showed no acute toxicity in female Wistar rats. Therefore, AERV treatment reduced the progression of cardiorenal disease in 2K1C hypertensive rats, which can be involved with an important attenuation of oxidative stress, angiotensin-converting enzyme inhibition, and activation of the NO/cGMP pathway.
RESUMO
The inflammatory mediator and oxidant agent storm caused by the SARS-CoV-2 infection has been strongly associated with the failure of vital organs observed in critically ill patients with coronavirus disease 2019 (COVID-19) and the death of thousands of infected people around the world. Acute kidney injury (AKI) is a common renal disorder characterized by a sudden and sustained decrease in renal function with a critical influence on poor prognosis and lethal clinical outcomes of various etiologies, including some viral infection diseases. It is known that oxidative stress and inflammation play key roles in the pathogenesis and development of AKI. Quercetin is a natural substance that has multiple pharmacological properties, such as anti-inflammatory action, and is used as a dietary supplement. There is evidence of the anti-coronavirus activities of this compound, including against the target SARS-CoV-2 3CLpro. The ability to inhibit coronavirus and its inflammatory processes is strongly desired in a new drug for the treatment of COVID-19. Therefore, in this review, the dual effect of quercetin is discussed from a mechanistic perspective in relation to AKI kidney injury and its nephroprotective potential to SARS-CoV-2 patients.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , COVID-19/complicações , Quercetina/farmacologia , Injúria Renal Aguda/etiologia , Animais , COVID-19/epidemiologia , Humanos , Morbidade , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Quercetina/uso terapêutico , Tratamento Farmacológico da COVID-19RESUMO
Previous studies have shown that accumulation of advanced glycation end products (AGEs) can be the cause of diabetic nephropathy (DN) in diabetic patients. Dihydrochalcone 3'-O-ß-d-glucopyranosyl α,4,2',4',6'-pentahydroxyâ»dihydrochalcone (1) is a powerful antiglycation compound previously isolated from Eysenhardtia polystachya. The aim was to investigate whether (1) was able to protect against diabetic nephropathy in streptozotocin (STZ)-induced diabetic mice, which displayed renal dysfunction markers such as body weight, creatinine, uric acid, serum urea, total urinary protein, and urea nitrogen in the blood (BUN). In addition, pathological changes were evaluated including glycated hemoglobin (HbA1c), advanced glycation end products (AGEs) in the kidney, as well as in circulation level and pro-inflammatory markers ICAM-1 levels in diabetic mice. After 5 weeks, these elevated markers of dihydrochalcone treatment (25, 50 and 100 mg/kg) were significantly (p < 0.05) attenuated. In addition, they ameliorate the indices of renal inflammation as indicated by ICAM-1 markers. The kidney and circulatory AGEs levels in diabetic mice were significantly (p < 0.05) attenuated by (1) treatment. Histological analysis of kidney tissues showed an important recovery in its structure compared with the diabetic group. It was found that the compound (1) attenuated the renal damage in diabetic mice by inhibiting AGEs formation.
Assuntos
Chalconas/uso terapêutico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/tratamento farmacológico , Fabaceae/química , Produtos Finais de Glicação Avançada/sangue , Casca de Planta/química , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Chalconas/síntese química , Chalconas/química , Chalconas/farmacologia , Creatinina/sangue , Nefropatias Diabéticas/patologia , Ingestão de Líquidos , Comportamento Alimentar , Glucose/metabolismo , Hemoglobinas Glicadas/metabolismo , Mediadores da Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos Endogâmicos C57BL , Niacinamida , Tamanho do Órgão/efeitos dos fármacos , Ratos , Estreptozocina , Ureia/sangue , Ácido Úrico/sangue , UrinaRESUMO
OBJECTIVE: The objective of this study is to evaluate the efficacy of a tightly controlled renoprotective protocol in systemic lupus erythematosus (SLE) patients with persistent proteinuria. METHODS: Thirteen SLE patients with nephritis and persistent proteinuria (>1 g/24 hours) were included. The protocol consisted of regular clinical evaluations every two weeks to assess blood pressure (BP, target <130/80 mmHg), adherence to therapy, diet and smoking. No change in immunosuppressive drugs was allowed but reduction of glucocorticoid dose was permitted if indicated. Clinical, laboratory and treatment evaluations were performed at baseline and at the end of the study (after three months). RESULTS: SLE patients had a mean age of 37.85 ± 7.68 years and disease duration of 9.85 ± 7.29 years. At baseline, patients had a mean duration of maintenance therapy of 10.38 ± 7.56 months, 12 with mycophenolate mofetil (92.3%) and one with azathioprine (7.7%). At least one dose optimization of antihypertensive regimen was required in all patients during the study. Seven patients (53.8%) had BP>130/80mmHg at baseline. At the end, 11 patients (84.6%) achieved stable BP target; 92.3% were using an angiotensin-converting enzyme inhibitor, 53.9% an angiotensin receptor blocker, and 46.2% were using combined therapy. All patients had a significant reduction in proteinuria levels (2.26 ± 1.09 vs 0.88 ± 0.54 g/24 hours, p < 0.001) and 61.5% achieved proteinuria <1 g/24 hours. A significant decrease in mean prednisone dose was observed (10.96 ± 6.73 vs 5.38 ± 3.36 mg/day, p = 0.013) as well as mean Systemic Lupus Erythematosus Disease Activity Index score (4.38 ± 0.72 vs 3.08 ± 1.86, p = 0.043). No significant changes were identified in serum creatinine, albumin, potassium, complement 3 and complement 4 levels ( p > 0.05). CONCLUSION: This study provides evidence that a tightly controlled renoprotective protocol is effective in reducing persistent proteinuria in lupus nephritis. The concomitant reduction of prednisone without any change in immunosuppression reinforces the importance of strategies beyond the treatment of nephritis activity.
Assuntos
Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Prednisona/administração & dosagem , Proteinúria/tratamento farmacológico , Adulto , Azatioprina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Brasil , Quimioterapia Combinada , Feminino , Humanos , Nefrite Lúpica/complicações , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: One of the medicinal plants widely used by the population in the treatment of hypertension, atherosclerosis and circulatory disorders is Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae), popularly known as 'sete sangrias', being found in Brazil, Hawaii and in South Pacific Islands. Despite the widespread use of this species by the population, its long-term antihypertensive and cardioprotective activities have not yet been scientifically evaluated. PURPOSE: To evaluate the possible cardioprotective effects of an ethanol-soluble fraction obtained from C. carthagenensis (ESCC) using ovariectomized hypertensive rats to simulate a broad part of the female population over 50 years of age affected by hypertension. In addition, the molecular mechanism that may be responsible for its cardiorenal protective effects was also explored. METHODS: Female Wistar rats were submitted to surgical procedures of bilateral ovariectomy and induction of renovascular hypertension (two-kidneys, one-clip model). The sham-operated group was used as negative control. ESCC was obtained and a detailed phytochemical investigation about its main secondary metabolites was performed. ESCC was orally administered at doses of 30, 100 and 300 â¯mg/kg, daily, for 28 days, 5 weeks after surgery. Enalapril (15⯠mg/kg) was used as standard antihypertensive drug. Renal function was evaluated on days 1, 7, 14, 21 and 28. At the end of the experimental period, systolic, diastolic, mean arterial pressure and heart rate were recorded. The activity of the tissue enzymatic antioxidant system, thiobarbituric acid reactive substances, nitrotyrosine, nitrite, aldosterone and vasopressin levels, in addition to the activity of the angiotensin-converting enzyme were also evaluated. Additionally, vascular reactivity to acetylcholine, sodium nitroprusside, and phenylephrine, and the role of nitric oxide, prostaglandins, and K+ channels in the vasodilator response of ESCC on the mesenteric vascular bed were also investigated. RESULTS: ESCC-treatment induced an important cardiorenal protective response, preserving renal function and preventing elevation of blood pressure and heart rate in ovariectomized hypertensive rats. In addition, prolonged treatment with ESCC recovered mesenteric vascular reactivity at all doses used. This effect was associated with an important modulation of the antioxidant defense system with a possible increase in NO bioavailability. Additionally, NO/cGMP activation and K+ channel opening-dependent vasodilator effect was observed on the mesenteric vascular bed, indicating a potential mechanism for the cardiovascular effects of ESCC. CONCLUSION: A 28-days ESCC treatment reduces the progression of the cardiorenal disease in ovariectomized hypertensive rats. These effects seem to be involved with an attenuation of oxidative and nitrosative stress, affecting endothelial nitric oxide production and K+ channel opening in smooth muscle cells.
Assuntos
Anti-Hipertensivos/farmacologia , Cuphea/química , Hipertensão Renovascular/tratamento farmacológico , Extratos Vegetais/farmacologia , Aldosterona/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , GMP Cíclico/metabolismo , Endotélio Vascular/efeitos dos fármacos , Feminino , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Estresse Nitrosativo , Oxirredução , Estresse Oxidativo , Peptidil Dipeptidase A/metabolismo , Compostos Fitoquímicos/farmacologia , Plantas Medicinais/química , Canais de Potássio/metabolismo , Ratos , Ratos Wistar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Vasodilatadores/farmacologia , Vasopressinas/metabolismoRESUMO
A lesão renal aguda (LRA) é uma complicação comum no paciente grave e está associada à alta mortalidade, tendo a sepse como o mais prevalente fator de risco em pacientes críticos. A LRA na sepse está envolvida com estresse oxidativo e vasoconstrição. Diversas medidas terapêuticas para minimizar os danos renais na sepse já foram investigadas, com destaque para os fármacos antioxodantes, e não se confirmaram como intervenção a ser incorporada na clínica. O objetivo desse estudo foi avaliar a resposta inflamatória sistêmica na sepse, a função renal e os efeitos renoprotetores do vasodilatador cilostazol e dos antioxidantes n-acetilcisteína (NAC) e diosmina hesperidina no modelo de sepse experimental. Foram avaliados parâmetros sistêmicos, o perfil inflamatório renal, intestinal e pulmonar (TGF- e interleucina 6-IL-6), a função renal (FR-clearance de creatinina), a geração urinária de peróxidos (PU) e a análise histopatológica dos rins. Foram utilizados ratos Wistar, machos, divididos em 5 grupos: Sham (controle); Sepse: sepse induzida pela técnica de ligadura e punção do cecon (LPC); Sepse+Cilostazol; Sepse+N-acetilcisteína (NAC) e Sepse+Diosmina. Os resultados mostraram que o grupo Sepse apresentou elevação de TGF- e IL-6 e parâmetros globais como redução da temperatura e hipotensão que caracterizaram o padrão da sepse. Os grupos sepse, tratados ou não, mostraram redução da função renal, com diminuição do fluxo urinário e elevação do parâmetro oxidante analisado, os PUs. Apenas o grupo Sepse+Diosmina demonstrou atenuar a redução da FR desencadeada pela sepse e redução dos PUs na comparação ao grupo Sepse. Todos os grupos sepse apresentaram alterações histológicas renais. O estudo confirmou a LRA por sepse, sendo que apenas o fármaco diosmina hesperidina contribuiu para a melhora da função renal e redução do estresse oxidativo.
Acute renal injury (AKI) is a common complication in critically ill patient and it is associated with high mortality, with sepsis being the most prevalent risk factor for renal failure in critically ill patients. LRA in sepsis is involved with oxidative stress and vasoconstriction. Therapeutic initiatives aimed at minimizing renal damage in sepsis were not confirmed. This study evaluated the systemic inflammatory response in sepsis, renal function and renoprotective effects of the vasodilator cilostazol and the antioxidants n-acetylcysteine (NAC) and diospenes hesperidin. Systemic parameters, the inflammatory renal, in the intestine and in the lungs profile (TGF- and interleukin 6-IL-6), renal function (RF-creatinine clearance), urinary peroxides generation (PU) and histopathological analysis of the kidneys were performed. Male Wistar rats were divided into 5 groups: Sham (control); Sepsis: sepsis induced by the technique of ligation and puncture of the cecon (LPC); Sepsis+cilostazol; Sepsis+N-acetylcysteine (NAC) and Sepsis+diosmin. The results showed that the Sepsis group presented elevation of TGF- and IL-6 and global parameters such as temperature reduction and hypotension characterizing the sepsis pattern. Sepsis groups showed reduced renal function and urinary flow and elevation on UPs. The Sepsis+Diosmina group was the only one to attenuate RF reduction and PU reduction when compared to the Sepsis group. All sepsis groups had renal histological changes. The study confirmed that sepsis induces AKI, being diosmin hesperidin the only agent to contribute to the improvement of renal function and reduction of oxidative stress.
Assuntos
Enfermagem , Sepse , Ratos , Injúria Renal Aguda , AntioxidantesRESUMO
Introducción: La Enfermedad Renal es un problema de salud mundial. El Factor de Crecimiento Epidérmico actúa como citoprotector y trófico reparador. Objetivo: Evaluar el efecto reno-protector y reno-reparador del Factor de Crecimiento Epidérmico en biomodelo de Insuficiencia Renal Crónica. Material y Métodos: Se estudiaron 120 ratas, Wistar, en 6 grupos: Control Negativo y positivo, Solución Salina Dosis Única y Múltiple, Factor de Crecimiento Epidérmico Dosis Única y Múltiple. Se aplicó para efecto reno-protector dosis única antes del daño, y para el reno-reparador dosis múltiples posterior al daño, a razón de 100 µg/kg de peso. Resultados: La creatinina, urea y ácido úrico disminuyeron significativamente en los grupos experimentales, con mayor disminución para el grupo experimental dosis única, por lo que el efecto reno-protector fue mayor que el reno-reparador para los esquemas de tratamiento utilizados. Conclusiones: El Factor de Crecimiento Epidérmico mostró efecto reno-protector y reno-reparador al disminuir las variables hematológicas de daño renal(AU)
Introduction: Kidney disease is a world health problem. Epidermic Growth Factor acts as cyto-protector, and trophic restorative. Objective: To assess the reno-protective and reno-restorative effect of the Epidermal Growth Factor in biomodel of Chronic Renal Failure. Material and Methods: 120 Wistar rats were studied in 6 groups: Negative and Positive Control, Saline Solution Single-Dose and Multiple-Dose, Epidermal Growth Factor Single-Dose and Multiple-Dose. A single dose was applied before the damage for the reno-protective effect, and multiple doses after the damage for the reno-restorative effect, at a rate of 100 µg/kg of weight. Results: Creatinine, urea, and uric acid diminished significantly in the experimental groups, with a higher decrease for experimental group with single dose; therefore, the reno-protective effect was higher than reno-restorative one for the treatment patterns used. Conclusions: Epidermal Growth Factor showed reno-protective and reno-restorative effect by diminishing the hematological variables in kidney damage(AU)