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1.
Ecotoxicol Environ Saf ; 208: 111625, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33396145

RESUMO

Data for US adults aged ≥20 years from National Health and Nutrition Examination Survey for the years 2003-2014 were analyzed to evaluate how adjusted (N = 8481) and unadjusted (N = 9080) levels of selected perfluoroalkyl acids (PFAA) vary across the different stages of glomerular function (GF) among those who did not have diabetes, anemia, or albuminuria as compared to those who had diabetes only, anemia only, and albuminuria only. PFAAs selected for analyses were: perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorodecanoic acid (PFDA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Irrespective of GF stage, there was no noticeable evidence to suggest that adjusted levels of PFAA for those with diabetes only are any lower than those with no diabetes, no anemia, and no albuminuria. Those who had anemia only were found to have lower adjusted levels of at least PFOA, PFOS, PFDA, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. These results were seen in the presence (eGFR < 60 mL/min/1.73 m2) as well as the absence of chronic kidney disease. For GF-1 (eGFR > 90 mL/min/1.73 m2), GF-2 (60 ≤ eGFR ≤ 90 mL/min/1.73 m2), and GF-3B/4 (15 < eGFR ≤ 45 mL/min/1.73 m2), those who had albuminuria only had lower adjusted levels of PFOA, PFOS, and PFHxS than those who had no diabetes, no anemia, and no albuminuria. In general, adjusted levels of those who had albuminuria only were lower than those who had anemia only at GF-3 and more often than not at GF-1 and GF-2. Rise in adjusted levels of PFAA from GF-1 to GF-3A (45 < eGFR < 60 mL/min/1.73 m2) was faster for those with anemia only than any other comparison group for the total population and females.


Assuntos
Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Fluorcarbonetos/toxicidade , Rim/fisiologia , Adulto , Albuminúria/epidemiologia , Ácidos Alcanossulfônicos/toxicidade , Anemia/epidemiologia , Biomarcadores/metabolismo , Caprilatos/toxicidade , Ácidos Decanoicos/toxicidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Rim/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Ácidos Sulfônicos
3.
Kidney Int ; 99(1): 17-19, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33390226

RESUMO

Artificial intelligence (AI), and particularly deep learning (DL), are showing great potential in improving pathology diagnostics in many aspects, 1 of which is the segmentation of histology into (diagnostically) relevant compartments. Although most current studies focus on AI and DL in oncologic pathology, an increasing number of studies explore their application to nephropathology, including the study published in this issue of Kidney International by Jayapandian et al.


Assuntos
Inteligência Artificial , Aprendizado Profundo , Corantes , Rim , Córtex Renal
4.
Kidney Int ; 99(1): 24-26, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33390230

RESUMO

Early identification of kidney transplant recipients at risk of progressive allograft dysfunction may allow clinicians to provide closer monitoring and more aggressive risk factor modification. In this issue, Raynaud et al. presented a latent class model that clustered kidney transplant recipients into 8 risk categories of post-transplant kidney function loss. This commentary discusses some of the advantages, but also challenges, of the use of latent class analyses, including the clinical applicability of models that are often derived from such approaches.


Assuntos
Falência Renal Crônica , Transplante de Rim , Aloenxertos , Taxa de Filtração Glomerular , Humanos , Rim , Transplante de Rim/efeitos adversos
6.
Xenobiotica ; 51(1): 105-114, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32820679

RESUMO

Mycophenolic acid (MPA) has become a cornerstone of immunosuppressive therapy, in particular for transplant patients. In the gastrointestinal tract, the liver and the kidney, MPA is mainly metabolized into phenyl-ß-d glucuronide (MPAG). Knowledge about the interactions between MPA/MPAG and membrane transporters is still fragmented. The aim of the present study was to explore these interactions with the basolateral hepatic MRP4 transporter. The inhibition of the MRP4-driven transport by various drugs which can be concomitantly prescribed was also evaluated. In vitro experiments using vesicles overexpressing MRP4 showed an ATP-dependent transport of MPAG driven by MRP4 (Michaelis-Menten constant of 233.9 ± 32.8 µM). MPA was not effluxed by MRP4. MRP4-mediated transport of MPAG was inhibited (from -43% to -84%) by ibuprofen, cefazolin, cefotaxime and micafungin. An in silico approach based on molecular docking and molecular dynamics simulations rationalized the mode of binding of MPAG to MRP4. The presence of the glucuronide moiety in MPAG was highlighted as key, being prone to make electrostatic and H-bond interactions with specific residues of the MRP4 protein chamber. This explains why MPAG is a substrate of MRP4 whereas MPA is not.


Assuntos
Glucuronídeos/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Ácido Micofenólico/análogos & derivados , Transporte Biológico , Hepatócitos/metabolismo , Humanos , Rim/metabolismo , Fígado/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Simulação de Acoplamento Molecular , Ácido Micofenólico/metabolismo
7.
Xenobiotica ; 51(1): 95-104, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32544367

RESUMO

To date, relatively little is known about the interactions of pharmaceutical excipients with hepatic and renal drug uptake transporters. The present study was designed to systematically evaluate the effects of 16 commonly consumed excipients on human organic cation transporter 1 and 2 (hOCT1 and hOCT2), human organic anion transporter 1 and 3 (hOAT1 and hOAT3) and human organic anion transporting polypeptide 1B1 and 1B3 (hOATP1B1 and hOATP1B3). The inhibitory effects and mechanisms of excipients on transporters were investigated using in vitro uptake studies, cell viability assays, concentration-dependent studies, and the Lineweaver-Burk plot method. Triton X-100 is a non-competitive inhibitor for all six transporters. Tween 20 inhibits hOCT2, hOAT1, hOAT3, and hOATP1B3 in a mixed way, whereas it competitively inhibits hOATP1B1. The inhibition of Tween 80 is competitive for hOCT2, non-competitive for hOATP1B1 and hOATP1B3, and mixed for hOAT1 and hOAT3. Concentration-dependent studies identify Triton X-100 as a strong inhibitor of hOCT1 and hOCT2 with IC50 values of 20.1 and 4.54 µg/mL, respectively. Additionally, Triton X-100, Tween 20, and Tween 80 strongly inhibit hOAT3 with IC50 values ≤31.0 µg/mL. The present study is significant in understanding the excipient-drug interactions and provides valuable information for excipient selection in drug development.


Assuntos
Transporte Biológico/efeitos dos fármacos , Excipientes/farmacologia , Animais , Ânions/metabolismo , Cátions/metabolismo , Excipientes/metabolismo , Humanos , Rim/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Transportador 1 de Cátions Orgânicos/metabolismo , Transportador 2 de Cátion Orgânico/metabolismo
8.
Chem Biol Interact ; 333: 109307, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33159969

RESUMO

Renal ischemia-reperfusion injury (R-IRI) is the main cause of acute renal failure. Carvedilol has been shown to protect against R-IRI. However, the underlying mechanisms are still not completely clarified. This study aimed to investigate the role of lipid signaling in mediating carvedilol protective effects against R-IRI in insulin-resistant mice by using two different lipid signaling modulators, quercetin and lithium chloride (LiCl). Mice were fed high-fructose, high-fat diet (HFrHFD) for 16 weeks to induce insulin resistance. At the end of feeding period, mice were randomly distributed into five groups; Sham, R-IRI, Carvedilol (20 mg/kg, i.p.), Carvedilol + Quercetin (10 mg/kg, i.p.), Carvedilol + LiCl (200 mg/kg, i.p.). R-IRI was performed by applying 30 min of unilateral renal ischemia followed by one hour of reperfusion. Quercetin and LiCl were administered 30 min before carvedilol administration and carvedilol was administered 30 min before ischemia. Changes in kidney function tests, histopathology, fibrosis area, lipid signaling, inflammatory, apoptosis and oxidative stress markers in the kidney were measured. Results showed that R-IRI decreased kidney function, impaired renal tissue integrity, modulated lipid signaling and increased renal inflammation, apoptosis and oxidative stress. Carvedilol treatment decreased the detrimental effects induced by R-IRI. In addition, pre-injection of both quercetin and LiCl potentiated the reno-protective effects of carvedilol against R-IRI independent of changes in lipid mediators like phosphatidyl inositol 4,5 bisphosphate (PIP2) and diacylglycerol (DAG). In conclusion, quercetin and LiCl potentiate the protective effects of carvedilol against R-IRI in HFrHFD-fed mice by reducing inflammation and oxidative stress independent of lipid signaling.


Assuntos
Carvedilol/farmacologia , Dieta Hiperlipídica/efeitos adversos , Frutose/administração & dosagem , Rim/efeitos dos fármacos , Cloreto de Lítio/farmacologia , Quercetina/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Sinergismo Farmacológico , Rim/irrigação sanguínea , Rim/metabolismo , Rim/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Traumatismo por Reperfusão/induzido quimicamente , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais/efeitos dos fármacos
9.
Life Sci ; 264: 118656, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33121989

RESUMO

AIMS: Abnormal expression of long non-coding RNAs (lncRNAs) occurs in several diseases including renal fibrosis. Notably, growth arrest-specific 5 (Gas5) is a lncRNA, which functions as an essential modulator of cell proliferation and growth. However, the role and expression of lncRNA Gas5 associated with renal fibrosis remains controversial. Herein, we investigate the effect of lncRNA Gas5 deficiency in renal fibrosis induced by the operation of unilateral ureteric obstruction (UUO) in mice. MAIN METHODS: Sera and urine of mice were used to detect markers of renal function. Further, Masson and immunohistochemical staining, western blotting as well as qRT-PCR were performed to observe the distribution and expression of fibrosis marker in the kidney tissue of the mice. KEY FINDINGS: Unlike the wild type mice, the obstructed kidney in Gas5+/- mice showed more severe renal fibrosis and collagen deposition. In the UUO-Gas5+/- group, the serum levels of uric acid, serum creatinine, and the urine levels of albumin-to-creatinine ratio were higher. Moreover, the expression of mRNA and protein of α-smooth muscle actin (α-SMA), vimentin, collagen IV, fibronectin, and matrix metalloproteinase 9 (MMP9) were higher, whereas that of phosphatase and tensin homolog (PTEN) were lower with the difference being statistically significant (p < 0.05). SIGNIFICANCE: lncRNA Gas5 was up-regulated in renal fibrosis tissues, and its deficiency exacerbated renal fibrosis in the UUO mice model.


Assuntos
Rim/patologia , RNA Longo não Codificante/metabolismo , Obstrução Ureteral/genética , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Fibrose , Regulação da Expressão Gênica , Rim/fisiopatologia , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Obstrução Ureteral/fisiopatologia
10.
Ultrasonics ; 110: 106292, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33152656

RESUMO

Thermal strain imaging (TSI) is a promising technique for ultrasonic thermometry, especially in the applications of thermal therapies. The accuracy of TSI is dependent on the sampling rate and line density of B-Scan images, and the prevalent IQ-demodulated ultrasound data outputted from low- and middle-end machines are therefore insufficient. Here, the feasibility of using interpolated IQ images for TSI (based on the "infinitesimal echo strain filter" model) is studied through in vivo experiments targeting the perirenal fat of pigs. It is demonstrated that, axial interpolations, especially those using the zero-padding algorithm, can recover the capabilities of the low-sampling-rate complex IQ images in TSI, and make their performances comparable to those of RF/IQ complex images with higher sample rate. Meanwhile, interpolations along the lateral direction can increase the line density of IQ images, reduce TSI errors, and reveal more details in the temperature maps. In the experiments, the variation in the thermometry coefficient (the k-value) is well below 3%. The findings here bring down the requirement of high sampling rate as well as high line density of US images in TSI, making it possible to be applied on common US machines.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Rim/diagnóstico por imagem , Termografia/métodos , Ultrassonografia de Intervenção/métodos , Algoritmos , Animais , Temperatura Alta , Micro-Ondas , Estresse Mecânico , Suínos
11.
Toxicon ; 189: 65-72, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33227324

RESUMO

T-2 toxin is a common fungal toxin, which is not only widely found in wheat, barley, corn, and other food crops and their related products, but also in various animal feeds. Acrylamide (ACR) is mainly formed by the free amino acid, asparagine and reducing sugars, such as glucose and fructose, and is commonly found in potato chips, French fries, toast, coffee, and other foods. Therefore, people are highly likely to consume food via their daily diets that are contaminated with both T-2 toxin and ACR. Since liver and kidneys were possible toxic targets of both T-2 toxin and ACR, this study assessed whether combined exposure could increase hepatotoxicity and nephrotoxicity using both cell cultures and animal models. We used L02 and MARC-145 cells and treated with T-2 toxin (5-15 nM) and ACR (1-3 mM) alone or in combination with a fixed ratio of 1:200 (T-2 toxin/ACR). ACR (50 mg/kg, i.g., 5d) and T-2 toxin (5 mg/kg, i.g., 5d) were used to assess the biochemical, proteins and histplogical changes in C57BL/6N mice. Results showed the combination resulted in synergistic cytotoxicity in vitro, while significantly increasing liver and kidney toxicity in vivo. Mechanistically, T-2 toxin decreased Manganese superoxide dismutase expression, while ACR reduced catalase expression. These two mechanisms were converged in response to the combination, leading to enhanced oxidative stress generation. The findings highlighted the necessity to consider the combined toxicity during the safety assessment of these food-borne contaminants.


Assuntos
Acrilamida/toxicidade , Sinergismo Farmacológico , Toxina T-2/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas , Rim , Fígado , Camundongos , Mitocôndrias , Estresse Oxidativo
12.
Phytomedicine ; 80: 153374, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33075645

RESUMO

BACKGROUND: Insufficient renal urate excretion and/or overproduction of uric acid (UA) are the dominant causes of hyperuricemia. Baicalein (BAL) is widely distributed in dietary plants and has extensive biological activities, including antioxidative, anti-inflammatory and antihypertensive activities. PURPOSE: To investigate the anti-hyperuricemic effects of BAL and the underlying mechanisms in vitro and in vivo. METHODS: We investigated the inhibitory effects of BAL on GLUT9 and URAT1 in vitro through electrophysiological experiments and 14C-urate uptake assays. To evaluate the impact of BAL on serum and urine UA, the expression of GLUT9 and URAT1, and the activity of xanthine oxidase (XOD), we developed a mouse hyperuricemia model by potassium oxonate (PO) injection. Molecular docking analysis based on homology modeling was performed to explain the predominant efficacy of BAL compared with the other test compounds. RESULTS: BAL dose-dependently inhibited GLUT9 and URAT1 in a noncompetitive manner with IC50 values of 30.17 ± 8.68 µM and 31.56 ± 1.37 µM, respectively. BAL (200 mg/kg) significantly decreased serum UA and enhanced renal urate excretion in PO-induced hyperuricemic mice. Moreover, the expression of GLUT9 and URAT1 in the kidney was downregulated, and XOD activity in the serum and liver was suppressed. The docking analysis revealed that BAL potently interacted with Trp336, Asp462, Tyr71 and Gln328 of GLUT9 and Ser35 and Phe241 of URAT1. CONCLUSION: These results indicated that BAL exerts potent antihyperuricemic efects through renal UA excretal promotion and serum UA production. Thus, we propose that BAL may be a promising treatment for the prevention of hyperuricemia owing to its multitargeted inhibitory activity.


Assuntos
Flavanonas/farmacologia , Hiperuricemia/tratamento farmacológico , Ácido Úrico/urina , Xantina Oxidase/antagonistas & inibidores , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Inibidores Enzimáticos/farmacologia , Flavanonas/química , Flavanonas/metabolismo , Proteínas Facilitadoras de Transporte de Glucose/química , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Células HEK293 , Humanos , Hiperuricemia/induzido quimicamente , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Masculino , Camundongos , Simulação de Acoplamento Molecular , Transportadores de Ânions Orgânicos/química , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Proteínas de Transporte de Cátions Orgânicos/química , Proteínas de Transporte de Cátions Orgânicos/genética , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Ácido Oxônico/toxicidade , Ácido Úrico/sangue
13.
Environ Sci Pollut Res Int ; 28(2): 1619-1626, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32851527

RESUMO

Cadmium (Cd) as nephrotoxicant metal exerts its potent effect mainly on renal tubules disturbing its functions. A cross-sectional study was conducted on 55 sewage workers occupationally exposed to Cd and 50 control subjects. The study aimed to assess the effect of low-level Cd exposure on blood pressure and renal function in terms of serum cystatin-C levels. The associations between genetic polymorphisms of ACEI/D and ACE G2350A and hypertension and tubular injury among workers were studied. We analyzed blood and urine Cd concentration (U-Cd), serum cystatin-C, ACE I/D polymorphisms, and ACE G2350A, and blood pressure was measured. Results recorded a significant rise in serum and U-Cd and cystatin-C levels in sewage workers compared with controls. Significant distribution in genotype frequency of ACE I/D and ACE G2350A gene was detected. An association in DD genotype of ACE I/D with a rise in serum and U-Cd was observed in workers. In wild type genotype GG of ACE G2350A gene, a significant rise in serum cystatin-C levels and diastolic pressure was found while in heterozygote genotype GA significant rise in U-Cd levels was detected. Also, the association of AA genotype of ACE G2350A gene with a significant rise in serum and U-Cd and cystatin-C levels was shown among workers compared with control groups. Our findings indicated an association of ACE DD polymorphism in conjugation with GG genotype of ACE2 with hypertension and tubular injury in sewage workers.


Assuntos
Hipertensão , Esgotos , Estudos Transversais , Genótipo , Humanos , Hipertensão/genética , Rim , Peptidil Dipeptidase A/genética , Polimorfismo Genético
14.
Environ Sci Pollut Res Int ; 28(2): 1762-1774, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32856245

RESUMO

The current study aimed to investigate the protective effect of corn silk methanolic extract (CSME) against acetaminophen (APAP)-induced nephrotoxicity. The present study was carried out on 40 male Wistar albino rats, which were randomly divided into four groups (n = 10): control group, orally administered with a single dose of 1.8 ml 0.9% normal saline at the last day of the experiment; CSME group, orally received CSME (400 mg/kg BW daily for 5 weeks); APAP group, orally administered with a single dose of APAP (2 g/kg BW); and CSME and APAP group, orally administered with CSME, followed by a single oral dose of APAP. The results of this study revealed that APAP caused a significant increase in serum urea, creatinine concentrations, and malondialdehyde (MDA) concentrations in renal tissues. In addition, APAP caused a significant decrease in superoxide dismutase (SOD) and glutathione peroxidase (GPX) activities in renal tissues compared with the control group. Furthermore, APAP caused marked renal damage as revealed by alterations in histopathological architectures of kidney tissues. APAP resulted in a marked expression of caspase 3 and nuclear factor κB (NFĸß) within the renal tubules, while caused marked decrease of proliferating cell nuclear antigen (PCNA) immunostaining and transforming growth factor beta 1 (TGFß 1) expression within the epithelial lining of the renal tubules. However, pre-treatment with CSME returned all biochemical parameters, histopathological changes, and immunohistochemical parameters toward normal levels as the control group. In conclusion, oral administration of CSME protected rats against APAP renal toxicity through its antioxidant, anti-apoptotic, and anti-inflammatory protective mechanisms.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/metabolismo , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Estresse Oxidativo , Extratos Vegetais/metabolismo , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar , Seda/metabolismo , Zea mays
15.
Environ Sci Pollut Res Int ; 28(1): 936-946, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32827115

RESUMO

To explore the mechanism of renal toxicity induced by florfenicol (FFC), 120 chicks were randomly divided into 6 groups, 20 in each group. Except for the control group, different doses of FFC (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L, and 1.8 g/L) were added to drinking water in the other 5 groups. Five days later, blood was collected from the vein under the wing, and the complete kidneys were obtained as soon as possible, then tested the experimental indicators. The results showed that compared with control group, all doses of FFC significantly reduced the average weight gain of chicks (P < 0.05 or P < 0.01). Except for the 0.15 g/L FFC group, kidney index of chicks in the other doses of FFC groups were significantly increased (P < 0.05 or P < 0.01). The kidney tissues in all FFC groups showed obvious damage, deformities, cell atrophy, and cell gap enlargement. In addition, all doses of FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum, and malondialdehyde (MDA) in renal tissue (P < 0.05 or P < 0.01), but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) in renal tissue (P < 0.05 or P < 0.01). FFC significantly inhibited the mRNA and protein expression levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3, and Caspase-6 (P < 0.05 or P < 0.01). The apoptotic rate of renal cells in all doses of FFC groups increased significantly (P < 0.05 or P < 0.01). It was concluded that FFC had a certain degree of nephrotoxicity, and with the increase of FFC concentration, the kidney injury of chicks became more and more serious. FFC promoted oxidative stress response in kidney of chicks by inhibiting the expression of related factors in Nrf2-ARE pathway. Moreover, the expression of pro-apoptotic factors was upregulated to improve the apoptosis rate of renal cells, which resulted in excessive apoptosis of renal cells and seriously affected the kidney function of chicks.


Assuntos
Estresse Oxidativo , Tianfenicol , Animais , Apoptose , Rim/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Tianfenicol/análogos & derivados
16.
Transplantation ; 105(1): 206-211, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-32852403

RESUMO

BACKGROUND: There is compelling evidence that renal complications in a native kidney are a major concern in patients infected with severe acute respiratory syndrome coronavirus 2, the causal agent of coronavirus disease 2019 (COVID-19). The spectrum of renal lesions observed on renal grafts in this context remains to be determined. METHODS: We report the case of a renal transplant recipient with non-severe COVID-19, who subsequently developed nephrotic syndrome associated with acute renal injury. RESULTS: Renal biopsy demonstrated focal and segmental glomerulosclerosis lesions classified as not otherwise specified histological variant. Genotyping for 2 risk alleles of the apolipoprotein L1 gene demonstrated that the donor was homozygous for the G2/G2 genotype. CONCLUSIONS: In renal transplant patients receiving kidneys from donors with high-risk apolipoprotein L1 variants, COVID-19 may promote acute glomerular injury in the form of focal and segmental glomerulosclerosis.


Assuntos
Apolipoproteína L1/genética , Glomerulosclerose Segmentar e Focal/etiologia , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade
17.
Urol Clin North Am ; 48(1): 81-90, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33218596

RESUMO

Surgical techniques for robot-assisted partial nephrectomy are driven by the aims of simplifying the most challenging surgical steps, maximizing functional and oncologic outcomes, and consistently pushing the envelope on possibilities. Over the past several years, we have seen an emergence in not only innovation in surgical technique, and robotic platforms, but integration of a variety of imaging techniques. We believe with developing robotic expertise, practicing urologists will continue to push the envelope in nephron preservation and complication-free recovery.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Rim/cirurgia , Nefrectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Carcinoma de Células Renais/diagnóstico por imagem , Meios de Contraste , Humanos , Processamento de Imagem Assistida por Computador , Raios Infravermelhos , Rim/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Laparoscopia , Nefrectomia/tendências , Procedimentos Cirúrgicos Robóticos/tendências , Cirurgia Assistida por Computador , Ultrassonografia/métodos
18.
Ecotoxicol Environ Saf ; 207: 111282, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32949928

RESUMO

In order to study the effects and mechanism of florfenicol (FFC) on the kidney function of broilers, 180 1-day-old broilers were randomly divided into 6 groups, 30 in each group. Except for the control group, different doses of FFC were added to drinking water in the other 5 groups (0.15 g/L, 0.3 g/L, 0.6 g/L, 1.2 g/L and 1.8 g/L). After continuous administration for 5 days, renal histopathological changes, serum renal function indicators, renal peroxidation products and antioxidant factors, and apoptotic factors were detected in broilers aged 21 and 42 days. The results showed that compared with the control group, the kidney tissue structure was disordered, the glomerulus was atrophic, the cystic cavity was enlarged, and the epithelial cells of renal tubules were seriously vacuolated in broilers of treatment groups. And with the growth of broilers, the kidney injury of broilers in the low-dose FFC group was relieved. FFC significantly increased the contents of uric acid (UA), blood urea nitrogen (BUN), creatinine (CRE) in serum and malondialdehyde (MDA) in kidney of broilers, but significantly reduced the levels of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in kidney. FFC significantly inhibited the mRNA relative transcriptional levels of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase-1 (NQO-1), and increased the mRNA and protein expression levels of p53, Caspase-3 and Caspase-6 in kidney tissue of broilers. It is concluded that FFC has certain nephrotoxicity to broilers, and its effect on kidney is dose-dependent and reversible. FFC causes intense lipid peroxidation in broiler kidney by inhibiting the expression of related factors in the downstream signal pathway of Nrf2. FFC can also up-regulate the expression of pro-apoptotic factors and accelerate the abnormal apoptosis of renal cells, thus seriously affecting the renal function of broilers.


Assuntos
Apoptose/efeitos dos fármacos , Galinhas/metabolismo , Rim/efeitos dos fármacos , Peroxidação de Lipídeos/efeitos dos fármacos , Tianfenicol/análogos & derivados , Drogas Veterinárias/toxicidade , Animais , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Glutationa/metabolismo , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Masculino , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais , Tianfenicol/toxicidade
19.
Ecotoxicol Environ Saf ; 208: 111439, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33039874

RESUMO

Trichloroethylene (TCE) induced occupational medicamentosa-like dermatitis (OMLDT) in patients is accompanied, typically, by renal damage. But the role of C5b-9 and IL-1ß in TCE-sensitized mouse renal tubular damage is unclear. This study aimed to investigate whether TCE-sensitized mouse renal tubular epithelial cell damage was induced by NLRP3 inflammasome and whether NLRP3 inflammasome was activated by sublytic C5b-9. In total, 52 specific pathogen-free BALB/c female mice, 6- to 8-week-old, were used for establishing the TCE-sensitized mouse model. Renal tubular epithelial cells were isolated and used for determining the sublytic level of C5b-9. Kidney histological examination, serum neutrophil gelatinase associated lipocalin (NGAL) level were used for kidney damage evaluation. Renal protein levels of C5b-9, NLRP3, ASC, Caspase-1, IL-1ß, and IL-18 were measured. The renal lesions, serum NGAL level, renal NLRP3, ASC, Caspase-1 and IL-1ß protein levels all increased significantly in TCE sensitized positive group. However, pretreatment with recombinant protein sCD59-Cys inhibited the expression of C5b-9, NLRP3 inflammasome, IL-1ß, IL-18, and attenuated renal tubular epithelial cell damage. The sublytic C5b-9 activated NLRP3 inflammasome and aggravated renal tubular epithelial cell damage. Pretreatment with recombinant protein sCD59-Cys blocked the expression of the NLRP3 inflammasome by inhibiting the expression of C5b-9, and alleviating renal tubular epithelial cell damage.


Assuntos
Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Solventes/toxicidade , Tricloroetileno/toxicidade , Animais , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Feminino , Rim/metabolismo , Nefropatias/metabolismo , Lipocalina-2 , Camundongos , Camundongos Endogâmicos BALB C
20.
Ecotoxicol Environ Saf ; 208: 111475, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33068975

RESUMO

Cocaine is one of the most widely used illicit drugs in the world, and as a result of incomplete removal by sewage treatment plants it is found in surface waters, where it represents a new potential risk for aquatic organisms. In this study we evaluated the influence of environmental concentrations of cocaine on the liver and the kidney of the European eel (Anguilla anguilla). The eels were exposed to 20 ng L-1 of cocaine for fifty days, after which, three and ten days after the interruption of cocaine exposure their livers and kidneys were compared to controls. The general morphology of the two organs was evaluated, as well as the following parameters: cytochrome oxidase (COX) and caspase-3 activities, as markers of oxidative metabolism and apoptosis activation, respectively; glucose-regulated protein (GRP)78 levels, as a marker of endoplasmic reticulum (ER)-stress; blood glucose level, as stress marker; serum levels of alanine aminotransferase (ALT), as a marker of liver injury and serum levels of C-reactive protein (CRP), as a marker of the inflammatory process. The liver showed morphologic alterations such as necrotic areas, karyolysis and pyknotic nuclei, while the kidneys had dilated glomeruli and the renal tubules showed pyknotic nuclei and karyolysis. In the kidney, the alterations persisted after the interruption of cocaine exposure. In the liver, COX and caspase-3 activities increased (COX: P = 0.01; caspase-3: P = 0.032); ten days after the interruption of cocaine exposure, COX activity returned to control levels (P = 0.06) whereas caspase-3 activity decreased further (P = 0.012); GRP78 expression increased only in post-exposure recovery specimens (three days: P = 0.007 and ten days: P = 0.008 after the interruption of cocaine exposure, respectively). In the kidney, COX and caspase-3 activities increased (COX: P = 0.02; caspase-3: P = 0.019); after the interruption of cocaine exposure, COX activity remained high (three days: P = 0.02 and ten days: P = 0.029 after the interruption of cocaine exposure, respectively) whereas caspase-3 activity returned to control values (three days: P = 0.69 and ten days: P = 0.67 after the interruption of cocaine exposure, respectively). Blood glucose and serum ALT and CRP levels increased (blood glucose: P = 0.01; ALT: P = 0.001; CRP: 0.015) and remained high also ten days after the interruption of cocaine exposure (blood glucose: P = 0.009; ALT: P = 0.0031; CRP: 0.036). These results suggest that environmental cocaine concentrations adversely affected liver and kidney of this species.


Assuntos
Anguilla/fisiologia , Cocaína/toxicidade , Poluentes Químicos da Água/toxicidade , Alanina Transaminase/metabolismo , Anguilla/sangue , Animais , Glicemia , Proteína C-Reativa/metabolismo , Caspase 3/metabolismo , Cocaína/análise , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Drogas Ilícitas , Rim/metabolismo , Fígado/metabolismo
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