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1.
J Environ Sci (China) ; 124: 481-490, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36182156

RESUMO

Triclosan (TCS) is a ubiquitous antimicrobial used in daily consumer products. Previous reports have shown that TCS could induce hepatotoxicity, endocrine disruption, disturbance on immune function and impaired thyroid function. Kidney is critical in the elimination of toxins, while the effects of TCS on kidney have not yet been well-characterized. The aim of the present study was to investigate the effects of TCS exposure on kidney function and the possible underlying mechanisms in mice. Male C57BL/6 mice were orally exposed to TCS with the doses of 10 and 100 mg/(kg•day) for 13 weeks. TCS was dissolved in dimethyl sulfoxide (DMSO) and diluted by corn oil for exposure. Corn oil containing DMSO was used as vehicle control. Serum and kidney tissues were collected for study. Biomarkers associated with kidney function, oxidative stress, inflammation and fibrosis were assessed. Our results showed that TCS could cause renal injury as was revealed by increased levels of renal function markers including serum creatinine, urea nitrogen and uric acid, as well as increased oxidative stress, pro-inflammatory cytokines and fibrotic markers in a dose dependent manner, which were more significantly in 100 mg/(kg•day) group. Mass spectrometry-based analysis of metabolites related with lipid metabolism demonstrated the occurrence of lipid accumulation and defective fatty acid oxidation in 100 mg/(kg•day) TCS-exposed mouse kidney. These processes might lead to lipotoxicity and energy depletion, thus resulting in kidney fibrosis and functional decline. Taken together, the present study demonstrated that TCS could induce lipid accumulation and fatty acid metabolism disturbance in mouse kidney, which might contribute to renal function impairment. The present study further widens our insights into the adverse effects of TCS.


Assuntos
Anti-Infecciosos , Transtornos do Metabolismo dos Lipídeos , Triclosan , Animais , Óleo de Milho/metabolismo , Óleo de Milho/farmacologia , Creatinina/metabolismo , Creatinina/farmacologia , Citocinas/metabolismo , Citocinas/farmacologia , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Ácidos Graxos/metabolismo , Fibrose , Rim/metabolismo , Metabolismo dos Lipídeos , Transtornos do Metabolismo dos Lipídeos/induzido quimicamente , Transtornos do Metabolismo dos Lipídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nitrogênio/metabolismo , Triclosan/toxicidade , Ureia , Ácido Úrico/metabolismo , Ácido Úrico/farmacologia
2.
Bull Exp Biol Med ; 173(5): 673-676, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36210427

RESUMO

A common method of modeling urolithiasis is the use of 1 and 0.75% ethylene glycol, or a combination of ethylene glycol with other lithogens, but too rapid progression of the disease and multiple organ toxicity have been reported. We developed a urolithiasis model in Sprague-Dawley rats, in which the animals received a relatively low concentration of ethylene glycol (0.5%), but for a long-term period (6 weeks) followed by animal observation during the 6-week recovery period. In urine samples, signs of the urolithiasis development were observed starting from the sixth week: the presence of ketones, decrease in diuresis and urine pH; in the blood, urea, protein, and hematocrit were elevated. However, no leukocytes were detected in the urine; in the blood, no shifts in differential leukocyte count and no elevation in ALT, creatinine, cholesterol, and triglycerides were observed, which indicates the absence of multiple organ failure while using 1% ethylene glycol. In addition, the animals receiving 0.5% ethylene glycol were followed up to 12 weeks in contrast to animals receiving 1% ethylene glycol (the experiment in this case was stopped during the third week for ethical reasons).


Assuntos
Etilenoglicol , Urolitíase , Animais , Creatinina/metabolismo , Cetonas/metabolismo , Rim/metabolismo , Ratos , Ratos Sprague-Dawley , Triglicerídeos/metabolismo , Ureia/metabolismo , Urolitíase/induzido quimicamente
3.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1490-1495, 2022 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-36208254

RESUMO

OBJECTIVE: To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes in patients with multiple myeloma (MM). METHODS: Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RT-qPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve. RESULTS: The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group (P<0.001), while the expression level of miR-146a between the two groups was not significantly different (P>0.05). The expression level of miR-21 was strongly negatively correlated with serum ß2-microglobulin concentration (r=-0.830), and weakly negatively correlated with serum creatinine, corrected serum calcium, and cystatin C (r=-0.488, -0.282, -0.627). The expression levels of Let-7b and miR-18a were also weakly negatively correlated with the corrected serum calcium, ß2-microglobulin, and cystatin C concentration (r=-0.305, -0.362, -0.461; -0.317, -0.542, -0.434). However, there was no significant correlation between the expression level of miR-146a and routine laboratory parameters in MM patients. The overall survival rate of MM patients with low expression level of miR-21, miR-18a, and Let-7b significantly decreased compared with high expression level group (P<0.05), however, the expression level of miR-146a was not related to the overall survival rate. CONCLUSION: Aberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM, which are associated with a worse overall survival rate.


Assuntos
Exossomos , MicroRNAs , Mieloma Múltiplo , Cálcio/metabolismo , Creatinina/metabolismo , Cistatina C/metabolismo , Exossomos/metabolismo , Humanos , MicroRNAs/metabolismo , Mieloma Múltiplo/metabolismo
4.
Dis Markers ; 2022: 4158692, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36225198

RESUMO

Background: This study investigated the effect and mechanism of rosiglitazone on a rat model with contrast-induced acute kidney injury (CI-AKI). Materials and Methods: The CI-AKI rat model was established from Sprague Dawley rats by furosemide injection (10 ml/kg) to the caudal vein followed by iohexol (11.7 ml/kg). The experimental grouping was randomly allocated into control, model, rosiglitazone, and T0070907 groups. Blood samples were collected from the abdominal aorta. Serum creatinine, urea nitrogen, MDA, and SOD contents were detected by biochemical analysis. TNF-α and IL-10 expression was detected by ELISA. Urine creatinine and urine protein were measured following 24-h urine biochemistry testing. Cell pathology and apoptosis were detected by H&E and TUNEL staining, respectively. PPARγ, NLRP3, eNOS, and caspase-3 mRNA expression were detected by qPCR. Caspase-3 and NLRP3 expression were detected by immunohistochemistry. Results: The CI-AKI rat model was successfully established because the results showed that compared with control, serum creatinine, urea nitrogen, MDA, SOD, TNF-α, and IL-10, urine creatinine and urine protein levels were significantly increased in the model group, indicating AKI, but was significantly decreased with rosiglitazone treatment, indicating recovery from injury, while opposite results were obtained with SOD. Apoptosis rate was significantly increased in the model group and significantly decreased with rosiglitazone treatment. NLRP3 and eNOS increased significantly in the model group and decreased significantly with rosiglitazone treatment, while opposite results were obtained with PPARγ. NLRP3 and caspase-3 protein expression was significantly increased in the model group and significantly decreased with rosiglitazone treatment. Conclusion: Rosiglitazone could alleviate acute renal injury in the CI-AKI rat model by regulating the PPARγ/NLRP3 signaling pathway and should be further investigated as a potential treatment in clinical studies.


Assuntos
Injúria Renal Aguda , Rosiglitazona , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/metabolismo , Animais , Caspase 3/metabolismo , Creatinina/metabolismo , Furosemida/efeitos adversos , Interleucina-10/genética , Interleucina-10/metabolismo , Iohexol/efeitos adversos , Iohexol/metabolismo , Rim/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nitrogênio/metabolismo , Nitrogênio/farmacologia , Nitrogênio/uso terapêutico , PPAR gama/genética , PPAR gama/metabolismo , PPAR gama/farmacologia , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Rosiglitazona/uso terapêutico , Transdução de Sinais , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ureia
5.
Int J Mol Sci ; 23(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36232918

RESUMO

Cyclophosphamide is an anticancer drug with a wide spectrum of clinical uses, but its typical side effects are multiple complications, including nephron toxicity. The possible molecular mechanism of the nephroprotective action of sesamin (SM) against cyclophosphamide (CP) induced renal toxicity was investigated in rats by understanding oxidative stress and inflammatory cytokines. In this study, rats were arbitrarily grouped into the following four groups: a normal control group (CNT); a CP-induced toxicity group; a treatment group with two doses of sesamin SM10 and SM20; a group with sesamin (SM20) alone. A single dose of CP (150 mg/kg body, i.p.) was administered on day 4 of the experiments, while treatment with SM was given orally for seven days from day 1. The group treated with SM showed a significant protective effect against CP-induced renal damage in rats. Treatment with SM significantly increased the antioxidant enzymes (GSH, CAT, and SOD) and reduced malondialdehyde (MDA) levels. Thus, SM significantly overcame the elevated kidney function markers (creatinine, blood urea nitrogen, and uric acid) by attenuating oxidative stress. The SM also significantly reduced the elevated cytokines (IL-1ß and TNFα) and caspase-3 in the treated group. Histopathological studies confirmed the protective effect of sesamin (SM) on CP-induced nephrotoxicity. In conclusion, the current findings support the nephroprotective effect of sesamin against CP-induced renal injury.


Assuntos
Antineoplásicos , Insuficiência Renal , Animais , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Apoptose , Caspase 3/metabolismo , Creatinina/metabolismo , Ciclofosfamida/toxicidade , Citocinas/metabolismo , Dioxóis , Rim/metabolismo , Lignanas , Malondialdeído/metabolismo , Estresse Oxidativo , Ratos , Insuficiência Renal/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ácido Úrico/metabolismo
6.
Int J Mol Sci ; 23(19)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36233032

RESUMO

Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG's effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Fator de Células-Tronco , Albuminas/metabolismo , Animais , Biomarcadores/metabolismo , Creatinina/metabolismo , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Células Endoteliais/metabolismo , Humanos , Mesilato de Imatinib/farmacologia , Glomérulos Renais/metabolismo , Camundongos , Camundongos Endogâmicos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Células-Tronco/metabolismo
7.
Molecules ; 27(19)2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36234730

RESUMO

Cardiac and hepatotoxicities are major concerns in the development of new drugs. Better alternatives to other treatments are being sought to protect these vital organs from the toxicities of these pharmaceuticals. In this regard, a preclinical study is designed to investigate the histopathological effects of a new succinimide derivative (Comp-1) on myocardial and liver tissues, and the biochemical effects on selected cardiac biomarkers, hepatic enzymes, and lipid profiles. For this, an initially lethal/toxic dose was determined, followed by a grouping of selected albino rats into five groups (each group had n = 6). The control group received daily oral saline for 8 days. The 5-FU (5-Fluorouracil) group received oral saline daily for 8 days, added with the administration of a single dose of 5-FU (150 mg/kg I.P.) on day 5 of the study. The atenolol group received oral atenolol (20 mg/kg) for 8 days and 5-FU (150 mg/kg I.P.) on day 5 of the protocol. Similarly, two groups of rats treated with test compound (Comp-1) were administered with 5 mg/kg I.P. and 10 mg/kg I.P. for 8 days, followed by 5-FU (150 mg/kg I.P.) on day 5. Toxicity induced by 5-FU was manifested by increases in the serum creatinine kinase myocardial band (CK-MB), troponin I (cTnI) and lactate dehydrogenase (LDH), lipid profile, and selected liver enzymes, including ALP (alkaline phosphatase), ALT (alanine transaminase), AST (aspartate aminotransferase), BT (bilirubin total), and BD (direct bilirubin). These biomarkers were highly significantly decreased after the administration of the mentioned doses of the test compound (5 mg/kg and 10 mg/kg). Similarly, histological examination revealed cardiac and hepatic tissue toxicity by 5-FU. However, those toxic effects were also significantly recovered/improved after the administration of Comp-1 at the said doses. This derivative showed dose-dependent effects and was most effective at a dose of 10 mg/kg body weight. Binding energy data computed via docking simulations revealed that our compound interacts toward the human beta2-adrenergic G protein-coupled receptor (S = -7.89 kcal/mol) with a slight stronger affinity than the calcium channel T-type (S = -7.07 kcal/mol). In conclusion, the histological and biochemical results showed that the test compound (Comp-1) had prominent cardioprotective, hepatoprotective, and lipolytic effects against 5-FU-induced toxicity in the subjected animal model.


Assuntos
Fosfatase Alcalina , Troponina I , Adrenérgicos/metabolismo , Adrenérgicos/farmacologia , Alanina Transaminase , Fosfatase Alcalina/metabolismo , Animais , Aspartato Aminotransferases , Atenolol , Bilirrubina/metabolismo , Biomarcadores/metabolismo , Canais de Cálcio/metabolismo , Creatinina/metabolismo , Fluoruracila/farmacologia , Humanos , Lactato Desidrogenases/metabolismo , Lipídeos/farmacologia , Fígado , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Succinimidas/metabolismo , Troponina I/metabolismo
8.
Int J Mol Sci ; 23(20)2022 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-36293129

RESUMO

We investigated the nephroprotective effect of D-panthenol in rhabdomyolysis-induced acute kidney injury (AKI). Adult male Wistar rats were injected with 50% glycerol solution to induce rhabdomyolysis. Animals with rhabdomyolysis were injected with D-panthenol (200 mg/kg) for 7 days. On day 8, we examined AKI markers, renal histology, antioxidant capacity, and protein glutathionylation in kidneys to uncover mechanisms of D-panthenol effects. Rhabdomyolysis kidneys were shown to have pathomorphological alterations (mononuclear infiltration, dilatation of tubules, and hyaline casts in Henle's loops and collecting ducts). Activities of skeletal muscle damage markers (creatine kinase and lactate dehydrogenase) increased, myoglobinuria was observed, and creatinine, BUN, and pantetheinase activity in serum and urine rose. Signs of oxidative stress in the kidney tissue of rhabdomyolysis rats, increased levels of lipid peroxidation products, and activities of antioxidant enzymes (SOD, catalase, and glutathione peroxidase) were all alleviated by administration of D-panthenol. Its application improved kidney morphology and decreased AKI markers. Mechanisms of D-panthenol's beneficial effects were associated with an increase in total coenzyme A levels, activity of Krebs cycle enzymes, and attenuation of protein glutathionylation. D-Panthenol protects kidneys from rhabdomyolysis-induced AKI through antioxidant effects, normalization of mitochondrial metabolism, and modulation of glutathione-dependent signaling.


Assuntos
Injúria Renal Aguda , Rabdomiólise , Masculino , Ratos , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Glutationa Peroxidase/metabolismo , Glicerol/metabolismo , Ratos Wistar , Rabdomiólise/complicações , Rabdomiólise/tratamento farmacológico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/induzido quimicamente , Estresse Oxidativo , Rim/metabolismo , Glutationa/metabolismo , Creatina Quinase/metabolismo , Superóxido Dismutase/metabolismo , Coenzima A/metabolismo , Lactato Desidrogenases/metabolismo
9.
Sci Rep ; 12(1): 17593, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36266429

RESUMO

Milk urea concentration is an indicator for dietary nitrogen (N)-supply and urinary N-excretion. Dairy cows with high (HMU) compared to low milk urea (LMU) concentration have greater plasma urea, creatinine and uric acid concentrations, but if the liver metabolism accounts for these differences is unknown. Eighteen HMU and 18 LMU cows were fed a diet with a low (LP) or normal (NP) crude protein concentration. A N balance study was performed and a 13C-urea bolus was administered to measure urea pool size. Liver samples were analyzed by 2D-gel-based proteomics and RT-qPCR. Although HMU cows had a greater urea pool, plasma urea, uric acid, and hippuric acid concentrations, these differences were not associated with altered expressions of genes related to urea cycling or N-metabolism. Instead, HMU cows had higher oxidative stress levels. Conclusively, other factors than hepatic urea metabolism account for milk urea concentrations. Despite higher plasma urea concentrations and argininosuccinate synthase 1 protein expression on the LP diet, urea cycle mRNA expressions were not affected, indicating that its activity is not controlled at transcriptional level. Feeding the LP diet resulted in increased expressions of enzymes catabolizing fatty acids, but the reason remains to be investigated in future studies.


Assuntos
Leite , Ureia , Feminino , Bovinos , Animais , Leite/química , Ureia/metabolismo , Rúmen/metabolismo , Creatinina/metabolismo , Lactação , Ácido Úrico/metabolismo , Ração Animal/análise , Argininossuccinato Sintase/metabolismo , Nitrogênio/metabolismo , Ácidos Graxos/metabolismo , Fígado/metabolismo , RNA Mensageiro/metabolismo
10.
Biomed Pharmacother ; 155: 113758, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36271546

RESUMO

Diabetic nephropathy [DN] is one of the most prevalent microvascular complications of diabetes mellitus [DM] and it is considered a leading cause of kidney failure. In this study calycosin, an isoflavone that constitutes the major constituent in Radix Astragali with numerous pharmacological merits was investigated as reno-protective agent against DN and also the potential underlying mechanisms were investigated. Streptozotocin (STZ) (40 mg/kg) was injected in the peritoneal cavity of male Sprague-Dawely rats to induce DM. For ten weeks, calycosin (5 and 10 mg/kg), and NAC (500 mg/kg) were orally administered and they significantly lowered blood glucose levels, but significantly increased insulin levels. Calycosin improved the deteriorated kidney functions as evidenced in retracted serum creatinine, albuminuria, blood urea nitrogen, and proteinuria levels. Meanwhile, urine creatinine clearance significantly escalated. Furthermore, biomarkers of cell injury; LDH activity, significantly declined and kidney content of NO markedly decreased as well. Inflammation, fibrosis and oxidative stress were manifested by increased serum levels of IL-1ß, renal NF-κBp65, NLRP3, TXNIP and MDA contents with declined levels of IL-10 and TAC and decreased Nrf2 expression. The above-mentioned biomarkers were significantly improved with calycosin treatment which modulated NF-κB/p65/NLRP3/TXNIP signaling, oxidative stress, inflammatory cytokines and fibrotic processes; Thus, implying a reno-protective impact. This was associated with improvement in renal histopathological and immune-histopathological parameters; H&E, Masson Trichrome and Nrf-2. Based on these findings, calycosin can be presumed to be a promising drug for hindering the development of DN through modulation of NF-κB/p65/NLRP3/TXNIP inflammasome signaling pathway.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Insulinas , Isoflavonas , Ratos , Masculino , Animais , Nefropatias Diabéticas/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estreptozocina , Inflamassomos/metabolismo , Creatinina/metabolismo , Interleucina-10/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , NF-kappa B/metabolismo , Glicemia/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Transdução de Sinais , Rim/patologia , Biomarcadores/metabolismo , Insulinas/metabolismo , Insulinas/uso terapêutico
11.
Int J Mol Sci ; 23(19)2022 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-36232596

RESUMO

Vinclozolin is one of the most used fungicides in the control of fungi in fruits, vegetables, and ornamental plants. The effects of its exposure on different organs have been described, but information regarding its relevance to vinclozolin-induced nephrotoxicity is largely missing. This study focuses on the potential mechanism of vinclozolin-induced nephrotoxicity. CD1 male mice were administered vinclozolin (100 mg/kg) by oral gavage for 28 days. Vinclozolin administration decreased body weight over the treatment period and at the end of the experiment, increased the ratio of kidney weight to body weight and increased serum urea nitrogen and creatinine contents. Vinclozolin also induced histopathological alterations, including tubular dilatation and necrosis and impaired the integrity of the renal-tubular architecture and kidney fibrosis. The analyses conducted showed that vinclozolin administration altered the mRNA levels of mitochondrial function-related proteins (SIRT3, SIRT1, PGC-1α, TFAM, NRF1, VDAC-1, and Cyt c) and oxidative stress (increased lipid peroxidation and decreased total antioxidative capacity, catalase, and superoxide dismutase activities, glutathione levels, and glutathione peroxidase activity) in the kidneys. Furthermore, vinclozolin induced toxicity that altered Nrf2 signalling and the related proteins (HO-1 and NQO-1). Vinclozolin administration also affected both the extrinsic and intrinsic apoptotic pathways, upregulating the expression of proapoptotic factors (Bax, Caspase 3, and FasL) and downregulating antiapoptotic factor (Bcl-2) levels. This study suggests that vinclozolin induced nephrotoxicity by disrupting the transcription of mitochondrial function-related factors, the Nrf2 signalling pathway, and the extrinsic and intrinsic apoptotic pathways.


Assuntos
Fungicidas Industriais , Sirtuína 3 , Animais , Antioxidantes/farmacologia , Apoptose , Peso Corporal , Caspase 3/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Fibrose , Fungicidas Industriais/farmacologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Rim/metabolismo , Camundongos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nitrogênio/metabolismo , Oxazóis , Estresse Oxidativo , RNA Mensageiro/metabolismo , Sirtuína 1/metabolismo , Sirtuína 3/metabolismo , Superóxido Dismutase/metabolismo , Ureia/farmacologia , Proteína X Associada a bcl-2/metabolismo
12.
Hum Exp Toxicol ; 41: 9603271221132140, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36198566

RESUMO

Herbacetin (HBN) is a glycosylated flavonoid, which possesses numerous pharmacological properties. Cyclophosphamide (CYC) is a chemotherapeutic drug that adversely affects the kidneys. The present investigation aimed to evaluate the curative potential of HBN against CYC-induced nephrotoxicity. Sprague Dawley rats (n = 48) were randomly divided into four groups: control (0.1% DMSO + food), CYC (150 mg/kg b.wt.), CYC+HBN (150 + 40 mg/kg b.wt.), and HBN (40mg/kg b.wt.). CYC treatment significantly decreased the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GSR) while elevating the concentration of reactive oxygen species (ROS) and malondialdehyde (MDA). Treatment with HBN significantly recovered the activity of CAT, SOD, GPx, and GSR while reducing the concentrations of ROS and MDA. Moreover, an increase in the level of renal functional markers, including Urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), and a decrease in creatinine clearance after CYC administration was recovered to control values by HBN treatment. Furthermore, HBN treatment normalized the increased levels of inflammatory markers such as nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) after CYC administration. Besides, HBN administration increased the expression of anti-apoptotic markers (Bcl-2) while decreasing the apoptotic markers (Bax and Caspase-3). Furthermore, HBN decreased the activities of tricarboxylic acid (TCA) cycle enzymes (ICDH, αKGDH, SDH, and MDH) as well as renal mitochondrial respiratory-chain complexes (I-IV) and repolarized mitochondrial membrane potential (ΔΨm). Additionally, HBN administration significantly protected against renal histological damage induced by CYC. In conclusion, CYC-induced toxicity was effectively ameliorated by the HBN administration. These results indicate that HBN might be considered as a potential protective agent against nephrotoxicity. The observed protection may be due to its antioxidant, anti-inflammatory, and anti-apoptotic potential.


Assuntos
NF-kappa B , Fator de Necrose Tumoral alfa , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Apoptose , Caspase 3/metabolismo , Catalase/metabolismo , Creatinina/metabolismo , Ciclo-Oxigenase 2/metabolismo , Ciclofosfamida/uso terapêutico , Ciclofosfamida/toxicidade , Dimetil Sulfóxido/metabolismo , Dimetil Sulfóxido/farmacologia , Dimetil Sulfóxido/uso terapêutico , Flavonoides/farmacologia , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Rim , Lipocalina-2 , Malondialdeído/metabolismo , Mitocôndrias/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Ácidos Tricarboxílicos/metabolismo , Ácidos Tricarboxílicos/farmacologia , Ácidos Tricarboxílicos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Ureia , Proteína X Associada a bcl-2/metabolismo
13.
Eur J Histochem ; 66(4)2022 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-36190398

RESUMO

Cisplatin (CDDP) has been widely used in cancer therapy, but it has been linked to side effects such as nephrotoxicity. Crocin is a carotenoid found in crocus and gardenia flowers that has been shown to have anti-oxidant properties, inhibit tumor growth, and provide neuroprotection. The purpose of this study was to investigate the protective effect of crocin against CDDP-induced nephrotoxicity in a mouse model. Kunming mice were administered orally with crocin for 7 days at the dose of 6.25 mg/kg and 12.5 mg/kg per body weight daily and were injected with CDDP via intraperitoneal route at the dose of 10 mg/kg per body weight. Using commercial kits, the oxidative stress markers glutathione, malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase were measured in the kidneys of mice. Immunohistochemistry was used to assess the levels of p53, cleaved caspase-3, and phospho-p38 mitogen-activated protein kinase in the kidneys. Crocin significantly reduced CDDP-induced changes in serum creatinine and blood urea nitrogen levels, according to the findings. Crocin reduced malondialdehyde levels and increased glutathione, glutathione peroxidase, catalase, and superoxide dismutase levels in CDDP-induced lipid peroxidation. Crocin also significantly inhibited p38 mitogen-activated protein kinase activation, p53 expression, and caspase-3 cleavage. In conclusion, crocin protects against CDDP-induced oxidative stress and nephrotoxicity by attenuating the activation of p38 mitogen-activated protein kinase and caspase-3 cleavage.


Assuntos
Antineoplásicos , Cisplatino , Animais , Antineoplásicos/toxicidade , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Peso Corporal , Carotenoides/metabolismo , Carotenoides/farmacologia , Carotenoides/uso terapêutico , Caspase 3/metabolismo , Catalase/metabolismo , Cisplatino/metabolismo , Cisplatino/toxicidade , Creatinina/metabolismo , Creatinina/farmacologia , Modelos Animais de Doenças , Glutationa/metabolismo , Glutationa/farmacologia , Glutationa Peroxidase/metabolismo , Glutationa Peroxidase/farmacologia , Rim/metabolismo , Malondialdeído/metabolismo , Malondialdeído/farmacologia , Camundongos , Estresse Oxidativo , Superóxido Dismutase/metabolismo , Superóxido Dismutase/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/farmacologia
14.
Animal ; 16(9): 100627, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36084412

RESUMO

Nutrient deficit during the periparturient period leads to mobilisation of body energy and protein reserves. Research regarding fat reserves and mobilisation is extensive, while, on the contrary, investigation of muscle mobilisation during the periparturient period is limited. The aim of this cohort study was to simultaneously investigate the biological variation of skeletal muscle and subcutaneous fat reserves together with their mobilisation in transition Holstein cows of different herds, using ultrasonography, and to assess potential affecting factors. For this purpose, ultrasound measurements of longissimus dorsi muscle thickness (LDT) and backfat thickness (BFT) from 238 multiparous cows of six dairy farms were obtained at six time points across the transition period (from 21 days pre- to 28 days postpartum). Concentrations of serum creatinine and non-esterified fatty acids were determined in order to confirm the loss of muscle mass and adipose tissue, respectively. Cases of clinical postparturient diseases and subclinical ketosis (scKET) during the first 28 days postcalving were recorded. Cows mobilised on average 32.8% and 37.3% of LDT and BFT reserves, respectively. Large between-cow variation was observed for both the onset and the degree of mobilisation. Time point, initial body condition score and parity were the most important predictors of LDT variation. Cows diagnosed with metritis (MET) had lower LDT postpartum and mobilised more muscle depth compared to cows not diagnosed with MET. Initial BCS, time point, initial BW (estimated by heart girth measurement) and parity were the most important predictors of BFT variation. Cows diagnosed with MET mobilised more backfat between -7d and 7d compared to cows not diagnosed with MET. Cows with scKET mobilised more backfat between 7- and 21 days postpartum compared to healthy ones. Variation of subcutaneous fat and skeletal muscle reserves during the transition period was large and affected by herd and several cow-level factors.


Assuntos
Metabolismo Energético , Lactação , Tecido Adiposo/metabolismo , Animais , Bovinos , Estudos de Coortes , Creatinina/metabolismo , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Lactação/fisiologia , Leite/metabolismo , Músculo Esquelético/metabolismo , Período Pós-Parto , Gravidez
15.
Stem Cell Res Ther ; 13(1): 438, 2022 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056427

RESUMO

BACKGROUND: The therapeutic potential of mesenchymal stem cells (MSCs)-derived conditioned media (CM) can be increased after preconditioning with various chemical agents. The aim of this study is comparative evaluation of effects of N-CM and DFS-CM which are collected from normal (N) and deferoxamine (DFS) preconditioned umbilical cord-derived MSCs on rat diabetic nephropathy (DN) model. METHODS: After incubation of the MSCs in serum-free medium with/without 150 µM DFS for 48 h, the contents of N-CM and DFS-CM were analyzed by enzyme-linked immunosorbent assay. Diabetes (D) was induced by single dose of 55 mg/kg streptozotocin. Therapeutic effects of CMs were evaluated by biochemical, physical, histopathological and immunohistochemical analysis. RESULTS: The concentrations of vascular endothelial growth factor alpha, nerve growth factor and glial-derived neurotrophic factor in DFS-CM increased, while one of brain-derived neurotrophic factor decreased in comparison with N-CM. The creatinine clearance rate increased significantly in both treatment groups, while the improvement in albumin/creatinine ratio and renal mass index values were only significant for D + DFS-CM group. Light and electron microscopic deteriorations and loss of podocytes-specific nephrin and Wilms tumor-1 (WT-1) expressions were significantly restored in both treatment groups. Tubular beclin-1 expression was significantly increased for DN group, but it decreased in both treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cell death increased in the tubules of D group, while it was only significantly decreased for D + DFS-CM group. CONCLUSIONS: DFS-CM can be more effective in the treatment of DN by reducing podocyte damage and tubular apoptotic cell death and regulating autophagic activity with its more concentrated secretome content than N-CM.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Células-Tronco Mesenquimais , Animais , Creatinina/metabolismo , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Desferroxamina , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/metabolismo , Células-Tronco Mesenquimais/metabolismo , Ratos , Cordão Umbilical/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
16.
J Pharm Biomed Anal ; 221: 115028, 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36108463

RESUMO

Tripterygium glycoside tablet (TGT) has been used clinically to alleviate diabetic nephropathy (DN) for decades. However, the mechanism of its anti-DN has not been fully clarified. The aim of this study was to elucidate molecular mechanism of TGT in repairing renal function injury. The results of biochemical parameters and renal histopathology implied that TGT intervention could attenuate creatinine, albumin excretion rate and histological injury of kidney in DN mouse model. Moreover, UHPLC-QTOF-MS/MS-based untargeted metabolomic analysis indicated that 11 metabolites in kidney of mice with DN were restored after TGT treatment, and the most prominent metabolic alteration was triglyceride (TG) metabolism. Mechanistically, TGT effectively improved the function of impaired kidney by promoting TG catabolism via modulation of adipose triglyceride lipase in DN mice. Our findings identified the link between circulating metabolites and DN, suggesting that it might be a possibility to intervene in DN by targeting metabolism.


Assuntos
Glicosídeos Cardíacos , Diabetes Mellitus , Nefropatias Diabéticas , Insuficiência Renal , Albuminas , Animais , Creatinina/metabolismo , Diabetes Mellitus/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Glicosídeos/química , Glicosídeos/farmacologia , Glicosídeos/uso terapêutico , Rim/metabolismo , Lipase , Camundongos , Insuficiência Renal/patologia , Comprimidos/metabolismo , Espectrometria de Massas em Tandem , Triglicerídeos , Tripterygium/química
17.
Br J Hosp Med (Lond) ; 83(8): 1-11, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-36066298

RESUMO

The current diagnosis of acute kidney injury relies on the measurement of serum creatinine levels and urine output. However, both measures are subject to considerable limitations; for example, change in serum creatinine levels ideally requires a knowledge of baseline function that is often not available. Furthermore, creatinine levels are influenced by many factors including diet, drug therapy, muscle mass, gender and ethnicity, which may lead to underestimation of the extent of renal dysfunction. Similarly, urine output lacks both specificity and sensitivity as a marker of acute kidney injury given that oliguria may be an appropriate physiological response to a multitude of stressors and that output may be maintained until significant renal damage has already occurred. Given the well-documented consequences of acute kidney injury and the considerable burden associated with its development, much attention has focused on early identification of patients at high risk to try and improve outcomes. Many studies have focused on the identification of candidate molecules that may enable the early detection of individuals at risk of developing acute kidney injury, including constitutive proteins associated with kidney damage, as well as molecules upregulated in response to injury, non-renal products that may be filtered, reabsorbed or secreted by the kidney, and markers of renal stress. Such biomarkers may also aid stratification for adverse events, such as the need for kidney replacement therapy or progression to chronic kidney disease and end-stage kidney disease. This article discusses some of these novel biomarkers and assesses the role they may have in the understanding, management, diagnosis and prognostication of acute kidney injury.


Assuntos
Injúria Renal Aguda , Injúria Renal Aguda/diagnóstico , Biomarcadores/metabolismo , Creatinina/metabolismo , Humanos , Rim , Terapia de Substituição Renal
18.
Exp Cell Res ; 420(1): 113332, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36084668

RESUMO

Acute renal damage presents a significant danger to kidney health. Previous research has found that acute kidney injury shows high levels of oxidative stress and inflammation caused by sepsis. Although mesenchymal stem cells (MSCs) can repair acute kidney injury. However, involvement of MSCs exosomes generated from adipose tissue and bone marrow in lipopolysaccharide-induced acute kidney damage is not clear. LPS (7.5 mg/kg) intraperitoneal injection was used to produce AKI, and 30 min before the LPS administration, adipose-derived MSCs (ADSCs) exosomes (1 × 105 and 5 × 105) and bone marrow-derived MSCs(BMSCs) exosomes (1 × 105 and 5 × 105) were delivered individually. The function of the rat kidney was explored. Inflammation, oxidative stress, and autophagy levels were further investigated. Both adipose-derived and bone marrow-derived MSCs can enhance renal function and structural damage, such as BUN, Creatinine, and cystatin C levels, as well as tubular damage scores. These findings indicate that both adipose-derived MSCs exosomes and bone marrow-derived MSCs exosomes decrease oxidative stress and inflammation, as well as make a substantial influence on kidney tissue in autophagy levels. Furthermore, compared to bone marrow-derived MSCs exosomes, adipose-derived MSCs exosomes improved kidney function and structure more significantly. We discovered that adipose-derived MSCs exosomes protect against LPS-induced AKI by inhibiting oxidative stress and inflammation.


Assuntos
Injúria Renal Aguda , Exossomos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Injúria Renal Aguda/terapia , Tecido Adiposo , Animais , Creatinina/efeitos adversos , Creatinina/metabolismo , Cistatina C/efeitos adversos , Cistatina C/metabolismo , Exossomos/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/efeitos adversos , Estresse Oxidativo , Ratos , Células-Tronco
19.
Animal ; 16(10): 100632, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36155278

RESUMO

Protein supplements are expensive and not easily accessible under small-scale livestock production systems in Ethiopia and other developing countries, which necessitates investigating the alternative protein sources for cost-effective livestock production. Pigeon pea (Cajanus cajan L. Millsp) leaves (PPLs) are rich in protein and are well-suited for feeding small ruminants; however, the effect of inclusion of PPL in the concentrate mixture (CM) on the performance of dairy cows was not well documented. This experiment was conducted to evaluate the effect of supplementation of PPL and CM to native pasture hay-based rations on feed intake, milk yield and composition, and blood metabolites of crossbred dairy cows (Holstein × Zebu). A 4 × 4 Latin square design with three replications, balanced for carryover effects, was used for this study. The treatments included native pasture hay provided ad libitum as a basal diet, supplemented with a CM alone (T1), the inclusion of 10% of PPL in the CM (T2), 20% PPL in the CM (T3), or 30% PPL in the CM (T4). Supplements were isocaloric and isonitrogenous. Total DM intake (hay + supplement intake) was similar (P > 0.05) among treatments. Hay intake was greater (P = 0.05) for T1 and T2 than for T4, while supplement intake was the least for T1 (P < 0.05). The treatment groups T2, T3, and T4, where PPL was included, had similar (P > 0.05) supplement intake. Feed intake, milk yield and composition, feed conversion efficiency, body condition score, serum total protein, albumin, globulin, glucose, triglyceride, urea N, creatinine, and cholesterol were similar (P > 0.05) among treatments. The inclusion of up to 30% of PPL in the CM resulted in a comparable performance of crossbred dairy cows as supplementation with CM under the conditions of the current experiment. Therefore, further study is required to evaluate the effect of the inclusion of a higher level of PPL in the concentrate mixture on the performance of lactating crossbred dairy cows.


Assuntos
Cajanus , Leite , Albuminas/metabolismo , Albuminas/farmacologia , Ração Animal/análise , Animais , Bovinos , Creatinina/metabolismo , Creatinina/farmacologia , Dieta/veterinária , Suplementos Nutricionais , Ingestão de Alimentos , Feminino , Glucose/metabolismo , Lactação , Leite/metabolismo , Triglicerídeos/metabolismo , Ureia/metabolismo
20.
Biomed Res Int ; 2022: 4547312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36132073

RESUMO

Introduction: Diabetic nephropathy is one of the leading causes of end-stage renal disease worldwide. Uncontrolled hyperglycemia and subsequent production of glycation end-products activate the paths which lead to diabetic nephropathy. The aim of this study was to assess the effects of L-lysine on antioxidant capacity, biochemical factors, kidney function, HSP70 level, and the expression of the TGFß, VEGF, and RAGE genes in rats with streptozocin-induced diabetes mellitus. Methods: Thirty-two male Wistar rats were randomly allocated to four eight-rat groups, namely, a healthy group, a diabetic group treated with vehicle (DM + vehicle), a diabetic group treated with L-lysine (DM + Lys), and a healthy group treated with L-lysine (healthy + Lys). Rats in the DM + Lys and the healthy + Lys groups were treated with L-lysine 0.15%. The levels of fasting blood glucose, insulin, HbA1C, advanced glycation end-products (AGEs), lipid profile, serum creatinine, blood urea nitrogen, glomerular filtration rate, urine microalbumin, oxidative stress parameters, kidney histology and morphology, and TGFß, VEGF, and RAGE gene expressions were assessed. Findings. An eight-week treatment with L-lysine significantly reduced the levels of fasting blood glucose, AGEs, kidney function parameters, oxidative stress parameters, lipid profile, and the TGFß, VEGF, and RAGE gene expression and significantly increased the levels of serum insulin and tissue HSP70. Conclusion: Treatment with L-lysine seems to slow down the progression of diabetic nephropathy.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Glicemia/metabolismo , Creatinina/metabolismo , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Insulina/metabolismo , Rim/patologia , Lipídeos , Lisina/metabolismo , Lisina/farmacologia , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Estreptozocina/farmacologia , Fator de Crescimento Transformador beta/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
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