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1.
Gene ; 820: 146293, 2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35143943

RESUMO

Cisplatin (CP) is an anticancer medication that is commonly used to treat solid tumors. Its use is, however, dose-restricted due to nephrotoxicity. We planned to compare the nephroprotective effects of three major compounds, including melatonin (MN), Ozone, or vitamin E, against the CP-induced renal damage in rats. CP was given once intraperitoneally (10 mg/kg,) eliciting acute kidney injury as assured by several adverse histological changes; glomerulopathy, tubulopathy, and vasculopathy, an inflammatory response including elevated TNF-α, IL-6, and IL-1ß. Furthermore, biochemical alterations including, elevated plasma levels of urea, uric acid, creatinine, phosphorous, decreased plasma calcium levels, and gene expression abnormalities; upregulation of N-acetyl-ß-d-glucosaminidase (NAG) and Transforming growth factor-ß1 (TGF-ß1), downregulation of CAT and SOD. Concurrent supplementation with either MN (10 mg/kg per os) or Ozone (1.1 mg/kg ip) and Vit E given by oral gavage (1 g/kg) for five consecutive days prior to CP injection and five days afterward displayed variable significant nephroprotective effects by mitigating the pro-inflammatory secretion, augmenting antioxidant competence, and modulating the gene expression in the renal tissue. The obtained biochemical, histological, and gene expression data suggested that MN had foremost rescue effects followed by Ozone then Vit E. MN's ameliorative effect was augmented in many indices including TNF-α, IL-6 , IL1-ß, uric acid, creatinine, sNGAL and GGT, more than observed in Ozone, and Vit E therapy. A combination of these medications is expected to be more useful in relieving the damaging renal effects of CP given to cancer patients, pending further toxicological and pharmacological research.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Fator 15 de Diferenciação de Crescimento/metabolismo , Melatonina/farmacologia , Ozônio/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Vitamina E/farmacologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/metabolismo , Animais , Antineoplásicos/farmacologia , Antioxidantes/metabolismo , Cisplatino/farmacologia , Cisplatino/toxicidade , Creatinina/sangue , Modelos Animais de Doenças , Expressão Gênica , Fator 15 de Diferenciação de Crescimento/efeitos dos fármacos , Masculino , Melatonina/metabolismo , Neoplasias/tratamento farmacológico , Ozônio/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/efeitos dos fármacos , Ureia/sangue , Vitamina E/metabolismo
2.
Pathol Res Pract ; 230: 153756, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35032832

RESUMO

BACKGROUND: Mesenchymal stromal cells (MSC) have demonstrated ability to improve diabetic nephropathy (DN) in experimental models, as well as by improving kidney endogenous progenitor cells proliferation and differentiation. Many studies have demonstrated the effect of hypoxia on MSC improving their functionality but the potential enhancement of the nephroprotective properties of MSC cultured under low oxygen concentration has been explored in few studies, none of them in the context of DN. On the other hand, diabetes is associated with abnormalities in MSCs functionality. These findings related to the hypoxia preconditioning ability to enhance adipose-tissue derived-MSC (ASC) performance have led us to wonder if hypoxia could increase the known beneficial effect of normal ASC in DN and if it could correct the expected inability of diabetic rat-derived ASC to exert this effect in vivo. To answer these questions, in the present study we have used ASC from healthy and diabetic-induced rats, cultured under standard conditions or hypoxia preconditioned, in a DN rat model induced by streptozotocin (STZ). METHODS: Diabetes was induced in Wistar-rats by 60 mg/kg streptozotocin (STZ) intraperitoneal injection. Fifteen days thereafter, five diabetic-induced rats and five healthy, previously injected with saline, were sacrificed and used as ASC donors . Both healthy and diabetic rat-derived ASC (cASC and dASC, respectively) were cultured under standard conditions (21%O2)(N) or were subjected to a 48 h conditioning period in hypoxia (3%O2)(H). Thus, four types of cells were generated depending on their origin (healthy or diabetic-induced rats) and the culture conditions(N or H):cASC-N, cASC-H, dASC-N and dASC-H. DN experimental study were carried out fifteen days after STZ induction of diabetes in fifty-two healthy rats. DN-induced-animals were randomly assigned to be injected with 200 µL saline as placebo or with 3 × 106 cASC-N, cASC-H, dASC-N or dASC-H, according to the study group. Serum glucose, urea and creatinine, and urine albumin levels were measured at 2-weeks intervals until day+ 45 after ND-induction.Animals were sacrificed and kidneys extracted for histopathological and transmission electron microcopy analysis RESULTS: None of the four study groups that received cell treatment showed significant changes in serum glucose, urea and creatinine levels, urine albumin concentration and body weight compared to placebo ND-induced group. Interestingly, only the group that received cASC-H showed a reduction in glucose and creatinine levels although it did not reach statistical significance.All DN-induced groups treated with ASC reduced significantly renal lesions such as mesangial expansion, mesangiolysis, microaneurysms and acute tubular necrosis compared to ND-induced placebo group (p ≤ 0.05). Renal injuries such as clear tubular cell changes, thickening of tubular basement membrane, tubular cysts and interstitial fibrosis significantly showed reduction in ND-induced rats treated with cASC-H regarding to their received cASCN (p ≤ 0.05). Non statistical differences were observed in the improvement capacity of cASC and dASC culture under standard condition.However, hypoxia preconditioning reduces the presence of tubular cysts (p ≤ 0.01). CONCLUSIONS: Hypoxia preconditioning enhances the ability of healthy rat-derived ASC to improve kidney injury in a rat model of DN. Moreover, diabetic-derived ASC exhibits a similar ability to healthy ASC which is clearly more than expected, but it is not significantly modified by hypoxia preconditioning.


Assuntos
Diabetes Mellitus Experimental/cirurgia , Nefropatias Diabéticas/cirurgia , Rim/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/metabolismo , Tecido Adiposo/citologia , Albuminúria/induzido quimicamente , Albuminúria/cirurgia , Albuminúria/urina , Animais , Glicemia/metabolismo , Hipóxia Celular , Proliferação de Células , Células Cultivadas , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/induzido quimicamente , Nefropatias Diabéticas/patologia , Fibrose , Rim/metabolismo , Masculino , Ratos Wistar , Estreptozocina , Ureia/sangue
3.
Science ; 375(6579): 460-463, 2022 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-35084962

RESUMO

Hibernation is a mammalian strategy that uses metabolic plasticity to reduce energy demands and enable long-term fasting. Fasting mitigates winter food scarcity but eliminates dietary nitrogen, jeopardizing body protein balance. Here, we reveal gut microbiome-mediated urea nitrogen recycling in hibernating thirteen-lined ground squirrels (Ictidomys tridecemlineatus). Ureolytic gut microbes incorporate urea nitrogen into metabolites that are absorbed by the host, with the nitrogen reincorporated into the squirrel's protein pool. Urea nitrogen recycling is greatest after prolonged fasting in late winter, when urea transporter abundance in gut tissue and urease gene abundance in the microbiome are highest. These results reveal a functional role for the gut microbiome during hibernation and suggest mechanisms by which urea nitrogen recycling may contribute to protein balance in other monogastric animals.


Assuntos
Bactérias/metabolismo , Microbioma Gastrointestinal/fisiologia , Hibernação , Nitrogênio/metabolismo , Sciuridae/metabolismo , Sciuridae/microbiologia , Ureia/metabolismo , Animais , Ceco/metabolismo , Ceco/microbiologia , Jejum , Feminino , Fígado/metabolismo , Masculino , Biossíntese de Proteínas , Estações do Ano , Simbiose , Ureia/sangue , Urease/genética , Urease/metabolismo
4.
J Obstet Gynaecol ; 42(1): 55-60, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33938370

RESUMO

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.


Assuntos
Cromogranina A/sangue , Fragmentos de Peptídeos/sangue , Pré-Eclâmpsia/sangue , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Gravidez , Ureia/sangue , Ácido Úrico/sangue
5.
Eur Arch Psychiatry Clin Neurosci ; 272(1): 41-52, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33710424

RESUMO

The objective is to investigate coronavirus disease 2019 (COVID-19)-associated neurological and psychiatric effects and explore possible pathogenic mechanisms. This study included 77 patients with laboratory-confirmed COVID-19 in Wuhan, China. Neurological manifestations were evaluated by well-trained neurologists, psychologists, psychiatric presentations and biochemical changes were evaluated using the Generalized Anxiety Disorder 7-item scale, Patient Health Questionnaire-9, Brief Psychiatric Rating Scale, and electronic medical records. Eighteen (23.4%) patients presented with neurological symptoms. Patients with neurological presentations had higher urea nitrogen, cystatin C, and high-sensitivity C-reactive protein levels and lower basophil counts. Among them, patients with muscle involvement had higher urea nitrogen and cystatin C levels but lower basophil counts. In addition, patients with psychiatric presentations were older and had higher interleukin (IL)-6 and IL-10 levels and higher alkaline phosphatase, R-glutamate transferase, and urea nitrogen levels. Moreover, patients with anxiety had higher IL-6 and IL-10 levels than those without, and patients with moderate depression had higher CD8 + T cell counts and lower CD4 + /CD8 + ratios than other patients. This study indicates that the central nervous system may be influenced in patients with COVID-19, and the pathological mechanisms may be related to direct virus invasion of the central nervous system, infection-mediated overreaction of the immune system, and aberrant serum pro-inflammatory factors. In addition, basophils and cystatin C may also play important roles during these pathological processes. Our findings suggest that neurological and psychiatric presentations should be evaluated and managed in patients with COVID-19. Further studies are needed to investigate the underlying mechanisms.


Assuntos
COVID-19 , Transtornos Mentais , Doenças do Sistema Nervoso , Proteína C-Reativa/análise , COVID-19/fisiopatologia , COVID-19/psicologia , China/epidemiologia , Cistatina C/sangue , Humanos , Interleucina-10/sangue , Transtornos Mentais/sangue , Transtornos Mentais/epidemiologia , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/epidemiologia , Ureia/sangue
6.
Int Clin Psychopharmacol ; 37(1): 25-28, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34686643

RESUMO

Lithium, a mood stabilizer used in the treatment of bipolar disorder is known for its anti-inflammatory properties with the discussion of its potential use in COVID-19 infection. The SARS-CoV-2 virus causing COVID-19 infection is known to enter the target cells through angiotensin converting enzyme-2 receptors present in abundance in the lung and renal tissue. Recent research supports the evidence for direct renal injury by viral proteins. Here we report two patients with bipolar disorder presenting with lithium toxicity in the presence of COVID-19 infection. Two patients with bipolar disorder, maintaining remission on lithium prophylaxis, presented to the psychiatric emergency with recent-onset fever and altered sensorium. Both the patient's investigations revealed lithium toxicity, elevated serum creatinine, urea and inflammatory markers. Hypernatremia, hyperkalaemia, and hyperchloremia were seen in one patient. Lithium and other psychotropic medications were stopped immediately, and COVID-19 treatment was initiated. Patient with clinical signs of lithium toxicity, hypernatremia, hyperkalaemia, and hyperchloremia developed ventricular tachycardia. He survived and regained consciousness after 2 weeks of aggressive conservative management. However, another patient died of acute respiratory failure on day 3. Possible direct infection of the kidney by SARS-CoV-2 viral proteins can manifest with acute kidney injury and lithium toxicity among patients on long-term lithium therapy. Health professionals treating COVID-19 infection among individuals on lithium therapy should be aware of the possibility of lithium toxicity in the background of renal injury.


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Antimaníacos/efeitos adversos , COVID-19/complicações , Compostos de Lítio/efeitos adversos , Antimaníacos/uso terapêutico , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Creatinina/sangue , Evolução Fatal , Humanos , Hiperpotassemia/induzido quimicamente , Hipernatremia/induzido quimicamente , Compostos de Lítio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Insuficiência Respiratória/induzido quimicamente , Taquicardia Ventricular/induzido quimicamente , Ureia/sangue
7.
Drug Des Devel Ther ; 15: 4865-4873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876808

RESUMO

BACKGROUND: A new UPLC-MS/MS technique for the determination of ripretinib in beagle dog plasma was developed, and the pharmacokinetic effects of voriconazole and itraconazole on ripretinib in beagle dogs were studied. METHODS: After extraction with ethyl acetate under alkaline conditions, ripretinib was detected using avapritinib as the internal standard (IS). The mobile phases were 0.1% formic acid-acetonitrile. The scanning method was multi-reaction monitoring using ESI+ source, and the ion pairs for ripretinib and IS were m/z 509.93→416.85 and 499.1→482.09, respectively. This animal experiment adopted a three period self-control experimental design. In the first period, ripretinib was orally administered to six beagle dogs at a dose of 5 mg/kg. In the second period, the same six beagle dogs were orally given itraconazole at a dose of 7 mg/kg, after 30 min, ripretinib was orally given. In the third period, voriconazole at a dose of 7 mg/kg was given orally, and then ripretinib was orally given. At different time points, the blood samples were collected. The concentration of ripretinib was detected, and the pharmacokinetic parameters of ripretinib were calculated. RESULTS: Ripretinib had a good linear relationship in the range of 1-1000 ng/mL. The precision, accuracy, recovery, matrix effect and stability met the requirements of the guiding principles. After erdafitinib combined with itraconazole, the Cmax and AUC0→t of ripretinib increased by 38.35% and 36.36%, respectively, and the t1/2 was prolonged to 7.53 h. After ripretinib combined with voriconazole, the Cmax and AUC0→t of ripretinib increased by 37.44% and 25.52%, respectively, and the t1/2 was prolonged to 7.33 h. CONCLUSION: A new and reliable UPLC-MS/MS technique was fully optimized and developed to detect the concentration of ripretinib in beagle dog plasma. Itraconazole and voriconazole could inhibit the metabolism of ripretinib in beagle dogs and increase the plasma exposure of ripretinib.


Assuntos
Itraconazol/farmacocinética , Naftiridinas/farmacocinética , Ureia/análogos & derivados , Voriconazol/farmacocinética , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Cães , Feminino , Itraconazol/sangue , Itraconazol/química , Masculino , Naftiridinas/sangue , Naftiridinas/química , Espectrometria de Massas em Tandem , Ureia/sangue , Ureia/química , Ureia/farmacocinética , Voriconazol/sangue , Voriconazol/química
8.
ScientificWorldJournal ; 2021: 1393372, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34887703

RESUMO

Aging is a biological process that impacts multiple organs. Unfortunately, kidney aging affects the quality of life with high mortality rate. So, searching for innovative nonpharmacological modality improving age-associated kidney deterioration is important. This study aimed to throw more light on the beneficial effect of treadmill exercise on the aged kidney. Thirty male albino rats were divided into three groups: young (3-4 months old), sedentary aged (23-24 months old), and exercised aged (23-24 months old, practiced moderate-intensity treadmill exercise 5 days/week for 8 weeks). The results showed marked structural alterations in the aged kidney with concomitant impairment of kidney functions and increase in arterial blood pressure with no significant difference in kidney weight. Also, it revealed that treadmill exercise alleviated theses effects in exercised aged group with reduction of urea and cystatin C. Exercise training significantly decreased glomerulosclerosis index, tubular injury score, and % area of collagen deposition. Treadmill exercise exerted its beneficial role via a significant reduction of C-reactive protein and malondialdehyde and increase in total antioxidant capacity. In addition, exercise training significantly decreased desmin immunoreaction and increased aquaporin-3, vascular endothelial growth factor, and beclin-1 in the aged kidney. This study clarified that treadmill exercise exerted its effects via antioxidant and anti-inflammatory mechanisms, podocyte protection, improving aquaporin-3 and vascular endothelial growth factor expression, and inducing autophagy in the aged kidney. This work provided a new insight into the promising role of aerobic exercise to ameliorate age-associated kidney damage.


Assuntos
Envelhecimento/fisiologia , Rim/anatomia & histologia , Rim/fisiologia , Condicionamento Físico Animal , Animais , Antioxidantes/metabolismo , Aquaporina 3/metabolismo , Proteína Beclina-1/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Peso Corporal , Proteína C-Reativa/metabolismo , Cistatina C/sangue , Desmina/metabolismo , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Ureia/sangue , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Medicine (Baltimore) ; 100(44): e27636, 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34871232

RESUMO

ABSTRACT: This study was to identify risk factors affecting postembolization fever (PEF) of CalliSpheres drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of primary hepatocellular carcinoma (HCC).One hundred eighty-eight consecutive patients with HCC who underwent DEB-TACE with fever between June 2017 and May 2019 were included in this retrospective study. The patients were divided into 4 groups based on the severity of posttransarterial chemoembolization (TACE) fever according to the degrees of body temperature. Univariate analysis and multivariate logistics regression were performed to identify potential risk factors for post-TACE fever.In the stepwise multiple regression analysis, pre-TACE blood urea, small particle size and Cental liqefction (P < .05) were independent risk factors of severe post-TACE fever (P < .05, respectively). Portal vein thrombosis (P < .01), Child-Pugh stage (P < .01), and cycles of DEB-TACE (P < .05) were independent risk factors for clinical death, PEF was not associated with clinical death (P = .754) and 6-month survival (P = .524) in the univariate analysis. Moreover, multivariate Cox regression was performed, and Child-Pugh stage (B vs A) (P = .040) and portal vein thrombosis (yes vs no) (P = .033) were independent factors predicting unfavorable overall survival in HCC patients.Pre-TACE blood urea, small particle size, and Cental liqefction were significantly correlated with the occurrence fever after DEB-TACE. Therefore, these factors should be taken into full consideration for the relief of fever. However, PEF after D-TACE was not associated with clinical death and 6-month survival rate.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/efeitos adversos , Febre/etiologia , Neoplasias Hepáticas/terapia , Ureia/sangue , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Quimioembolização Terapêutica/métodos , China/epidemiologia , Feminino , Febre/epidemiologia , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Trombose Venosa
10.
Eur Rev Med Pharmacol Sci ; 25(22): 7089-7092, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34859873

RESUMO

OBJECTIVE: Febrile convulsion (FC) is one of the most common neurological findings in children. This study was aimed to investigate the difference in laboratory parameters between Febrile Seizure and control groups. PATIENTS AND METHODS: In this study, 169 children admitted to the pediatric emergency department with their first episode of FS and 189 control groups were retrospectively analyzed. The demographic characteristics and laboratory parameters of children were obtained from their files. RESULTS: Upper respiratory tract infection (URTI) was determined the most common disease (81.6%) in the FC group followed by acute gastroenteritis (AGE) (15.4%) and urinary tract infection (UTI) (3%), respectively. Similarly, URTI was detected as the most common disease (81.8%) in control groups. It was determined that there was no statistically significant difference between the two groups in terms of diseases. The leukocyte and neutrophil counts of the children with FC were significantly higher but the mean corpuscular volume of lenfosit and lenfosit/neutrophil ratio was significantly lower than the control groups (p= 0.009, <0.001, 0.001, <0.001, <0.001, respectively). Children with FC had significantly higher blood glucose, urea, creatinine, creatine kinase, alkaline phosphatase and albumin levels compared with the control groups (p<0.001, in all parameters). On the other hand, the potassium, sodium and chlorine levels of the Children with FCs were significantly lower than control groups (p=0.017, <0.001, p <0.001, respectively). CONCLUSIONS: To conclude, febrile patients with high leukocyte counts, high neutrophil counts, and several biochemical parameters should be carefully monitored for FCs due to the increasing seizure risk.


Assuntos
Febre/sangue , Convulsões Febris/sangue , Fosfatase Alcalina/sangue , Glicemia/análise , Criança , Pré-Escolar , Cloro/sangue , Creatina/sangue , Creatina Quinase/sangue , Feminino , Humanos , Lactente , Contagem de Leucócitos , Masculino , Fatores de Risco , Albumina Sérica/análise , Sódio/sangue , Ureia/sangue
11.
Sci Rep ; 11(1): 22414, 2021 11 17.
Artigo em Inglês | MEDLINE | ID: mdl-34789813

RESUMO

In pasture-based systems, there are nutritional and climatic challenges exacerbated across lactation; thus, dairy cows require an enhanced adaptive capacity compared with cows in confined systems. We aimed to evaluate the effect of lactation stage (21 vs. 180 days in milk, DIM) and Holstein genetic strain (North American Holstein, NAH, n = 8; New Zealand Holstein, NZH, n = 8) on metabolic adaptations of grazing dairy cows through plasma metabolomic profiling and its association with classical metabolites. Although 67 metabolites were affected (FDR < 0.05) by DIM, no metabolite was observed to differ between genetic strains while only alanine was affected (FDR = 0.02) by the interaction between genetic strain and DIM. However, complementary tools for time-series analysis (ASCA analysis, MEBA ranking) indicated that alanine and the branched-chain amino acids (BCAA) differed between genetic strains in a lactation-stage dependent manner. Indeed, NZH cows had lower (P-Tukey < 0.05) plasma concentrations of leucine, isoleucine and valine than NAH cows at 21 DIM, probably signaling for greater insulin sensitivity. Metabolic pathway analysis also revealed that, independently of genetic strains, AA metabolism might be structurally involved in homeorhetic changes as 40% (19/46) of metabolic pathways differentially expressed (FDR < 0.05) between 21 and 180 DIM belonged to AA metabolism.


Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Bovinos/sangue , Bovinos/genética , Lactação/sangue , Leite/química , Ácido 3-Hidroxibutírico/sangue , Alanina/sangue , Animais , Glicemia/metabolismo , Dieta/veterinária , Ácidos Graxos não Esterificados/sangue , Feminino , Insulina/sangue , Metaboloma/genética , Metabolômica/métodos , Ureia/sangue
12.
PLoS One ; 16(10): e0258145, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34614017

RESUMO

Recent studies suggest that dysbiosis in chronic kidney disease (CKD) increases gut-derived uremic toxins (GDUT) generation, leads to systemic inflammation, reactive oxygen species generation, and poor prognosis. This study aimed to investigate the effect of oligofructose-enriched inulin supplementation on GDUT levels, inflammatory and antioxidant parameters, renal damage, and intestinal barrier function in adenine-induced CKD rats. Male Sprague-Dawley rats were divided into control group (CTL, n = 12) fed with standard diet; and CKD group (n = 16) given adenine (200 mg/kg/day) by oral gavage for 3-weeks to induce CKD. At the 4th week, CKD rats were subdivided into prebiotic supplementation (5g/kg/day) for four consecutive weeks (CKD-Pre, n = 8). Also, the control group was subdivided into two subgroups; prebiotic supplemented (CTL-Pre, n = 6) and non-supplemented group (CTL, n = 6). Results showed that prebiotic oligofructose-enriched inulin supplementation did not significantly reduce serum indoxyl sulfate (IS) but did significantly reduce serum p-Cresyl sulfate (PCS) (p = 0.002) in CKD rats. Prebiotic supplementation also reduced serum urea (p = 0.008) and interleukin (IL)-6 levels (p = 0.001), ameliorated renal injury, and enhanced antioxidant enzyme activity of glutathione peroxidase (GPx) (p = 0.002) and superoxide dismutase (SOD) (p = 0.001) in renal tissues of CKD rats. No significant changes were observed in colonic epithelial tight junction proteins claudin-1 and occludin in the CKD-Pre group. In adenine-induced CKD rats, oligofructose-enriched inulin supplementation resulted in a reduction in serum urea and PCS levels, enhancement of the antioxidant activity in the renal tissues, and retardation of the disease progression.


Assuntos
Inflamação/tratamento farmacológico , Inulina/farmacologia , Oligossacarídeos/farmacologia , Prebióticos , Insuficiência Renal Crônica/tratamento farmacológico , Adenina/toxicidade , Animais , Nitrogênio da Ureia Sanguínea , Cresóis/sangue , Modelos Animais de Doenças , Disbiose/sangue , Disbiose/microbiologia , Humanos , Indicã/sangue , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/patologia , Interleucina-6/sangue , Ratos , Espécies Reativas de Oxigênio/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/induzido quimicamente , Ésteres do Ácido Sulfúrico/sangue , Ureia/sangue
13.
Pak J Pharm Sci ; 34(3): 869-874, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34602408

RESUMO

Salicylic acid, a phenolic compound, found in plants, possesses free radical scavenging and iron chelation properties. The present study is designed to study the antioxidant effect of salicylic acid in gentamicin induced nephrotoxicity in rabbits. For this purpose twenty four male albino rabbits were divided into 4 groups (n=6); control group, healthy untreated rabbits, gentamicin group, received only gentamicin (80mg/kg), gentamicin + salicylic acid group, received gentamicin (80mg/kg) + salicylic acid (80mg/kg) and salicylic acid group, received only salicylic acid (80mg/kg) via intra peritoneal route for 21 consecutive days. Biochemical evaluation was carried out by assessment of body weights and by estimating renal function tests (plasma urea, plasma creatinine and plasma uric acid), tissue antioxidant enzymes (catalase, SOD) and MDA level. Gentamicin induction resulted in decreased body weights, increased plasma urea, plasma creatinine, plasma uric acid, tissue MDA level and decreased tissue SOD and tissue catalase activity in gentamicin treated group which was restored by supplementation with salicylic acid in gentamicin + salicylic acid group. Our data suggests that supplementation of salicylic acid can be useful in reducing gentamicin induced nephrotoxicity in rabbits.


Assuntos
Injúria Renal Aguda/induzido quimicamente , Antibacterianos/toxicidade , Antioxidantes/farmacologia , Gentamicinas/toxicidade , Rim/efeitos dos fármacos , Ácido Salicílico/farmacologia , Injúria Renal Aguda/metabolismo , Animais , Peso Corporal/efeitos dos fármacos , Catalase/efeitos dos fármacos , Catalase/metabolismo , Creatinina/sangue , Rim/metabolismo , Malondialdeído/metabolismo , Coelhos , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Ureia/sangue , Ácido Úrico/sangue
14.
Biomarkers ; 26(8): 718-725, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34612093

RESUMO

AIMS: Oxido-inflammatory stress has been implicated as the main targets in alleviating diabetic complications induced by hyperglycaemia. Dryopteris dilatata: a bioactive plant serves great medicinal benefits in ethnopharmacology to ameliorate pathological conditions. This study investigated the protective effects of ethanol extract of Dryopteris dilatata (EEDD) in alloxan-induced diabetic rats through mechanism involving inhibition of oxidative stress and liver and kidney inflammatory markers. METHODOLOGY: Male Wistar rats were made diabetic via alloxan monohydrate (100 mg/kg) administration intraperitoneally. Diabetic rats were post-treated with EEDD (800 mg/kg) and Metformin (50 mg/kg) orally for two weeks. Fasting blood sugar (FBS), body and organ weight change, markers of oxidative stress, liver and kidney inflammation were evaluated. RESULTS: Our results revealed that EEDD significantly reduced alloxan-induced hyperglycaemia in the diabetic rats after 5, 10 and 15 days of treatment. Markers of oxidative injury were also significantly ameliorated in the pancreas, liver and kidney of the diabetic rats following treatment with EEDD. However, liver and kidney injury markers were significantly attenuated with marked decreased organ weight in the diabetic rats after treatment with EEDD. CONCLUSION: Here in, we found that Dryopteris dilatata could be used as nutraceuticals in the prevention and treatment of diabetes and its related complications through positively modulating oxidative stress and liver and kidney inflammatory markers.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/prevenção & controle , Dryopteris/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alanina Transaminase/metabolismo , Fosfatase Alcalina , Aloxano , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Aspartato Aminotransferases/metabolismo , Glicemia/metabolismo , Catalase/metabolismo , Creatinina/sangue , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Etanol/química , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Fitoterapia/métodos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Superóxido Dismutase/metabolismo , Ureia/sangue
15.
Aging (Albany NY) ; 13(17): 20915-20934, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34492634

RESUMO

Due to global aging, frailty and sarcopenia are increasing. Sarcopenia is defined as loss of volume and strength of skeletal muscle in elderlies, while frailty involves multiple domains of aging-related dysfunction, impaired cognition, hypomobility, and decreased social activity. However, little is known about the metabolic basis of sarcopenia, either shared with or discrete from frailty. Here we analyzed comprehensive metabolomic data of human blood in relation to sarcopenia, previously collected from 19 elderly participants in our frailty study. Among 131 metabolites, we identified 22 sarcopenia markers, distinct from 15 frailty markers, mainly including antioxidants, although sarcopenia overlaps clinically with physical frailty. Notably, 21 metabolites that decline in sarcopenia or low SMI are uremic compounds that increase in kidney dysfunction. These comprise TCA cycle, urea cycle, nitrogen, and methylated metabolites. Sarcopenia markers imply a close link between muscle and kidney function, while frailty markers define a state vulnerable to oxidative stress.


Assuntos
Envelhecimento , Antioxidantes/metabolismo , Idoso Fragilizado , Fragilidade/metabolismo , Rim/metabolismo , Músculo Esquelético/metabolismo , Sarcopenia/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Ciclo do Ácido Cítrico , Feminino , Humanos , Masculino , Força Muscular , Músculo Esquelético/fisiopatologia , Nitrogênio/sangue , Ureia/sangue , Uremia/metabolismo
16.
Nutrients ; 13(9)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34578900

RESUMO

Protein intake in early life influences metabolism, weight gain, and later obesity risk. As such, a better understanding of the effects of protein intake on the postprandial metabolism and its dynamics over time may elucidate underlying mechanisms. In a randomized crossover study, we observed fasted adults who consumed two isocaloric toddler milk formulas concentrated as meals of 480 kcal with 67 g of carbohydrates 30 g (HP) or 7 g (LP) protein, and 10 g or 20 g fat, respectively. Anthropometry and body plethysmography were assessed, and blood samples collected at baseline and over five hours. Time-specific concentrations, areas under concentration curves (AUC), and maximum values of metabolites were compared by paired t-tests to examine the effects of protein content of toddler milks on postprandial plasma concentrations of insulin, glucose, branched-chain amino acids (BCAA), urea and triglycerides. Twenty-seven men and women aged 26.7 ± 5.0 years (BMI: 22.2 ± 2.5 kg/m2) (mean ± SD) participated. BCAA AUC, and Cmax values were significantly higher with HP than LP (144,765 ± 21,221 vs. 97,089 ± 14,650 µmol·min/L, p < 0.001; 656 ± 120 vs. 407 ± 66 µmol/L, p < 0.001), as were insulin AUC and Cmax values (6674 ± 3013 vs. 5600 ± 2423 µmol·min/L, p = 0.005; 71 ± 37 vs. 55 ± 28 µmol/L, p = 0.001). Higher glucose, urea, and triglyceride concentrations occurred in the late postprandial phase (≥180 min) with HP. In conclusion, we noted that higher milk protein intake induces increased postprandial BCAA concentrations for at least 5 h and led to higher initial insulin secretion. Gluconeogenesis due to an influx of amino acids and their degradation after HP meal might explain the late effects of protein intake on glucose and insulin.


Assuntos
Proteínas na Dieta/sangue , Proteínas na Dieta/farmacologia , Leite/metabolismo , Adulto , Aminoácidos de Cadeia Ramificada/sangue , Animais , Glicemia/metabolismo , Estudos Cross-Over , Proteínas na Dieta/administração & dosagem , Feminino , Humanos , Insulina/sangue , Masculino , Período Pós-Prandial , Triglicerídeos/sangue , Ureia/sangue
17.
ScientificWorldJournal ; 2021: 2173012, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504408

RESUMO

Opuntia dillenii is a medicinal plant with frequent usage in folk medicine to treat many illnesses. The present study aims to investigate the protective effect of Opuntia dillenii seed oil against gentamicin-induced nephrotoxicity in rats. The animals (rats) were randomly divided into three groups (i) the normal control group treated only with distilled water (10 mL/kg), (ii) the gentamicin group treated with distilled water (10 mL/kg) and received an intraperitoneal injection of gentamicin (80 mg/kg), and (iii) the group treated with the Opuntia dillenii seed oil (2 mL/kg) and also received an intraperitoneal injection of gentamicin (80 mg/kg). The rats received their following treatments for 14 consecutive days orally. Serum urea, creatinine, gamma-glutamyl transferase, albumin, and electrolyte levels were quantified as the markers of acute renal and liver failure. Besides, the kidney and liver relative weight, kidney malondialdehydes, and kidney histological analysis were determined. The results have shown that daily pretreatment with Opuntia dillenii seed oil (2 mL/kg) prevented severe alterations of biochemical parameters and disruptions of kidney tissue structures. In addition, the results of the present study showed for the first time that Opuntia dillenii seed oil reduced renal toxicity in gentamicin-induced nephrotoxicity in rats. Therefore, Opuntia dillenii seed oil may represent a new therapeutic avenue to preserve and protect renal function in gentamicin-treated patients.


Assuntos
Antibacterianos/toxicidade , Anti-Inflamatórios/farmacologia , Gentamicinas/antagonistas & inibidores , Rim/efeitos dos fármacos , Nefrite/prevenção & controle , Opuntia/química , Óleos Vegetais/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/isolamento & purificação , Creatinina/sangue , Gentamicinas/toxicidade , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Malondialdeído/metabolismo , Nefrite/induzido quimicamente , Nefrite/metabolismo , Nefrite/patologia , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/química , Óleos Vegetais/isolamento & purificação , Ratos , Ratos Wistar , Sementes/química , Albumina Sérica/metabolismo , Ureia/sangue , gama-Glutamiltransferase/sangue
18.
Nutrients ; 13(9)2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34579066

RESUMO

Nitrogen balance is the difference between nitrogen excreted as urea and nitrogen ingested, mainly in proteins. Increased circulating concentrations of amino acids (AA) in the bloodstream are usually associated with proportional increases in the production and excretion of urea. Previously, we reported results from a randomized, controlled, single-dose, crossover trial in healthy adult volunteers (n = 30) (Trial Registration: ISRCTN11016729), in which a Test product (prolonged-release AA mixture formulated with Physiomimic Technology™ (PT™)) significantly slowed down the release and reduced the peak plasma concentrations of essential AAs compared with a free AA mixture (Reference product) while maintaining essential AA bioavailability. Here, we report an assessment of the nitrogen balance from the same study. The amount of nitrogen contained in plasma AAs, levels of blood urea nitrogen (BUN) (p < 0.0001) and changes in BUN (p < 0.0001) were smaller after the Test product compared with the Reference product. These findings suggest that the production of urea in proportion to systemic AA availability was significantly smaller after the administration of the Test product compared with the Reference product and that the test product conferred the increased utilization of AAs for protein synthesis and reduced their oxidation and conversion to urea. In the clinical setting, it is possible that the effects of PT™ observed on the disposition of free AAs in this study may translate to health benefits in terms of physiological body composition and growth if used for the treatment of subjects with phenylketonuria (PKU). Further investigation in patients with PKU is warranted.


Assuntos
Aminoácidos/administração & dosagem , Nitrogênio da Ureia Sanguínea , Nitrogênio/sangue , Fenilcetonúrias , Proteínas/química , Ureia , Adolescente , Adulto , Aminoácidos/sangue , Aminoácidos Essenciais/sangue , Estudos Cross-Over , Preparações de Ação Retardada , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Fenilcetonúrias/dietoterapia , Método Simples-Cego , Ureia/sangue , Adulto Jovem
19.
Nutrients ; 13(9)2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34579160

RESUMO

Protein imbalance during pregnancy affects women in underdeveloped and developing countries and is associated with compromised offspring growth and an increased risk of metabolic diseases in later life. We studied in a porcine model the glucose and urea metabolism, and circulatory hormone and metabolite profile of offspring exposed during gestation, to maternal isoenergetic low-high (LP-HC), high-low (HP-LC) or adequate (AP) protein-carbohydrate ratio diets. At birth, LP-HC were lighter and the plasma acetylcarnitine to free carnitine ratios at 1 day of life was lower compared to AP offspring. Plasma urea concentrations were lower in 1 day old LP-HC offspring than HP-LC. In the juvenile period, increased insulin concentrations were observed in LP-HC and HP-LC offspring compared to AP, as was body weight from HP-LC compared to LP-HC. Plasma triglyceride concentrations were lower in 80 than 1 day old HP-LC offspring, and glucagon concentrations lower in 80 than 1 day old AP and HP-LC offspring. Plasma urea and the ratio of glucagon to insulin were lower in all 80 than 1 day old offspring. Aminoacyl-tRNA, arginine and phenylalanine, tyrosine and tryptophan metabolism, histidine and beta-alanine metabolism differed between 1 and 80 day old AP and HP-LC offspring. Maternal protein imbalance throughout pregnancy did not result in significant consequences in offspring metabolism compared to AP, indicating enormous plasticity by the placenta and developing offspring.


Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Proteínas na Dieta/administração & dosagem , Fenômenos Fisiológicos da Nutrição Materna , Metaboloma , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Acetilcarnitina/sangue , Animais , Animais Recém-Nascidos/metabolismo , Carnitina/sangue , Carboidratos da Dieta/administração & dosagem , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Masculino , Gravidez , Deficiência de Proteína/metabolismo , Suínos/crescimento & desenvolvimento , Suínos/metabolismo , Triglicerídeos/sangue , Ureia/sangue , Ureia/metabolismo
20.
Med Princ Pract ; 30(6): 557-562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34348300

RESUMO

INTRODUCTION: Sickle cell anaemia is characterized by defective haemoglobin synthesis and is associated with both endocrine and metabolic alterations. The effects of this clinical condition on kidney function are multifactorial and often begin early in childhood. This study aims to assess renal function in children with sickle cell anaemia using urine albumin:creatinine ratio (ACR) and urine human neutrophil gelatinase-associated lipocalin (NGAL). METHODS: This case-control study was conducted on 200 children aged 5-15 years in 2 tertiary hospitals in South West Nigeria: 150 were of haemoglobin S genotype and 50 were of haemoglobin A genotype. Serum urea, creatinine, urine albumin, and NGAL were assayed by known standard methods. eGFR, urine ACR, and urine NGAL/creatinine ratio (urine NCR) were calculated. RESULTS: The weight, height, BMI, systolic blood pressure, plasma urea, plasma creatinine, and spot urine creatinine of the HbS genotype children were significantly lower compared to that of the HbA genotype children. The eGFR, spot urine albumin, and urine ACR were significantly higher in the HbS group compared to the HbA group. There was no significant difference in the spot urine NGAL and urine NCR between the 2 groups, though both were higher in the HbS group compared to the HbA group. CONCLUSIONS: Kidney injury probably starts early in childhood in sickle cell individuals as indicated by the higher urine ACR detected in them. We infer that urine NGAL and uNCR are not sensitive markers of kidney disease especially in young sickle cell individuals possibly because of the hyperfiltration present at this age.


Assuntos
Albuminúria , Anemia Falciforme/sangue , Anemia Falciforme/urina , Creatinina , Rim/metabolismo , Lipocalina-2/urina , Ureia/sangue , Adolescente , Albuminas , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Criança , Pré-Escolar , Creatinina/sangue , Creatinina/urina , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Nigéria
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