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1.
Medicine (Baltimore) ; 98(49): e18167, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31804331

RESUMO

RATIONALE: Renal actinomycosis is a rare clinical infection, subacute to chronic presentation caused by the Actinomyces bacteria. Actinomyces israelii is diagnosed in the overpowering majority of reported cases. Abdominopelvic manifestation forms 10% to 20% of all actinomycosis, and may be misdiagnosed as either a malignancy or chronic inflammation due to the lower correct preoperative diagnostic rate (<10%). PATIENT CONCERNS: A 38-year-old man with alcoholic liver cirrhosis experienced right flank pain, abdominal pain, and fever for 3 days. Leukocytosis, acute kidney injury, and impaired liver function were found. A computed tomographic scan demonstrated multiple renal cystic lesions, along with fluid accumulation at the right subphrenic and retroperitoneal spaces. DIAGNOSES: Renal actinomycosis was confirmed via cultures of both the abscess and nephrectomy specimen which grew A israelii and the pathological findings of multiple renal abscesses of actinomycosis with the characteristics of sulfur granules. INTERVENTIONS: A nephrectomy was performed for an inadequate percutaneous drainage of renal abscess. OUTCOMES: A full course of antibiotics with intravenous penicillin G (3 million units every 4 hours) was prescribed for 2 weeks, followed by oral penicillin V given at a dose of 2 grams per day for 6 months at our out-patient facility. LESSONS: A precise diagnosis of primary renal actinomycosis depends on any histopathological findings and/or cultures of specimens. A high dose of intravenous penicillin G is the first choice, followed by oral penicillin V, with the duration of each being dependent upon the individual condition.


Assuntos
Abscesso Abdominal/complicações , Actinomicose/complicações , Nefropatias/complicações , Cirrose Hepática Alcoólica/complicações , Espaço Retroperitoneal/patologia , Abscesso Abdominal/tratamento farmacológico , Actinomicose/tratamento farmacológico , Actinomicose/cirurgia , Adulto , Antibacterianos/uso terapêutico , Humanos , Nefropatias/tratamento farmacológico , Nefropatias/cirurgia , Masculino , Nefrectomia
2.
Adv Exp Med Biol ; 1182: 243-262, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31777022

RESUMO

The mechanisms of kidney diseases, such as acute kidney injury (AKI) and chronic kidney disease (CKD), have been intensively studied. Nonetheless, the morbidity and mortality of AKI and CKD increased in recent years. Recently, natural products have been increasingly recognized as an alternative source for treating renal diseases on account of the conventional experience and the multi-target characteristics. Ganoderma lucidum (G. lucidum, Lingzhi) has been used for centuries as nutraceuticals and alternative medicine to improve health and to treat numerous diseases. Benefiting from various biological activities, such as anti-oxidation, anti-inflammation, anti-tumor growth and metastasis, etc., G. lucidum has been proved to exhibit significant role in preventing and treating various kidney diseases. In this chapter, we review certain researches and provide comprehensive insights into the renoprotective effects of G. lucidum.


Assuntos
Produtos Biológicos/farmacologia , Nefropatias/tratamento farmacológico , Reishi/química , Humanos
3.
Life Sci ; 239: 117015, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31678551

RESUMO

Obstructive renal injury and drug-induced nephrotoxicity are the two most common causes of renal fibrosis diseases. However, whether these two different pathogeny induced same pathological outcomes contain common genetic targets or signaling pathway, the current research has not paid great attention. GSE121190 and GSE35257 were downloaded from the Gene Expression Omnibus (GEO) database. While GSE121190 represents a differential expression profile in kidney of mice with unilateral ureteral obstruction (UUO) model, GSE35257 represents cisplatin nephrotoxicity model. By using GEO2R, 965 differential expression genes (DEGs) in GSE121190 and 930 DEGs in GSE35257 were identified. 43 co-DEGs were shared and were extracted for protein-protein interaction (PPI) analysis. Subsequently, three shared pathways including glycolysis/gluconeogenesis, fatty acid degradation and pathways in cancer were involved in two models with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We reconfirmed that these three pathways have relatively high scores by using Gene Set Enrichment Analysis (GSEA) software. Additionally, further bioinformatic analysis showed that Aldehyde dehydrogenase-2 (Aldh2) involved in the progression of renal fibrosis by mediating glycolysis pathway. Then real-time PCR and western blotting were performed to validate the expression of Aldh2 in kidney tissue after three different etiologies that caused renal fibrosis. Basically consistent with our bioinformatics results, our experiment showed that the expression of Aldh2 is the most significantly decreased in the UUO model, followed by ischemia-reperfusion injury (IRI) model and finally the cisplatin-induced model. Thus, Aldh2 can act as a common potential genetic target for different renal fibrosis diseases.


Assuntos
Aldeído-Desidrogenase Mitocondrial/genética , Nefropatias/tratamento farmacológico , Nefropatias/enzimologia , Aldeído-Desidrogenase Mitocondrial/efeitos dos fármacos , Animais , Cisplatino/toxicidade , Biologia Computacional , Bases de Dados Genéticas , Fibrose , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/genética , Nefropatias/induzido quimicamente , Nefropatias/genética , Camundongos , Camundongos Endogâmicos BALB C , Mapas de Interação de Proteínas , Obstrução Ureteral/complicações , Obstrução Ureteral/genética , Obstrução Ureteral/patologia
4.
Adv Clin Exp Med ; 28(10): 1393-1401, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31518496

RESUMO

BACKGROUND: Cyclosporine-A (CsA) is widely used for immunosuppressive therapy in renal transplantation. Nephrotoxicity is the main dose-limiting undesirable consequence of CsA. Urotensin II (U-II), a novel peptide with a powerful influence on vascular biology, has been added to the list of potential renal vascular regulators. Upregulation of the urotensin receptors and elevation of plasma U-II levels are thought to possibly play a role in the etiology of renal failure. OBJECTIVES: The present study examines this hypothesis by evaluating renal function and histology with regard to the potential role of U-II and its antagonist, palosuran, in the pathogenesis of CsA-induced nephrotoxicity in rats. MATERIAL AND METHODS: Male Sprague-Dawley rats were treated with CsA (15 mg/kg, for 21 days, intraperitoneally) or CsA + palosuran (300 mg/kg, for 21 days). Renal function was measured and histopathology, U-II immunostaining and protein detection with western blotting of the kidneys were performed. RESULTS: Cyclosporine-A administration caused a marked decline in creatinine clearance (Ccr). Fractional sodium excretion (FENa) tended to increase in the CsA-treated rats. Plasma U-II levels decreased in the CsA-treated rats. Cyclosporine-A treatment resulted in a marked deterioration in renal histology and an increase in the expression of U-II protein in the kidneys. Palosuran's improvement of renal function manifested as a significant decrease in serum creatinine levels and a significant increase in urine creatinine levels, resulting in a marked increase in Ccr. Palosuran produced a significant normalization of kidney histology and prevented an increase in U-II expression. CONCLUSIONS: Cyclosporine-A-induced renal impairment was accompanied by an increase in U-II expression in kidneys and a contrary decrease in systemic U-II levels. Palosuran improved the condition of rats suffering from renal dysfunction by preventing the decrease in renal U-II expression without affecting the systemic levels of U-II. The protective effect of palosuran in CsA nephrotoxicity is possibly independent of its U-II receptor antagonism.


Assuntos
Ciclosporina/toxicidade , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Urotensinas/antagonistas & inibidores , Animais , Creatinina/sangue , Creatinina/urina , Ciclosporina/efeitos adversos , Imunossupressores , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Masculino , Modelos Animais , Quinolinas , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Ureia/análogos & derivados
5.
Int J Mol Sci ; 20(18)2019 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-31500276

RESUMO

In various models of chronic kidney disease, the amount and localization of Cx43 in the nephron is known to increase, but the intracellular pathways that regulate these changes have not been identified. Therefore, we proposed that: "In the model of renal damage induced by infusion of angiotensin II (AngII), a RhoA/ROCK-dependent pathway, is activated and regulates the abundance of renal Cx43". In rats, we evaluated: 1) the time-point where the renal damage induced by AngII is no longer reversible; and 2) the involvement of a RhoA/ROCK-dependent pathway and its relationship with the amount of Cx43 in this irreversible stage. Systolic blood pressure (SBP) and renal function (urinary protein/urinary creatinine: Uprot/UCrea) were evaluated as systemic and organ outcomes, respectively. In kidney tissue, we also evaluated: 1) oxidative stress (amount of thiobarbituric acid reactive species), 2) inflammation (immunoperoxidase detection of the inflammatory markers ED-1 and IL-1ß), 3) fibrosis (immune detection of type III collagen; Col III) and 4) activity of RhoA/ROCK (amount of phosphorylated MYPT1; p-MYPT1). The ratio Uprot/UCrea, SBP, oxidative stress, inflammation, amount of Cx43 and p-MYPT1 remained high 2 weeks after suspending AngII treatment in rats treated for 4 weeks with AngII. These responses were not observed in rats treated with AngII for less than 4 weeks, in which all measurements returned spontaneously close to the control values after suspending AngII treatment. Rats treated with AngII for 6 weeks and co-treated for the last 4 weeks with Fasudil, an inhibitor of ROCK, showed high SBP but did not present renal damage or increased amount of renal Cx43. Therefore, renal damage induced by AngII correlates with the activation of RhoA/ROCK and the increase in Cx43 amounts and can be prevented by inhibitors of this pathway.


Assuntos
Angiotensina II/efeitos adversos , Conexina 43/metabolismo , Nefropatias/metabolismo , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Animais , Creatinina/urina , Modelos Animais de Doenças , Regulação da Expressão Gênica , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Nefropatias/urina , Masculino , Estresse Oxidativo , Ratos , Transdução de Sinais , Fatores de Tempo
6.
Methodist Debakey Cardiovasc J ; 15(2): 158-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31384382

RESUMO

This column is supplied by Benjamin J. Lee, MD, MAS, an assistant professor of clinical medicine at both the Houston Methodist Institute for Academic Medicine and Weill Cornell Medical College. After earning his medical degree at Harvard Medical School, Dr. Lee completed a residency in internal medicine at the University of California, San Francisco (UCSF). He subsequently completed a nephrology fellowship at UCSF while simultaneously obtaining a Master of Advanced Study in clinical research from the UCSF Department of Epidemiology and Biostatistics. Dr. Lee is a Fellow of the American Society of Nephrology, a Certified Hypertension Specialist through the American Hypertension Specialist Certification Program, and a member of the American Society of Transplantation. He maintains his clinical practice with the Houston Kidney Consultants.


Assuntos
Cianose/etiologia , Cardiopatias Congênitas/complicações , Nefropatias/etiologia , Rim/fisiopatologia , Cianose/diagnóstico , Cianose/fisiopatologia , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/tratamento farmacológico , Cardiopatias Congênitas/fisiopatologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/fisiopatologia , Prognóstico , Fatores de Risco
7.
Curr Top Med Chem ; 19(20): 1818-1849, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456521

RESUMO

Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/farmacologia , Nefropatias/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Nefropatias/metabolismo
8.
Adv Exp Med Biol ; 1155: 369-380, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468415

RESUMO

The present study was carried out in diabetic rats to examine the effects of ethanol (EtOH) and taurine (TAU), singly and in combination, in reducing the changes of laboratory test values indicating renal dysfunction. For this purpose, male Sprague-Dawley rats, 250-280 g in weight and in groups of 6, were made diabetic with a single, 60 mg/kg intraperitoneal dose of streptozotocin in 10 mM citrate buffer pH 4.5. On day 15 and for the remaining 14 days of the study, the diabetic rats (a) started to drink 5% EtOH in place of water, (b) received a single daily 2.4 mM/kg oral dose of TAU or (c) were allowed to drink 5% EtOH after receiving a dose of TAU. Starting from day 28 and ending on day 29, a 24 h urine sample was collected, its volume was measured, and then used to measure glucose (GLC), total protein (TP) and electrolytes (Na+, K+, Ca++, Mg++). Blood samples collected immediately thereafter via cardiac puncture were processed for the plasma fractions which were analyzed for their creatinine (CRT) and urea nitrogen (UN) contents. In comparison to normal (control) rats, diabetic ones showed a higher output of urine (+5.6-fold), a massive increase in plasma GLC (+473%), passed more GLC (+73.8-fold) and TP (+8.2-fold) in the urine, showed higher plasma CRT (+241%) and UN (+74%) levels, a lower plasma UN/CRT ratio (-47%) and a greater output of electrolytes in the urine (by at least twofold). By themselves both EtOH and TAU were found to markedly lower the effects of diabetes, with EtOH generally appearing more effective than TAU. However, the concurrent availability of EtOH and TAU was found to be more protective than either treatment alone.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/farmacologia , Nefropatias/tratamento farmacológico , Taurina/farmacologia , Animais , Glicemia , Diabetes Mellitus Experimental/complicações , Nefropatias/etiologia , Masculino , Ratos , Ratos Sprague-Dawley , Urinálise
9.
Adv Exp Med Biol ; 1155: 497-505, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468426

RESUMO

Taurine (2-aminoethanesulfonic acid) is a sulfur-containing organic acid possessing several important effects, including antioxidant and anti-inflammatory ones. Exposure to ionizing radiation generates free radicals and reactive oxygen species (ROS) in irradiated cells, and free radical generation leads to oxidative stress. It is known that radiation nephropathy includes an inflammation-based process in which ROS and cytokines are responsible. Different doses of explored radiation can cause apoptosis, inflammation and a profound oxidative stress in kidneys. Oxidative stress is involved in renal injury after exposure to both ionizing radiation and inflammation. In this review, we describe the protective effect of taurine against several kidney diseases and the potential effects of taurine in the mitigation of radiation nephropathy. We also report that X-irradiation decreased the expression of taurine and TauT in the kidney. Taurine administration suppressed the decrease in the expression of taurine and TauT in the kidney after radiation exposure. Taurine might contribute to the mitigation of kidney injury induced by radiation.


Assuntos
Nefropatias/tratamento farmacológico , Lesões por Radiação/tratamento farmacológico , Taurina/farmacologia , Humanos , Rim/efeitos dos fármacos , Rim/efeitos da radiação , Nefropatias/fisiopatologia , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Estresse Oxidativo , Radiação Ionizante , Espécies Reativas de Oxigênio
10.
G Ital Nefrol ; 36(4)2019 Jul 24.
Artigo em Italiano | MEDLINE | ID: mdl-31373466

RESUMO

Fabry disease is a rare inborn error of the enzyme α-galactosidase (Α-Gal) and results in lysosomal substrate accumulation in tissues with a wide range of clinical presentations. The disease has attracted a lot of interest over the last years and several issues has been discovered up to now leading to increasing knowledge and awareness of the disease. However, several aspects are still unclear and under investigation. Thus, the new challenges that physicians encounter are the discovering of the pathogenic mechanisms, the neutralising antibodies to ERT, the long-term efficacy of therapies. In this article, we summarise and review the latest developments in the science community regarding diagnosis, management and monitoring of Fabry disease concerning in particular its physiopathology, novel biomarkers, antibodies development and novel treatment options.


Assuntos
Doença de Fabry/complicações , Nefropatias/etiologia , 1-Desoxinojirimicina/análogos & derivados , 1-Desoxinojirimicina/uso terapêutico , Progressão da Doença , Terapia de Reposição de Enzimas , Doença de Fabry/diagnóstico , Doença de Fabry/tratamento farmacológico , Doença de Fabry/genética , Feminino , Glomerulosclerose Segmentar e Focal/etiologia , Glicolipídeos/metabolismo , Heterozigoto , Humanos , Isoenzimas/imunologia , Isoenzimas/uso terapêutico , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Nefropatias/metabolismo , Masculino , Estresse Oxidativo , Podócitos/metabolismo , Podócitos/patologia , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/uso terapêutico , Fatores Sexuais , Esfingolipídeos/metabolismo , Triexosilceramidas/metabolismo , alfa-Galactosidase/imunologia , alfa-Galactosidase/uso terapêutico
11.
Environ Toxicol ; 34(12): 1277-1284, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31392797

RESUMO

Ethephon (2-chloroethyl phosphonic acid) is a plant growth promoter used to control the plant growth process by liberating ethylene and stimulating the production of endogenous ethylene. Medicinal plants are sources of novel drug discovery targets. Costus (Saussurea lappa) has been used as traditional Chinese medicine. The current study was conducted to examine the possible modifying effects of costus (S. lappa) root aqueous extract against kidney toxicity induced by ethephon in male rats. A total of 50 adult male rats were divided into five groups (first, control; second, costus; third, ethephon; fourth, posttreated ethephon with costus; fifth, ethephon self-healing). There is a significant increase in the serum levels of urea, creatinine, potassium ions, chloride ions, kidney injury, DNA damage, and proliferating cell nuclear antigen expressions in treated rats with ethephon when compared to the control group. In contrast, the treated rats with ethephon revealed a significant decrease in the levels of sodium ions and an insignificant decrease in the calcium ions. Saussurea lappa extract modified these alterations when compared to the control group. As a result, costus root extract significantly reduced rat kidney toxicity after ethephon administration. We recommend costus to be included in diet for its valuable effects, and also producers and consumers should become more aware about the toxic effects of ethephon.


Assuntos
Dano ao DNA/efeitos dos fármacos , Compostos Organofosforados/toxicidade , Saussurea/química , Animais , Creatinina/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Masculino , Medicina Tradicional Chinesa , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas/química , Raízes de Plantas/metabolismo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-Dawley , Saussurea/metabolismo , Ureia/sangue , Água/química
12.
Nutrients ; 11(7)2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31319485

RESUMO

Different diseases and disorders that affect the kidneys include, but are not limited to, glomerulonephritis, diabetic nephropathy, polycystic kidney disease, kidney stones, renal fibrosis, sepsis, and renal cell carcinoma. Kidney disease tends to develop over many years, making it difficult to identify until much later when kidney function is severely impaired and undergoing kidney failure. Although conservative care, symptom management, medication, dialysis, transplantation, and aggressive renal cancer therapy are some of the current strategies/approaches to kidney disease treatment, new preventative targeted therapies are needed. Epidemiological studies have suggested that a diet rich in fruits and vegetables is associated with health benefits including protection against kidney disease and renal cancer. Resveratrol, a polyphenol found in grapes and berries, has been reported to have antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, neuroprotective, and anti-cancer properties. The current review summarizes the existing in vitro and in vivo animal and human studies examining the nephroprotective effects of resveratrol.


Assuntos
Antioxidantes/uso terapêutico , Nefropatias/tratamento farmacológico , Resveratrol/uso terapêutico , Humanos
13.
BMC Res Notes ; 12(1): 385, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286995

RESUMO

OBJECTIVE: We take advantage of a rare occurrence when two different studies report on the estimation of quality of life utilities for the same health states to assess convergence of the reported measures. Health state utilities are important inputs into health economic models that estimate the impact of new medical technologies using a common metric of health gain-the quality adjusted life-year. RESULTS: We find low concordance between the two measures which is concerning in that this could have important ramifications for health care decision making based on estimated cost-effectiveness. We explore possible reasons for the discrepancy between the two measures and draw implications for the design of future studies.


Assuntos
Nível de Saúde , Nefropatias/tratamento farmacológico , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Análise Custo-Benefício , Humanos , Nefropatias/diagnóstico , Modelos Econômicos
14.
Artigo em Inglês | MEDLINE | ID: mdl-31280244

RESUMO

Background Doxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups. Methods Group 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20). Results The results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells. Conclusions This study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.


Assuntos
Doxorrubicina/efeitos adversos , Hidroxibenzoatos/farmacologia , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Animais , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Creatinina/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Malondialdeído/metabolismo , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo
15.
Int J Mol Sci ; 20(15)2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31357410

RESUMO

Kidney-yang deficiency syndrome (KYDS) is a metabolic disease caused by a neuro-endocrine disorder. The You-gui pill (YGP) is a classic traditional Chinese medicine (TCM) formula for the treatment of KYDS and has been widely used to warm and recuperate KYDS clinically for hundreds of years in China. However, it is unknown whetherthe corresponding targets and metabolic pathways can also be found via using metabonomics based on one platform (e.g., 1H NMR) to study different biological samples of KYDS. At the same time, relevant reports on further molecular verification (e.g., RT-qPCR analysis) of these targets associated with biomarkers and metabolic pathways have not yet, to our knowledge, been seen in KYDS's research. In the present study, a comprehensive strategy integrating systems pharmacology and 1H NMR-based urinary metabonomics analysis was proposed to identify the target proteins and metabolic pathways that YGP acts on KYDS. Thereafter, further validation of target proteins in kidney tissue was performed through quantitative real-time PCR analysis (RT-qPCR). Furthermore, biochemical parameters and histopathological analysis were studied. As a result, seven target proteins (L-serine dehydratase; phosphoenolpyruvate carboxykinase; spermidine synthase; tyrosyl-tRNA synthetase, glutamine synthetase; 3-hydroxyacyl-CoA dehydrogenase; glycine amidinotransferase) in YGP were discovered to play a therapeutic role in KYDS via affecting eight metabolic pathways (glycine, serine and threonine metabolism; butanoate metabolism; TCA cycle, etc.). Importantly, three target proteins (i.e., 3-hydroxyacyl-CoA dehydrogenase; glutamine synthetase; and glycine amidinotransferase) and two metabolic pathways (butanoate metabolism and dicarboxylate metabolism) related to KYDS, to our knowledge, had been newly discovered in our study. The mechanism of action mainly involved energy metabolism, oxidative stress, ammonia metabolism, amino acid metabolism, and fatty acid metabolism. In short, our study demonstrated that targets and metabolic pathways for the treatment of KYDS by YGP can be effectively found via combining with systems pharmacology and urinary metabonomics. In addition to this, common and specific targets and metabolic pathways of KYDS treated by YGP can be found effectively by integration with the analysis of different biological samples (e.g., serum, urine, feces, and tissue). It is; therefore, important that this laid the foundation for deeper mechanism research and drug-targeted therapy of KYDS in future.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Nefropatias/etiologia , Nefropatias/metabolismo , Redes e Vias Metabólicas/efeitos dos fármacos , Deficiência da Energia Yang/etiologia , Deficiência da Energia Yang/metabolismo , Animais , Biomarcadores , Biópsia , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Nefropatias/diagnóstico , Nefropatias/tratamento farmacológico , Espectroscopia de Ressonância Magnética , Masculino , Metaboloma , Metabolômica/métodos , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Biologia de Sistemas/métodos , Deficiência da Energia Yang/diagnóstico , Deficiência da Energia Yang/tratamento farmacológico
16.
Food Funct ; 10(6): 3782-3797, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31180394

RESUMO

Quercetin is the most ubiquitous flavonoid in fruits, herbs, vegetables and products made from them. It shows the potential to inhibit the progression of kidney fibrosis and the epithelial to mesenchymal transition (EMT) of the renal tubular system, but the molecular mechanism behind this is still not known. In our study, we explored the effect of quercetin treatment on extracellular matrix (ECM) deposition and stimulation of the EMT in vitro and in vivo and tried to deduce the mechanisms regulating these effects. In rats having unilateral ureter obstruction (UUO), quercetin treatment significantly prevented renal function decline. Quercetin reduced the TGF-ß1 expression and inhibited the epithelial cell to mesenchymal cell phenotypic switch, as well as ECM deposition in rats with UUO. In cultured epithelial cells of the renal tubular region (NRK-52E), quercetin markedly ameliorated the EMT and ECM synthesis induced by TGF-ß1. Activation of the Hedgehog pathway was closely related to EMT induction. Quercetin effectively suppressed the hyperactive Hedgehog pathway in NRK-52E cells treated with TGF-ß1 and in kidney obstructed rats, which reduced the EMT, ECM deposition and cellular proliferation. Moreover, we examined certain transcriptional factors (slug, snail, ZEB-1 and twist) that govern the E-cadherin expression at the level of transcription. The results unveiled that the four transcriptional factors were highly repressed in NRK-52E cells treated with TGF-ß1 and also in obstructed kidneys by quercetin-mediated inhibition. Therefore, these outcomes indicate that quercetin could alleviate fibrosis and the EMT in vitro and in vivo by inhibiting the activation of Hedgehog signaling and could act as a therapeutic agent for patients having several kinds of renal fibrotic diseases.


Assuntos
Transição Epitelial-Mesenquimal/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Nefropatias/tratamento farmacológico , Túbulos Renais/metabolismo , Quercetina/administração & dosagem , Animais , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Fibrose , Proteínas Hedgehog/genética , Humanos , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/fisiopatologia , Túbulos Renais/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
17.
J Pharm Pharmacol ; 71(8): 1301-1310, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215034

RESUMO

OBJECTIVES: The present study investigated the effects of atorvastatin on kidney injury in mice with pulmonary fibrosis (PF). METHODS: Adult mice were divided into four groups: mice treated with intratracheal bleomycin (I) and their controls (II), and mice treated with atorvastatin for 10 days after 7 days from bleomycin treatment (III) and their controls (IV). Mice were dissected on the 21st day. KEY FINDINGS: Mononuclear cell infiltrations, injured proximal tubule epithelium and p-c-Jun level increased, while cell proliferation and the levels of p-SMAD2, ELK1, p-ELK1, p-ATF2 and c-Jun decreased in the kidney tissue of mice with PF. The atorvastatin treatments to mice with PF resulted in significant increases at the TGF-ß activation, cell proliferation and kidney damage and decreases in the levels of p-SMAD2, p-ELK1, p-ATF2 and p-c-Jun, but not change the p-SMAD3, ELK1 and ATF2 in kidneys. CONCLUSIONS: The depletion of MAPK signals, rather than SMAD signalling, is effective in kidney damage of mice with PF. Atorvastatin did not regress kidney damage in these mice, whereas it increases the kidney injury. The c-Jun-mediated JNK signals could help kidney repair through cell proliferation. The treatment time and doses of atorvastatin should be optimized for regression of kidney damage.


Assuntos
Atorvastatina/farmacologia , Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Fibrose Pulmonar/metabolismo , Animais , Bleomicina/farmacologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais/efeitos dos fármacos
18.
Phytother Res ; 33(8): 2023-2033, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31215078

RESUMO

Unilateral ureteral obstruction (UUO) causes severe renal tubulointerstitial fibrosis. Because of many pharmacologic properties of thymoquinone (TQ), in this study, the effects of TQ against kidney fibrosis and dysfunction were investigated in rats with UUO. Forty male Wistar rats were divided into five groups: Sham operated, UUO, and the animals with UUO treated with losartan, captopril, or TQ. Collagen IV and transforming growth factor (TGF)-ß1 expressions, interstitial fibrosis, histological changes, and kidney function were assessed. UUO markedly increased renal expression of TGF-ß1 and collagen I and induced interstitial fibrosis (p < .001). Losartan, captopril, or TQ significantly downregulated the expression of these fibrotic markers and interstitial fibrosis (p < .01-p < .001). In UUO group, serum levels of urea and creatinine and protein excretion rate significantly increased, but glomerular filtration rate (GFR) and urine osmolarity showed a significant decrease (p < .001-p < .05). Administration of captopril and TQ caused no significant change in serum urea and protein excretion rate. Unlike losartan and captopril, TQ caused no significant alteration in GFR compared with Day 1. Losartan caused significant increases in serum urea and creatinine but significant decrease in urine osmolarity. TQ could be regarded as a potent therapeutic agent for treatment of UUO-induced kidney fibrosis and dysfunction.


Assuntos
Benzoquinonas/uso terapêutico , Fibrose/tratamento farmacológico , Nefropatias/tratamento farmacológico , Túbulos Renais/efeitos dos fármacos , Rim/efeitos dos fármacos , Obstrução Ureteral/tratamento farmacológico , Animais , Benzoquinonas/farmacologia , Rim/patologia , Nefropatias/patologia , Testes de Função Renal/métodos , Masculino , Ratos , Ratos Wistar
19.
Phytother Res ; 33(8): 2044-2055, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31209937

RESUMO

Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Células Epiteliais/metabolismo , Nefropatias/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Morus/química , NADPH Oxidases/metabolismo , Folhas de Planta/química , Espécies Reativas de Oxigênio/metabolismo , Transição Epitelial-Mesenquimal , Humanos , Nefropatias/patologia
20.
Int. j. morphol ; 37(2): 438-447, June 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1002240

RESUMO

Obesity is a modifiable risk factor for the development and progression of kidney disease. Obesity may harm kidneys in individuals without hypertension, diabetes, or pre-existing renal disease. Ginger, Zingiber officinale, has many beneficial pharmaceutical benefits. This study aimed to evaluate the Zingiber officinale protective effect against obesity complications which induced by high fat diet and caused renal dysfunctions. The study period was two months, and the experimental animals' groups were four, 80 Wistar rats were appropriated similarly 20 animals/group: control group; ginger extract group (GE); high-fat diet (HFD); and GE+HFD group. Body and fat weight, creatinine, leptin, TNF-α, total antioxidants, renal histopathological and ultrastructure were investigated. Rats in group of HFD showed a significant increase (P<0.05) in the body and fat weights, creatinine, leptin and TNF-α, and significant decrease (P<0.05) in total antioxidants (TAS). Ginger administration significantly showed the protective restoring the altered parameters. Furthermore, rats co-treated with ginger extract improved the histopathological and ultrastructural renal injury induced by obesity. The study concluded that the ginger extract used could suppress and decrease the renal damage induced by high-fat diet as it possesses potential medicinal values.


La obesidad es un factor de riesgo modificable para el desarrollo y la progresión de la enfermedad renal. La obesidad puede dañar los riñones en personas sin hipertensión, diabetes o enfermedad renal preexistente. El jengibre, Zingiber officinale, tiene muchos beneficios farmacéuticos. Este estudio tuvo como objetivo evaluar el efecto protector de Zingiber officinale en las complicaciones de la obesidad inducida por una dieta alta en grasas y las enfermedad renal. El período de estudio fue de dos meses, y los grupos de animales experimentales fueron cuatro, se asignaron 80 ratas Wistar de manera similar, 20 animales por grupo: grupo de control; grupo de extracto de jengibre (GE); dieta alta en grasas (DAG); y el grupo GE + DAG. Se evaluó el peso corporal y la grasa, creatinina, leptina, TNF-α, antioxidantes totales, histopatología renal y ultraestructura. Las ratas en el grupo de DAG mostraron un aumento significativo (P<0,05) en el peso corporal y de grasa, creatinina, leptina y TNF-a, y una disminución significativa (P<0,05) en los antioxidantes totales. La administración de jengibre mostró una protección significativa restaurando los parámetros alterados. Además, las ratas tratadas conjuntamente con extracto de jengibre mejoraron la lesión renal histopatológica y ultraestructural inducida por la obesidad. El estudio concluyó que el extracto de jengibre podría suprimir y disminuir el daño renal inducido por la dieta alta en grasas, ya que posee potenciales valores medicinales.


Assuntos
Animais , Ratos , Extratos Vegetais/farmacologia , Gengibre/química , Dieta Hiperlipídica/efeitos adversos , Nefropatias/tratamento farmacológico , Obesidade/complicações , Peso Corporal , Fator de Necrose Tumoral alfa/análise , Ratos Sprague-Dawley , Creatinina/análise , Leptina/análise , Microscopia Eletrônica de Transmissão , Rim/patologia , Nefropatias/patologia
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