RESUMO
Kidney disease is a critical and potentially life-threatening degenerative condition that poses a significant global public health challenge due to its elevated rates of morbidity and mortality. It manifests primarily in two distinct clinical forms: acute kidney injury (AKI) and chronic kidney disease (CKD). The development of these conditions hinges on a multitude of factors, including the etiological agents and the presence of coexisting medical conditions. Despite disparities in their underlying pathogenic mechanisms, both AKI and CKD can progress to end-stage kidney disease (ESKD). This advanced stage is characterized by organ failure and its associated complications, greatly increasing the risk of mortality. There is an urgent need to delve into the pathogenic mechanisms underlying these diseases and to identify novel biomarkers that can facilitate earlier diagnosis. Such early detection is crucial for enhancing the efficacy of therapy and impeding disease progression. In this context, proteomic approaches have emerged as invaluable tools for uncovering potential new markers of different pathological conditions, including kidney diseases. In this chapter, we overview the recent discoveries achieved through diverse proteomic techniques aimed at identifying novel molecules that may play a pivotal role in kidney diseases such as diabetic kidney disease (DKD), IgA nephropathy (IgAN), CKD of unknown origin (CKDu), autosomal dominant polycystic kidney disease (ADPKD), lupus nephritis (LN), hypertensive nephropathy (HN), and COVID-19-associated acute kidney injury (COVID-AKI).
Assuntos
Injúria Renal Aguda , Falência Renal Crônica , Insuficiência Renal Crônica , Humanos , Proteômica/métodos , Injúria Renal Aguda/diagnóstico , Diagnóstico Precoce , BiomarcadoresRESUMO
OBJECTIVE: Pressure overload can result in significant changes to the structure of blood vessels, a process known as vascular remodeling. High levels of tension can cause vascular inflammation, fibrosis, and structural alterations to the vascular wall. Prior research from our team has demonstrated that the oral administration of alamandine can promote vasculoprotective effects in mice aorta that have undergone transverse aortic constriction (TAC). Furthermore, changes in local hemodynamics can affect the right and left carotid arteries differently after TAC. Thus, in this study, we aimed to assess the effects of alamandine treatment on right carotid remodeling and the expression of oxidative stress-related substances induced by TAC. METHODS AND RESULTS: Male C57BL/6 mice were categorized into three groups: Sham, TAC, and TAC treated with alamandine (TAC+ALA). Alamandine treatment was administered orally by gavage (30 µg/kg/day), starting three days before the surgery, and continuing for a period of fourteen days. Morphometric analysis of hematoxylin and eosin-stained sections revealed that TAC induced hypertrophic and positive remodeling in the right carotid artery. Picrosirius Red staining also demonstrated an increase in total collagen deposition in the right carotid artery due to TAC-induced vascular changes. Alamandine treatment effectively prevented the increase in reactive oxygen species production and depletion of nitric oxide levels, which were induced by TAC. Finally, alamandine treatment was also shown to prevent the increased expression of nuclear factor erythroid 2-related factor 2 and 3-nitrotyrosine that were induced by TAC. CONCLUSION: Our results suggest that alamandine can effectively attenuate pathophysiological stress in the right carotid artery of animals subjected to TAC.
Assuntos
Artérias Carótidas , Estresse Oxidativo , Masculino , Camundongos , Animais , Constrição , Camundongos Endogâmicos C57BL , Artérias Carótidas/cirurgia , Remodelação Ventricular , Modelos Animais de DoençasRESUMO
Passiflora incarnata L. is a species of global pharmacological importance, has not been fully studied in the context of cultivation and management. It is known that silicon acts on abiotic stress and promotes phenols synthesis. The practice of mechanical damage is widely used in P. incarnata crops, and its interaction with silicon can have a significant influence on plant metabolism. Therefore, our objective was to investigate the effects of silicon and mechanical damage on photosynthesis, polyphenols and vitexin of P. incarnata. The experiment was conducted in a factorial design with SiO2 concentrations (0, 1, 2, 3 mM) and presence or absence of mechanical damage. It was found that mechanical damage improved photosynthetic performance at lower concentrations or absence of silicon. Moreover, this condition promoted an increasing in vitexin concentration when SiO2 was not provided. The application of 3 mM Si is recommended to increase polyphenols and vitexin, without harming dry mass of aerial part. The interaction between silicon and mechanical damage could be a tool to increase agronomic yield and commercial value of the P. incarnata crop.
Assuntos
Apigenina/metabolismo , Passiflora/metabolismo , Polifenóis/metabolismo , Dióxido de Silício/metabolismo , Apigenina/análise , Passiflora/química , Passiflora/crescimento & desenvolvimento , Polifenóis/análise , Silício/metabolismo , Estresse MecânicoRESUMO
AIMS: Exercise training increases circulating and tissue levels of angiotensin-(1-7) [Ang-(1-7)], which was shown to attenuate inflammation and fibrosis in different diseases. Here, we evaluated whether Ang-(1-7)/Mas receptor is involved in the beneficial effects of aerobic training in a chronic model of asthma. MATERIAL AND METHODS: BALB/c mice were subjected to a protocol of asthma induced by ovalbumin sensitization (OVA; 4 i.p. injections) and OVA challenge (3 times/week for 4 weeks). Simultaneously to the challenge period, part of the animals was continuously treated with Mas receptor antagonist (A779, 1 µg/h; for 28 days) and trained in a treadmill (TRE; 60% of the maximal capacity, 1 h/day, 5 days/week during 4 weeks). PGC1-α mRNA expression (qRT-PCR), plasma IgE and lung cytokines (ELISA), inflammatory cells infiltration (enzymatic activity assay) and airway remodeling (by histology) were evaluated. KEY FINDINGS: Blocking the Mas receptor with A779 increased IgE and IL-13 levels and prevented the reduction in extracellular matrix deposition in airways in OVA-TRE mice. Mas receptor blockade prevented the reduction of myeloperoxidase activity, as well as, prevented exercise-induced IL-10 increase. These data show that activation of Ang-(1-7)/Mas receptor pathway is involved in the anti-inflammatory and anti-fibrotic effects of aerobic training in an experimental model of chronic asthma. SIGNIFICANCE: Our results support exercise training as a non-pharmacological tool to defeat lung remodeling induced by chronic pulmonary inflammation. Further, our result also supports development of new therapy based on Ang-(1-7) or Mas agonists as important tool for asthma treatment in those patients that cannot perform aerobic training.
Assuntos
Angiotensina I/metabolismo , Asma/terapia , Fragmentos de Peptídeos/metabolismo , Pneumonia/terapia , Angiotensina I/sangue , Animais , Asma/sangue , Asma/metabolismo , Modelos Animais de Doenças , Terapia por Exercício , Masculino , Camundongos Endogâmicos BALB C , Fragmentos de Peptídeos/sangue , Pneumonia/sangue , Pneumonia/metabolismoRESUMO
Alamandine is the newest identified peptide of the renin-angiotensin system (RAS) and has protective effects in the cardiovascular system. Although the involvement of classical RAS components in the genesis and progression of cardiac remodeling is well known, less is known about the effects of alamandine. Therefore, in the present study we investigated the effects of alamandine on cardiac remodeling induced by transverse aortic constriction (TAC) in mice. Male mice (C57BL/6), 10-12 wk of age, were divided into three groups: sham operated, TAC, and TAC + ALA (30 µg/kg/day alamandine for 14 days). The TAC surgery was performed under ketamine and xylazine anesthesia. At the end of treatment, the animals were submitted to echocardiographic examination and subsequently euthanized for tissue collection. TAC induced myocyte hypertrophy, collagen deposition, and the expression of matrix metalloproteinase (MMP)-2 and transforming growth factor (TGF)-ß in the left ventricle. These markers of cardiac remodeling were reduced by oral treatment with alamandine. Western blotting analysis showed that alamandine prevents the increase in ERK1/2 phosphorylation and reverts the decrease in 5'-adenosine monophosphate-activated protein kinase (AMPK)α phosphorylation induced by TAC. Although both TAC and TAC + ALA increased SERCA2 expression, the phosphorylation of phospholamban in the Thr17 residue was increased solely in the alamandine-treated group. The echocardiographic data showed that there are no functional or morphological alterations after 2 wk of TAC. Alamandine treatment prevents myocyte hypertrophy and cardiac fibrosis induced by TAC. Our results reinforce the cardioprotective role of alamandine and highlight its therapeutic potential for treating heart diseases related to pressure overload conditions.NEW & NOTEWORTHY Alamandine is the newest identified component of the renin-angiotensin system protective arm. Considering the beneficial effects already described so far, alamandine is a promising target for cardiovascular disease treatment. We demonstrated for the first time that alamandine improves many aspects of cardiac remodeling induced by pressure overload, including cell hypertrophy, fibrosis, and oxidative stress markers.
Assuntos
Fármacos Cardiovasculares/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Hipertrofia Ventricular Esquerda/prevenção & controle , Oligopeptídeos/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Aorta/fisiopatologia , Aorta/cirurgia , Proteínas de Ligação ao Cálcio/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/fisiopatologia , Ligadura , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismoRESUMO
NEW FINDINGS: What is the central question of this study? How does swimming exercise training impact hydro-electrolytic balance, renal function, sympathetic contribution to resting blood pressure and cerebrospinal fluid (CSF) [Na+ ] in rats fed a high-sodium diet from weaning? What is the main finding and its importance? An exercise-dependent reduction in blood pressure was associated with decreased CSF [Na+ ], sympathetically driven vasomotor tonus and renal fibrosis indicating that the anti-hypertensive effects of swimming training in rats fed a high-sodium diet might involve neurogenic mechanisms regulated by sodium levels in the CSF rather than changes in blood volume. ABSTRACT: High sodium intake is an important factor associated with hypertension. High-sodium intake with exercise training can modify homeostatic hydro-electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na+ concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na+ (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high-sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF [Na+ ] levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro-electrolytic balance, which might involve neurogenic mechanisms regulated by Na+ levels in the CSF as well as renal protection.
Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Pressão Sanguínea/fisiologia , Hipertensão/fisiopatologia , Rim/fisiopatologia , Sódio na Dieta , Animais , Sistema Nervoso Autônomo/patologia , Dieta , Frequência Cardíaca/fisiologia , Hipertensão/patologia , Rim/patologia , Masculino , Condicionamento Físico Animal , Ratos , Ratos Wistar , Natação , Equilíbrio HidroeletrolíticoRESUMO
Acute Kidney Injury (AKI) comprises a rapidly developed renal failure and is associated with high mortality rates. The Renin-Angiotensin System (RAS) plays a pivotal role in AKI, as the over-active RAS axis exerts major deleterious effects in disease progression. In this sense, the conversion of Angiotensin II (Ang II) into Angiotensin-(1-7) (Ang-(1-7)) by the Angiotensin-converting enzyme 2 (ACE2) is of utmost importance to prevent worse clinical outcomes. Previous studies reported the beneficial effects of oral diminazene aceturate (DIZE) administration, an ACE2 activator, in renal diseases models. In the present study, we aimed to evaluate the therapeutic effects of DIZE administration in experimental AKI induced by gentamicin (GM) in rats. Our findings showed that treatment with DIZE improved renal function and tissue damage by increasing Ang-(1-7) and ACE2 activity, and reducing TNF-α. These results corroborate with a raising potential of ACE2 activation as a strategy for treating AKI.
Assuntos
Injúria Renal Aguda/tratamento farmacológico , Injúria Renal Aguda/enzimologia , Enzima de Conversão de Angiotensina 2/metabolismo , Diminazena/análogos & derivados , Ativadores de Enzimas/farmacologia , Gentamicinas/efeitos adversos , Rim/patologia , Substâncias Protetoras/uso terapêutico , Injúria Renal Aguda/fisiopatologia , Injúria Renal Aguda/urina , Animais , Biomarcadores/metabolismo , Peso Corporal/efeitos dos fármacos , Citocinas/metabolismo , Diminazena/farmacologia , Diminazena/uso terapêutico , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/fisiopatologia , Masculino , Substâncias Protetoras/farmacologia , Ratos Wistar , Sistema Renina-AngiotensinaRESUMO
AIM: This study determined the optimum gamma irradiation dosage to sterilize sodium hyaluronate (HY), single-walled carbon nanotubes (SWCNT), multi-walled carbon nanotubes (MWCNT) and CNT functionalized with HY (HY-SWCNT and HY-MWCNT), evaluated the structural integrity of the materials and assessed whether sterilized materials kept biological properties without affecting renal function. MAIN METHODS: Materials were submitted to dosages of 100 gγ to 30 Kgγ and plated onto agar mediums for colony forming units (CFUs) counting. Sterilized samples were inoculated with 107Bacillus clausii, submitted again to gamma irradiation, and plated in agar mediums for CFUs counting. Scanning electron microscope was used for structural evaluation of sterilized materials. Tooth sockets of rats were treated with sterilized materials for bone formation assessment and renal function of the animals was analyzed. KEY FINDINGS: The optimum gamma dosage for sterilization was 250 gγ for HY and 2.5 Kgγ for the other materials without meaningful structural changes. Sterilized materials significantly increased bone formation (p < 0.05) and they did not compromise renal function and structure. SIGNIFICANCE: Gamma irradiation efficiently sterilized HY, SWCNT, MWCNT, HY-SWCNT and HY-MWCNT without affecting structural aspects while maintaining their desirable biological properties.
Assuntos
Materiais Dentários/efeitos da radiação , Raios gama , Ácido Hialurônico/efeitos da radiação , Nanotubos de Carbono/efeitos da radiação , Osteogênese/efeitos dos fármacos , Alvéolo Dental/efeitos dos fármacos , Animais , Bacillus clausii/efeitos da radiação , Contagem de Colônia Microbiana , Materiais Dentários/química , Materiais Dentários/farmacologia , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Testes de Função Renal , Masculino , Dente Molar/cirurgia , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Ratos , Ratos Wistar , Esterilização/métodos , Extração Dentária/métodos , Alvéolo Dental/microbiologia , Alvéolo Dental/fisiologia , Alvéolo Dental/cirurgia , Cicatrização/efeitos dos fármacosRESUMO
AIMS: To investigate the effects of moderate aerobic physical training on cardiac function and morphology as well as on the levels of glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) of animals infected with the Y strain of Trypanosoma cruzi. MAIN METHODS: Twenty-eight male C57BL/6 mice were distributed into 4 groups: sedentary control (SC), trained control (TC), sedentary infected (CHC) and trained infected (CHT). The infection was performed by intraperitoneal injection of trypomastigote forms and the animals were adapted to treadmill in the week before the beginning of the training protocol, initiated 45â¯days post infection. Maximal exercise test (TEM) was performed at the baseline as well as at the end of the 4th, 8th and 12th weeks of training. At the end of the 12th week, all animals were evaluated for cardiac morphology and function by echocardiography. KEY FINDINGS: CHC group showed a larger area of right ventricle (RVA), increased end-systolic volume and reduction in ejection fraction (EF), stroke volume (SV), cardiac output (CO) and fractional area change (FAC). The training reduced the RVA and improved the FAC of chagasic animals. GDNF level was higher in TC and CHC groups compared to SC in heart and BDNF levels were higher in CHC compared to SC in heart and serum. SIGNIFICANCE: Physical training ameliorated the cardiac function of infected animals and promoted adjusts in BDNF and GDNF levels. These findings evidenced these neurotrophins as possible biomarkers of cardiac function responsive to exercise stimulus.
Assuntos
Tolerância ao Exercício/fisiologia , Condicionamento Físico Animal/métodos , Condicionamento Físico Animal/fisiologia , Animais , Biomarcadores/sangue , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/fisiologia , Débito Cardíaco , Doença de Chagas/metabolismo , Modelos Animais de Doenças , Ecocardiografia , Teste de Esforço , Fator Neurotrófico Derivado de Linhagem de Célula Glial/análise , Fator Neurotrófico Derivado de Linhagem de Célula Glial/fisiologia , Coração/fisiologia , Testes de Função Cardíaca , Ventrículos do Coração/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fator de Crescimento Neural/análise , Fator de Crescimento Neural/fisiologia , Fatores de Crescimento Neural/metabolismo , Fatores de Crescimento Neural/fisiologia , Volume Sistólico/fisiologia , Trypanosoma cruzi/patogenicidadeRESUMO
The concentration of nitrogen can generate different strategies in plants in response to stress. In this study, we investigated how nitrogen concentration interferes with the defense system of Annona emarginata. Low concentrations of nitrogen increased the allocation of photosynthetic resources to carbon metabolism, resulting in an increase in the synthesis of volatile substances involved in signaling and defense that contributed to antioxidant enzymes in overcoming stress. The availability of nitrogen at 5.62 mM concentration might have helped to induce increased resistance in the plants because at this concentration, signaling substances and defense substances (monoterpenes and sesquiterpenes) were observed. Plants cultivated with the highest nitrate concentration displaced energy for the reduction of this ion, likely forming nitric oxide, a signaling molecule. This condition, together with the decrease in carbon skeletons, may have contributed to the lower synthesis of volatile substances of the specialized metabolism that are also involved with signaling. Varying the nitrogen in Annona emarginata cultivation revealed that depending on the concentration, volatile substances show higher or lower synthesis and participation in the system of signaling and defense in the plant. These results may suggest that volatile substances participate in resistance to pests and diseases, which is a necessary condition for Annona emarginata to be preferentially used as rootstock for Annona x atemoya.