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1.
Artículo en Chino | MEDLINE | ID: mdl-34074075

RESUMEN

Objective: To analyze the clinical characteristics of pesticide poisoning patients and explore the risk factors of acute kidney injury (AKI) . Methods: In September 2020, the clinical data of 155 patients with pesticide poisoning in the department of nephropathy, the Affiliated Hospital of Southwest Medical University from September 2018 to August 2020 were retrospectively analyzed. The patients were divided into AKI group (44 cases) and non AKI group (111 cases) according to the occurrence of AKI. The clinical characteristics, organ or system involvement and auxiliary examination results of the two groups were analyzed. Logistic regression was used to analyze the risk factors of AKI in patients with pesticide poisoning. Results: The types of pesticides causing poisoning mainly included herbicides, insecticides and biochemical pesticides. Compared with non AKI group, patients in AKI group had higher proportion of blood purification treatment and ICU monitoring treatment (P<0.05) , and were more likely to be complicated with acute respiratory failure, pulmonary fibrosis, myocardial injury, multiple organ dysfunction syndrome (MODS) , acute pancreatitis and coagulation abnormalities (P<0.05) . The mortality of AKI group (18.2%, 8/14) was significantly higher than that of non AKI group (0.9%, 1/111) (P<0.05) . Univariate analysis showed that the time from poisoning to treatment > 6 h, high WBC count, neutrophil count, alanine aminotransferase, aspartate aminotransferase, high sensitive troponin T, myoglobin and creatine kinase isoenzyme were the risk factors of AKI in patients with pesticide poisoning (P<0.05) . Multivariate logistic regression analysis showed that the time from poisoning to treatment >6 h was an independent risk factor for AKI in patients with pesticide poisoning (P<0.05) . Conclusion: The mortality of AKI secondary to pesticide poisoning is high. Attention should be paid to the time from poisoning to treatment, inflammatory state and changes of liver and myocardial function.


Asunto(s)
Lesión Renal Aguda , Pancreatitis , Plaguicidas , Enfermedad Aguda , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
2.
Medicine (Baltimore) ; 100(21): e26147, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-34032768

RESUMEN

INTRODUCTION: Acyclovir (ACV)-associated encephalopathy is related to an increase in plasma levels of 9-carboxymethoxymethylguanine, an ACV metabolite, and is often reported in patients with renal dysfunction. We report a case of ACV-associated encephalopathy with rapid progression of renal dysfunction after oral administration of valacyclovir (VACV) and review literature of previous ACV-associated encephalopathy cases. PATIENT CONCERNS: An 88-year-old man was diagnosed with herpes zoster. VACV (3000 mg/day) treatment was initiated. Serum creatinine (Cr) level was 0.80 mg/dL. However, irritability, memory impairment, and decreased responsiveness occurred after 3 days. The Cr level was 6.76 mg/dL on admission. DIAGNOSIS: He was diagnosed with ACV-associated encephalopathy with acute kidney injury. INTERVENTIONS: VACV was discontinued, hemodialysis was initiated on the day of admission, and then the signs and symptoms improved approximately 72 hours after the admission. CONCLUSION: Worsening of renal function and encephalopathy should be a focus when using VACV or ACV, regardless of age and original renal function. Acute kidney injury and ACV-associated encephalopathy may particularly occur in the elderly even when renal function is normal. Therefore, regular monitoring of renal function and consciousness is necessary during VACV treatment.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Antivirales/efectos adversos , Encefalopatías/inducido químicamente , Herpes Zóster/tratamiento farmacológico , Valaciclovir/efectos adversos , Lesión Renal Aguda/terapia , Anciano de 80 o más Años , Creatinina/sangre , Guanina/análogos & derivados , Guanina/sangre , Herpes Zóster/sangre , Herpes Zóster/fisiopatología , Humanos , Riñón/fisiología , Masculino , Valores de Referencia , Diálisis Renal
3.
Nihon Shokakibyo Gakkai Zasshi ; 118(5): 473-479, 2021.
Artículo en Japonés | MEDLINE | ID: mdl-33967132

RESUMEN

A male patient in his sixties with a long-term history of schizophrenia had been received glycerin enema once or twice a week in a mental hospital. He was emergently transferred to our hospital due to fever, vomiting, hematuria, and dyspnea. Laboratory findings on admission showed an elevation of white blood cells indicating inflammation, hemolysis, and renal dysfunction. Plain CT showed pleural effusion and ascites, elevated levels of perirectal fat, in addition to extraintestinal gas. Based on these findings, he was diagnosed with rectal damage caused by the glycerin enema and associated hemolysis with acute renal failure. He was kept under conditions of nil by mouth and received intravenous antibiotics, diuretic drug, and haptoglobin. Eventually, his condition improved with these conservative therapies. In this case, it is assumed that the hemolysis was caused by the influx of glycerin in the cytoplasm and an increase of osmotic pressure. Care should be taken during glycerin enema, which is widely used in daily practice as well as in home care settings.


Asunto(s)
Lesión Renal Aguda , Derrame Pleural , Lesión Renal Aguda/inducido químicamente , Enema/efectos adversos , Glicerol , Hemólisis , Humanos , Masculino
5.
Am J Case Rep ; 22: e931319, 2021 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-33888675

RESUMEN

BACKGROUND Acetazolamide (ACTZ) is commonly used in the prevention and treatment of various clinical conditions, and anuric acute kidney injury (AKI) is one of its known life-threatening complications. CASE REPORT We hereby report the case of a middle-aged man known to have compensated heart failure and hypertension with previously normal kidney function, who received a total dose of 2250mg of ACTZ over 3 days after cataract surgery. One week after the operation, he presented with anuria and severe bilateral renal colic, as well as progressively worsening kidney function and metabolic profile, which eventually required hemodialysis prior to recovery. CONCLUSIONS The cause of the AKI was attributed to intra-tubular obstruction by ACTZ-induced crystalluria, which required discontinuing the offending agent and dialysis to correct the kidney functions.


Asunto(s)
Lesión Renal Aguda , Anuria , Catarata , Acetazolamida/efectos adversos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/terapia , Anuria/inducido químicamente , Humanos , Masculino , Persona de Mediana Edad , Diálisis Renal
6.
BMJ Case Rep ; 14(4)2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827880

RESUMEN

A 77-year-old man was admitted with severe acute kidney injury and nephrotic syndrome. He was started on eltrombopag for chronic idiopathic thrombocytopenic purpura 6 weeks earlier. An ultrasound of the kidneys was normal and an auto-antibody screen was negative. The use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 5) between the patient's development of acute renal failure and eltrombopag therapy. Literature review identified only one other case of nephrotic syndrome and acute kidney injury associated with eltrombopag therapy in which a kidney biopsy revealed focal segmental glomerulosclerosis. Due to the challenges faced during the prevailing SARS-CoV-2 pandemic and persistent low platelet counts a renal biopsy was not undertaken. On stopping eltrombopag, the patients renal function stabilised and he successfully went into remission following treatment with high dose corticosteroids and diuretics. This report of a serious case of reversible renal failure and nephrotic syndrome after treatment with eltrombopag may serve to inform clinicians about the possible severe renal adverse effects of eltrombopag before its commencement for future use.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Benzoatos/efectos adversos , Hidrazinas/efectos adversos , Síndrome Nefrótico/inducido químicamente , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/efectos adversos , Corticoesteroides/uso terapéutico , Anciano , Humanos , Riñón/efectos de los fármacos , Masculino
7.
Georgian Med News ; (311): 156-162, 2021 Feb.
Artículo en Ruso | MEDLINE | ID: mdl-33814411

RESUMEN

Objective - to find out the possibility of using molecular hydrogen in the correction of no-reflow syndrome in the polyuric stage of acute kidney injury 72 hours after the administration of mercuric chloride in rats on a hyposodium diet. The experiments were performed on 60 male white non-linear sexually mature rats weighing 0.16-0.18 kg to study the effect of water loading with saturation with molecular hydrogen. Sublimate nephropathy was modeled under conditions of a hyposodium diet by subcutaneous injection of 0.1% mercury dichloride solution at a dosage of 5 mg/kg with a study after 72 hours, which corresponded to the early polyuric stage of acute kidney injury and the development of no-reflow syndrome. To saturate the water with molecular hydrogen at a concentration of 1.2 ppm and a redox potential from -100 to -350 mV, a new generation H2 generator Blue Water 900 (Korea) was used, containing an improved proton-exchange membrane PEM/SPE. Used: pathophysiological, biochemical, functional, chemiluminescent, statistical research methods. The antioxidant effect of loading with water with saturation with molecular hydrogen leads to a decrease in the loss of sodium ions due to an improvement in its reabsorption and ß2-microglobulin in the proximal tubule, a decrease in lipid peroxidation in the renal cortex was noted, the degree of its damage by an increase in the K+/Na+ ratio and a decrease in degree of edema. Improvement in the condition of the proximal nephron led to an increase in total, enzymatic fibrinolytic activity in the renal cortex. The increase in the activity of succinate dehydrogenase in the renal cortex is due to an increase in the delivery of electrons due to the negative redox potential and the selective antioxidant effect of molecular hydrogen. The anti-edema effect of molecular hydrogen was revealed at the level of 7 layers of the kidney. During the formation of the no-reflow syndrome in rats on a low-sodium diet 72 hours after the introduction of mercuric chloride, the possibility of breaking large and small vicious circles with an antioxidant solution of H2 was shown due to its high permeability and the ability to neutralize the hydroxyl radical and peroxynitrite.


Asunto(s)
Lesión Renal Aguda , Cloruro de Mercurio , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/metabolismo , Animales , Hidrógeno/metabolismo , Riñón/metabolismo , Peroxidación de Lípido , Masculino , Ratas
8.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-33801801

RESUMEN

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.


Asunto(s)
Lesión Renal Aguda/metabolismo , Biomarcadores/metabolismo , Exosomas/metabolismo , Inflamación/metabolismo , Proteómica/métodos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/orina , Adulto , Biomarcadores/orina , Cromatografía Liquida/métodos , Creatinina/orina , Humanos , Inflamación/orina , Masculino , Persona de Mediana Edad , Espectrometría de Masas en Tándem/métodos , Vancomicina/efectos adversos , Adulto Joven
9.
Semin Nephrol ; 41(1): 11-18, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33896468

RESUMEN

Opioid use and misuse in the United States has been at epidemic proportions and is predicted to increase further in the setting of the Coronavirus disease 19 pandemic. Acute kidney injury is a condition associated with significant morbidity and increased mortality. We review the literature on the effect of opioids on kidney function and critically examine the association between opioid use and acute kidney injury and identify at-risk populations in whom opioids should be used with caution. We also discuss the role of biomarkers in elucidating this condition and propose preventive measures, novel therapeutic options, and research directions.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Analgésicos Opioides/efectos adversos , Trastornos Relacionados con Opioides/complicaciones , Pandemias , Lesión Renal Aguda/epidemiología , Salud Global , Humanos , Incidencia , Trastornos Relacionados con Opioides/epidemiología
10.
Food Funct ; 12(7): 2985-2994, 2021 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-33704296

RESUMEN

C-Phycocyanin (CPC) exerts therapeutic, antioxidant, anti-inflammatory and immunomodulatory actions. It prevents oxidative stress and acute kidney damage caused by HgCl2. However, the exact mechanism of the pharmacological action of C-phycocyanin is as yet unclear. Some proposals express that CPC metabolism releases the active compound phycocyanobilin (PCB) that is able to induce CPC's therapeutical effects as an antioxidant, anti-inflammatory and nephroprotective. This study is aimed to demonstrate that PCB is the molecule responsible for C-phycocyanin's nephroprotective action in the acute kidney injury model caused by HgCl2. PCB was purified from C-phycocyanin and characterized by spectroscopy and mass spectrometry methods. Thirty-six male mice were administrated with 0.75, 1.5, or 3 mg per kg per d of PCB 30 min before the 5 mg kg-1 HgCl2 administration. PCB was administered during the following five days, after which the mice were euthanized. Kidneys were dissected to determine oxidative stress and redox environment markers, first-line antioxidant enzymes, effector caspase activities, and kidney damage markers.The quality of purified PCB was evaluated by spectroscopy and mass spectrometry. All PCB doses prevented alterations in oxidative stress markers, antioxidant enzymes, and caspase 9 activities. However, only the dose of 3 mg per kg per d PCB avoided the redox environment disturbance produced by mercury. All doses of PCB partially prevented the down-expression of nephrin and podocin with a consequent reduction in the damage score in a dose-effect manner. In conclusion, it was proven that phycocyanobilin is the molecule responsible for C-phycocyanin's nephroprotective action on acute kidney injury caused by mercury.


Asunto(s)
Lesión Renal Aguda/prevención & control , Ficobilinas/uso terapéutico , Ficocianina/uso terapéutico , Sustancias Protectoras/uso terapéutico , Lesión Renal Aguda/inducido químicamente , Animales , Modelos Animales de Enfermedad , Riñón/efectos de los fármacos , Masculino , Mercurio , Ratones , Ficobilinas/administración & dosificación , Ficobilinas/farmacología , Ficocianina/administración & dosificación , Ficocianina/farmacología , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Distribución Aleatoria
11.
Int J Cardiol ; 333: 83-89, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33662483

RESUMEN

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) can increase the mortality of patients undergoing transcatheter aortic valve replacement (TAVR) or percutaneous coronary intervention (PCI). The purpose of this paper was to compare the efficacy of the RenalGuard System and conventional hydration regimen in preventing CA-AKI in patients with TAVR or PCI. METHODS: We searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Clinical Trials (last updated July 11, 2020) for suitable reports. The primary outcome was the occurrence of CA-AKI. The secondary outcomes were renal replacement therapy (RRT), major cardiovascular events (MACEs), and other adverse complications. RESULTS: The search strategy yielded 270 studies (with data for 2067 participants). In the subgroup of PCI, low incidence of CA-AKI (6.7% vs 15.7%; 95%CI: 0.27 to 0.54; I2 = 8%; P < 0.00001) associate with RenalGuard group (RG) rather than control group (CG). Similarly, in the subgroup of TAVR, a low incidence of CA-AKI (15.6% vs 26.9%; 95%CI: 0.35 to 0.82; I2 = 88%; P = 0.004) relates to RG. However, this result is highly heterogeneous. Compare with conventional hydration, RenalGuard significantly reduce the incidence of pulmonary edema (1.5%vs4.1%; 95%CI: 0.18 to 0.72; I2 = 0%; P = 0.004). CONCLUSIONS: RenalGuard System can lessen the risk of CA-AKI and RRT in patients undergoing PCI. But for patients experiencing TAVR, due to unique hemodynamic effects, the role of RenalGuard remains questionable. RenalGuard is more secure than conventional hydration. Future work should elucidate the feasibility and safety of this prophylactic intervention in cardiac interventional therapy.


Asunto(s)
Lesión Renal Aguda , Intervención Coronaria Percutánea , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/prevención & control , Medios de Contraste/efectos adversos , Diuréticos , Humanos , Intervención Coronaria Percutánea/efectos adversos , Factores de Riesgo
12.
Phytomedicine ; 85: 153541, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33773190

RESUMEN

BACKGROUND: Acute kidney injury (AKI), characterised by excessive inflammatory cell recruitment and programmed cell death, has a high morbidity and mortality; however, effective and specific therapies for AKI are still lacking. OBJECTIVE: This study aimed to evaluate the renoprotective effects of gypenoside XLIX (Gyp XLIX) in AKI. METHODS: The protective effects of Gyp XLIX were tested in two AKI mouse models established using male C57BL/6 mice (aged 6-8 weeks) by a single intraperitoneal injection of cisplatin (20 mg/kg) or renal ischemia-reperfusion for 40 min. Gyp XLIX was administered intraperitoneally before cisplatin administration or renal ischemia-reperfusion. Renal function, tubular injury, renal inflammation and programmed cell death were evaluated. In addition, the renoprotective effects of Gyp XLIX were also evaluated in cisplatin- or hypoxia-treated tubular epithelial cells. The mechanisms underlying these effects were then explored using RNA sequencing. RESULTS: In vivo, Gyp XLIX substantially suppressed the increase in serum creatinine and blood urea nitrogen levels. Moreover, tubular damage was alleviated by Gyp XLIX as shown by periodic acid-Schiff staining, electron microscopy and molecular analysis of KIM-1. Consistently, we found that Gyp XLIX suppressed renal necroptosis though the RIPK1/RIPK3/MLKL pathway. The anti-inflammatory and antinecroptotic effects were further confirmed in vitro. Mechanistically, RNA sequencing showed that Gyp XLIX markedly suppressed the levels of IGF binding protein 7 (IGFBP7). Co-immunoprecipitation and western blot analysis further showed that Gyp XLIX reduced the binding of IGFBP7 to IGF1 receptor (IGF1R). Additionally, picropodophyllin, an inhibitor of IGF1R, abrogated the therapeutic effects of Gyp XLIX on cisplatin-induced renal cell injury; this finding indicated that Gyp XLIX may function by activating IGF1R-mediated downstream signalling Additionally, we also detected the metabolic distribution of Gyp XLIX after injection; Gyp XLIX had a high concentration in the kidney and exhibited a long retention time. These findings may shed light on the application of Gyp XLIX for AKI treatment clinically. CONCLUSION: Gyp XLIX may serve as a potential therapeutic agent for AKI treatment via IGFBP7/ IGF1R-dependent mechanisms.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Sustancias Protectoras/farmacología , Receptor IGF Tipo 1/metabolismo , Saponinas/farmacología , Lesión Renal Aguda/inducido químicamente , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Cisplatino , Humanos , Inflamación/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Necroptosis
13.
Anticancer Res ; 41(3): 1641-1646, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33788760

RESUMEN

BACKGROUND/AIM: Cisplatin increases the risk of acute kidney injury (AKI) during systemic chemotherapy. However, little is known about its risk of inducing AKI when used during intraperitoneal chemotherapy. This study aimed to determine the incidence of AKI in patients undergoing cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) with cisplatin. PATIENTS AND METHODS: A retrospective analysis of patients who received cisplatin-based HIPEC from November 2008 to March 2018 was undertaken to determine the incidence of AKI. RESULTS: A total of 111 patients were identified. The incidence of AKI was 15.3% (17/111). Univariate analysis showed increased peritoneal cancer index (PCI), low intraoperative and post-operative urine output were significantly associated with the development of AKI. Multivariate analyses did not identify any significant predictors factors for AKI. CONCLUSION: Cisplatin-based HIPEC is associated with AKI. At our centre, the incidence of AKI was 15.3%. Risk factors that may influence its development include high PCI and low perioperative diuresis.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Cisplatino/efectos adversos , /efectos adversos , Lesión Renal Aguda/epidemiología , Adulto , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
15.
Zhonghua Yi Xue Za Zhi ; 101(10): 727-731, 2021 Mar 16.
Artículo en Chino | MEDLINE | ID: mdl-33721952

RESUMEN

Objective: To explore the effects and mechanisms of Xuezhikang on preventing contrast-induced nephropathy (CIN) in diabetic rats. Methods: Streptozotocin (65 mg/kg) was injected intraperitoneally to establish a diabetes model in 7-week-old male Sprague-Dawley (SD) rats. After 4 weeks of modeling, 24 diabetic rats were randomly divided into 4 groups: sham group, CIN group, CIN+vehicle (Veh) group and Xuezhikang group. All animals were sacrificed at 24 hours after administration of contrast. Blood and kidney tissues were collected to detect biochemical, inflammation-related, oxidative stress-related and pathological indicators. Results: After administration of contrast agent, the renal function-related indicators were decreased in Xuezhikang group compared with CIN+Veh group [serum creatinine (SCr): (59.3±3.3) µmol/L vs (73.2±4.1) µmol/L; blood urea nitrogen (BUN): (13.8±0.5) mmol/L vs (16.3±0.6) mmol/L; serum neutrophil gelatinase-associated lipocalin (sNGAL): (41.4±2.0) ng/ml vs (54.9±4.4) ng/ml; urinary kidney injury moleculer-1 (uKIM-1): (11.1±0.5) ng/ml vs (16.6±0.5) ng/ml] (all P<0.05). Histological analysis showed that the severity of renal tubule dilatation, brush border loss and renal tubular cell necrosis in Xuezhikang group was better than that of CIN+Veh group. Additionally, the oxidative stress-related indicators of Xuezhikang group improved compared with those of CIN+Veh group [malondialdehyde (MDA): (12.1±0.7) nmol/mg vs (15.5±0.8) nmol/mg, superoxide dismutase (SOD): (35.0±2.2) U/mg vs (23.7±3.4) U/mg, renal nitrite: (1.7±0.1) nmol/mg vs (1.2±0.1) nmol/mg, all P<0.05]. Meanwhile, Xuezhikang pretreatment downregulated the mRNA and protein expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) (both P<0.05). Conclusion: The current study suggests that Xuezhikang protects against CIN in diabetic rats by inhibiting oxidative stress and inflammation.


Asunto(s)
Lesión Renal Aguda , Diabetes Mellitus Experimental , Medicamentos Herbarios Chinos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control , Animales , Medicamentos Herbarios Chinos/uso terapéutico , Riñón , Masculino , Ratas , Ratas Sprague-Dawley
16.
Toxicol Appl Pharmacol ; 418: 115492, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33722665

RESUMEN

Cisplatin is a commonly used anti-cancer drug, but it induces nephrotoxicity. As a water-soluble vitamin B family member, nicotinamide (NAM) was recently demonstrated to have beneficial effects for renal injury, but its underlying mechanism remains largely unclear. Here, we suggest that NAM may exert protective effects against cisplatin-induced acute kidney injury (AKI) mainly via suppressing the poly ADP-ribose polymerase 1 (PARP1)/p53 pathway. In our experiment, NAM protected against cisplatin-induced apoptosis both in cultured renal proximal tubular cells and AKI in mice. Mechanistically, NAM suppressed the expression and activation of p53, a known mediator of cisplatin-induced AKI. Upstream of p53, NAM attenuated the induction of γ-H2AX, a hallmark of DNA damage response. Interestingly, PARP1 was activated in cisplatin AKI and this activation was inhibited by NAM. Pharmacological inhibition of PARP1 with PJ34 significantly ameliorated p53 activation and cisplatin-induced cell death in RPTCs and AKI in mice. Thus, NAM may protect against cisplatin-induced AKI by suppressing the PARP1/p53 pathway.


Asunto(s)
Lesión Renal Aguda/prevención & control , Cisplatino , Túbulos Renales Proximales/efectos de los fármacos , Niacinamida/farmacología , Poli(ADP-Ribosa) Polimerasa-1/antagonistas & inhibidores , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/enzimología , Lesión Renal Aguda/patología , Animales , Apoptosis/efectos de los fármacos , Línea Celular , Modelos Animales de Enfermedad , Histonas/metabolismo , Túbulos Renales Proximales/enzimología , Túbulos Renales Proximales/patología , Masculino , Ratones Endogámicos C57BL , Fosfoproteínas/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Ratas , Transducción de Señal
17.
Mol Med Rep ; 23(5)2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33760157

RESUMEN

Diabetic nephropathy (DN) is a severe microvascular complication of diabetes. Hyperglycemia­induced glomerular mesangial cells injury is associated with microvascular damage, which is an important step in the development of DN. Piperazine ferulate (PF) has been reported to exert protective effects against the progression of DN. However, whether PF prevents high glucose (HG)­induced mesangial cell injury remains unknown. The aim of the present study was to investigate the effects of PF on HG­induced mesangial cell injury and to elucidate the underlying mechanisms. Protein and mRNA expression levels were determined via western blot analysis and reverse transcription­quantitative PCR, respectively. IL­6 and TNF­α levels were measured using ELISA. Reactive oxygen species levels and NF­κB p65 nuclear translation were determined via immunofluorescence analysis. Apoptosis was assessed by measuring lactate dehydrogenase (LDH) release, as well as using MTT and flow cytometric assays. The mitochondrial membrane potential of mesangial cells was determined using the JC­1 kit. The results revealed that LDH release were increased; however, cell viability and mitochondrial membrane potential were decreased in the HG group compared with the control group. These changes were inhibited after the mesangial cells were treated with PF. Moreover, PF significantly inhibited the HG­induced production of inflammatory cytokines and the activation of NF­κB in mesangial cells. PF also attenuated the HG­induced upregulation of the expression levels of fibronectin and collagen 4A1. Furthermore, the overexpression of p66Src homology/collagen (Shc) abolished the protective effect of PF on HG­induced mesangial cell injury. In vivo experiments revealed that PF inhibited the activation of inflammatory signaling pathways, glomerular cell apoptosis and mesangial matrix expansion in diabetic mice. Collectively, the present findings demonstrated that PF attenuated HG­induced mesangial cells injury by inhibiting p66Shc.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Nefropatías Diabéticas/tratamiento farmacológico , Piperazina/farmacología , Proteínas Represoras/genética , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/genética , Lesión Renal Aguda/patología , Animales , Colágeno Tipo IV/genética , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/patología , Modelos Animales de Enfermedad , Fibronectinas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Glucosa/toxicidad , Humanos , Hiperglucemia/complicaciones , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/genética , Hiperglucemia/patología , Interleucina-6/genética , Células Mesangiales/metabolismo , Células Mesangiales/patología , Ratones , ARN Mensajero/genética , Factor de Transcripción ReIA/genética , Factor de Necrosis Tumoral alfa/genética
18.
Life Sci ; 275: 119349, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33744325

RESUMEN

AIM: Gentamicin (GM) is an aminoglycoside antibiotic effectively used for severe/life-threatening infections. However, the clinical application of GM is limited by nephrotoxic side effects. Diosmin (DS) is a flavonoid with a wide range of bioactivities. However, its therapeutic potential in GM-induced nephrotoxicity remains unclear. METHODS: Rats received GM (100 mg/kg, i.p.) for 7 days either separately or in combination with oral DS (50 mg/kg). RESULTS: GM injection disrupted kidney function along with oxidant/antioxidant imbalance. Also, GM significantly decreased renal nuclear factor erythroid 2-related factor 2 (Nrf2), glutamyl cysteine synthetase (GCLC), heme oxygenase-1 (HO-1), superoxide dismutase3 (SOD-3), protein kinase B (AKT), and p-AKT expressions along with Kelch-like ECH-associated protein 1 (KEAP1) up-regulation. On the contrary, DS administration significantly attenuated GM-induced kidney dysfunction and restored kidney oxidant/antioxidant status. In addition, co-treatment with DS plus GM significantly enhanced Nrf2, GCLC, HO-1, SOD3, AKT, and p-AKT expressions along with KEAP1 down-regulation. Additionally, GM-treated rats exhibited a significant decrease in the expressions of renal peroxisome-proliferator activated receptor-gamma (PPAR-γ) and this reduction was alleviated by DS treatment. Furthermore, histopathological findings demonstrated that DS significantly reduced the GM-induced histological abrasions. Besides, an in-silico study was conducted to confirm our biochemical results. Interestingly, in-silico results strongly supported our biochemical investigation by studying the binding affinity of DS to KEAP1, AKT, and PPAR-γ proteins. SIGNIFICANCE: DS could be a promising protective agent against GM-induced nephrotoxicity through targeting of KEAP1/Nrf2/ARE, AKT, and PPAR-γ signaling pathways.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Diosmina/uso terapéutico , Gentamicinas/toxicidad , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Proteína Oncogénica v-akt/metabolismo , PPAR gamma/metabolismo , Transducción de Señal/efectos de los fármacos , Lesión Renal Aguda/patología , Lesión Renal Aguda/prevención & control , Animales , Western Blotting , Creatinina/sangre , Diosmina/farmacología , Riñón/efectos de los fármacos , Riñón/patología , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Ratas Wistar , Urea/sangre , Ácido Úrico/sangre
19.
Life Sci ; 275: 119387, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33774027

RESUMEN

Nephrotoxicity is a rapid deterioration of kidney function due to exposure to nephrotoxic drugs as gentamicin. Gentamicin increases the generation of reactive oxygen species (ROS) leading to inflammatory responses and nuclear factor-κB (NF-κB) activation. The renal renin-angiotensin system (RAS) is considered a crucial regulator for physiological homeostasis and disease progression through the classic ACE/Ang-II/AT1 axis and its antagonist, ACE2/Ang-(1-7)/Mas axis which exerts an important role in the kidney. The present study evaluates the protective effects of the angiotensin-converting enzyme 2 (ACE2) activator; xanthenone; against experimental nephrotoxicity induced by gentamicin. Rats were divided into 4 groups, normal control, xanthenone (2 mg/kg, s.c), gentamicin (100 mg/kg, i.p. for one week) and xanthenone + gentamicin groups. Blood urea nitrogen (BUN) and serum creatinine levels were measured. The kidney tissues were used for estimating glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), NF-κB, Angiotensin II (AngII), and Ang-(1-7). In addition, histopathological examination and Western blot analysis of ACE2 expression were done. Xanthenone significantly restored serum levels of BUN and creatinine. Xanthenone exerted significant antioxidant effect as revealed by increased GSH content and SOD activity together with reduced MDA content. It exerted anti-inflammatory effect by significant reduction in TNF-α, NF-κB and IL-6 expression compared to gentamicin group. Xanthenone increased Ang-(1-7) and ACE2 expression while significantly decreased Ang-II expression. Histopathologically, xanthenone markedly counteracted gentamicin-induced renal aberrations. Activation of ACE2/Ang-(1-7) by xanthenone produced significant antioxidant and anti-inflammatory effects that counteracted gentamicin-induced nephrotoxicity.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Angiotensina I/metabolismo , Gentamicinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fragmentos de Péptidos/metabolismo , Transducción de Señal/efectos de los fármacos , Xantonas/farmacología , Lesión Renal Aguda/prevención & control , Animales , Western Blotting , Interleucinas/metabolismo , Masculino , Ratas , Ratas Wistar
20.
Life Sci ; 276: 119420, 2021 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-33785340

RESUMEN

Quercetin (Q) is formulated into oil-in-water F127 microemulsions to improve its bioavailability. The size of the Q-loaded microemulsions system was about 8 nm by dynamic light scattering analysis. To compare antioxidant activity of bulk solution and microemulsion of Q, free radical scavenging activity was evaluated against 2,2-diphenyl-1-picrylhydrazyl (DPPH). The IC50 values were 56.77 and 187.68 µM, respectively. The drug in the bulk form released 16.34 times faster than microemulsion form. Although gentamicin (GM) has potent efficacy against gram-negative bacteria, it induces renal toxicity. Poor solubility and low bioavailability of Q as a bioflavonoid with potent antioxidant activity, limit its therapeutic application. We aimed to compare the effect of free Q and nanoencapsulated (NEQ) against GM-induced renal damage in Wistar rats. Forty-two animals were divided into six groups. Control and GM groups received apo-nanomicelles and GM (100 mg/kg) for 10 days. Two groups received Q (50 mg/kg, i.g.) and NEQ (50 mg/kg, i.g.) respectively for 10 days. Remaining two groups received Q and NEQ (50 mg/kg, i.g.) plus GM (100 mg/kg, i.p.) simultaneously for 10 days. After the experiments, serum and kidneys were used for biochemical, molecular and histological examinations. Immunohistochemical analysis was performed to explore kidney injury molecule-1 (KIM-1) expression as a specific protein biomarker of renal injury. Our findings indicated oxidative stress and altered histological features in renal tissue with deviated serum renal biomarkers in GM-treated rats. Although Q treatment in GM group tried to protect against GM-induced nephrotoxicity, but there were still differences compared to control rats. However, NEQ administration corrected elevations in the levels of urea, creatinine, uric acid and decrements in serum total proteins of GM group. Meanwhile, NEQ restored renal oxidative injury in GM rats through attenuation of lipid peroxidation and enhancement of antioxidant defense systems, glutathione, catalase and superoxide dismutase. NEQ could also normalize GM-induced abnormal renal histology features including fibrosis. Furthermore, the result of immunohistochemistry study confirmed these findings by undetecting KIM-1 expression in NEQ treated GM group, meanwhile showing this renal biomarker in GM and Q treated GM groups. Therefore, NEQ seems to be useful in protecting against renal oxidative stress and kidney damage in a rat model of GM nephrotoxicity which deserve further evaluations.


Asunto(s)
Lesión Renal Aguda/tratamiento farmacológico , Antioxidantes/farmacología , Gentamicinas/toxicidad , Polietilenos/química , Polipropilenos/química , Sustancias Protectoras/farmacología , Quercetina/farmacología , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Lesión Renal Aguda/patología , Animales , Antioxidantes/administración & dosificación , Antioxidantes/química , Biomarcadores/análisis , Nitrógeno de la Urea Sanguínea , Glutatión/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Masculino , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/química , Quercetina/administración & dosificación , Quercetina/química , Ratas , Ratas Wistar
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