Diogo Barros Peruchetti

@ufmg.br

Associate Professor at Department of Physiology and Biophysics from Biological Science Institue
Federal University of Minas Gerais



              

https://researchid.co/dperuchetti

RESEARCH, TEACHING, or OTHER INTERESTS

Physiology, Biophysics, Biochemistry, Cell Biology

37

Scopus Publications

Scopus Publications

  • Preconditioning by Moderate-Intensity Exercise Prevents Gentamicin-Induced Acute Kidney Injury
    Esdras Guedes Fonseca, Ana Paula Araújo-Ferreira, Markus Berger, Leda Maria Castro Coimbra-Campos, Roberta Silva Filha, Leticia Maria de Souza Cordeiro, Mariana Rodrigues Campos, Laura Barroso Ferreira Oliveira, Marcelo Vidigal Caliari, Lucio Ricardo Leite Diniz,et al.
    Georg Thieme Verlag KG
    AbstractA strict correlation among proximal tubule epithelial cell dysfunction, proteinuria, and modulation of the Renin-Angiotensin System and Kalikrein-Kinin System are crucial factors in the pathogenesis of Acute Kidney Injury (AKI). In this study, we investigated the potential protective effect of preconditioning by moderate-intensity aerobic exercise on gentamicin-induced AKI. Male Wistar rats were submitted to a moderate-intensity treadmill exercise protocol for 8 weeks, and then injected with 80 mg/kg/day s.c. gentamicin for 5 consecutive days. Four groups were generated: 1) NT+SAL (control); 2) NT+AKI (non-trained with AKI); 3) T+SAL (trained); and 4) T+AKI (trained with AKI). The NT+AKI group presented: 1) impairment in glomerular function parameters; 2) increased fractional excretion of Na + , K + , and water; 4) proteinuria and increased urinary γ-glutamyl transferase activity (a marker of tubular injury) accompanied by acute tubular necrosis; 5) an increased renal angiotensin-converting enzyme and bradykinin B1 receptor mRNA expression. Interestingly, the preconditioning by moderate-intensity aerobic exercise attenuated all alterations observed in gentamicin-induced AKI (T+AKI group). Taken together, our results show that the preconditioning by moderate-intensity aerobic exercise ameliorates the development of gentamicin-induced AKI. Our findings help to expand the current knowledge regarding the effect of physical exercise on kidneys during physiological and pathological conditions.

  • The angiotensin II/type 1 angiotensin II receptor pathway is implicated in the dysfunction of albumin endocytosis in renal proximal tubule epithelial cells induced by high glucose levels
    Liz G. Afonso, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Sarah A.S. Alves, Alvin H. Schmaier, Ana Acacia S. Pinheiro, Diogo B. Peruchetti, and Celso Caruso-Neves
    Elsevier BV

  • Interaction of Angiotensin-(1−7) with kinins in the kidney circulation: Role of B<inf>1</inf> receptors
    Elizabeth Pereira Mendes, Danielle Ianzer, Diogo Barros Peruchetti, Robson Augusto Souza Santos, and Maria Aparecida Ribeiro Vieira
    Elsevier BV

  • Toll like receptor 4 mediates the inhibitory effect of SARS-CoV-2 spike protein on proximal tubule albumin endocytosis
    Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Rodrigo A.S. Peres, Sarah A.S. Alves, Pedro T. Calil, Luciana B. Arruda, Luciana J. Costa, Pedro L. Silva, Alvin H. Schmaier,et al.
    Elsevier BV

  • Receptor-mediated endocytosis in kidney cells during physiological and pathological conditions
    Mariana C. Rodrigues, Laura B.F. Oliveira, Maria Aparecida R. Vieira, Celso Caruso-Neves, and Diogo B. Peruchetti
    Elsevier

  • Kidney Disease and Proteomics: A Recent Overview of a Useful Tool for Improving Early Diagnosis
    Nicolly Emanuelle de Souza Barcelos, Maria Laura Limeres, Ana Flavia Peixoto-Dias, Maria Aparecida Ribeiro Vieira, and Diogo B. Peruchetti
    Springer International Publishing

  • Multi-omics Investigations in Endocrine Systems and Their Clinical Implications
    Rodrigo Antonio Peliciari-Garcia, Carolina Fonseca de Barros, Ayla Secio-Silva, Diogo de Barros Peruchetti, Renata Marino Romano, and Paula Bargi-Souza
    Springer International Publishing

  • Bradykinin produced during Plasmodium falciparum erythrocytic cycle drives monocyte adhesion to human brain microvascular endothelial cells
    Sarah A.S. Alves, Douglas E. Teixeira, Diogo B. Peruchetti, Leandro S. Silva, Luiz Felipe P. Brandão, Celso Caruso-Neves, and Ana Acacia S. Pinheiro
    Elsevier BV

  • O-Linked GlcNAcylation mediates the inhibition of proximal tubule (Na<sup>+</sup>+K<sup>+</sup>)ATPase activity in the early stage of diabetes mellitus
    Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A.S. Peres, Sarah A.S. Alves, Carolina Novaes-Fernandes, Wagner B. Dias, Ana Acacia S. Pinheiro, Diogo B. Peruchetti, and Celso Caruso-Neves
    Elsevier BV

  • Gold nanoparticles reduce tubule-interstitial injury and proteinuria in a murine model of subclinical acute kidney injury
    Rodrigo A.S. Peres, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Sarah A.S. Alves, Anna Beatriz C. Leal, Guilherme F. Castro, Natalia B.S. Ribeiro, Fernanda V. Guimarães, Ana Acacia S. Pinheiro,et al.
    Elsevier BV

  • Inhibition of SGLT2 co-transporter by dapagliflozin ameliorates tubular proteinuria and tubule-interstitial injury at the early stage of diabetic kidney disease
    Raysa S. Farias, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Carlos P. Gomes, Ana Acacia S. Pinheiro, Diogo B. Peruchetti, and Celso Caruso-Neves
    Elsevier BV

  • Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption
    Rodrigo A. S. Peres, Diogo B. Peruchetti, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Carlos P. Gomes, Christina M. Takiya, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    Frontiers Media SA
    Introduction: Rapamycin is an immunosuppressor that acts by inhibiting the serine/threonine kinase mechanistic target of rapamycin complex 1. Therapeutic use of rapamycin is limited by its adverse effects. Proteinuria is an important marker of kidney damage and a risk factor for kidney diseases progression and has been reported in patients and animal models treated with rapamycin. However, the mechanism underlying proteinuria induced by rapamycin is still an open matter. In this work, we investigated the effects of rapamycin on parameters of renal function and structure and on protein handling by proximal tubule epithelial cells (PTECs).Methods: Healthy BALB/c mice were treated with 1.5 mg/kg rapamycin by oral gavage for 1, 3, or 7 days. At the end of each treatment, the animals were kept in metabolic cages and renal function and structural parameters were analyzed. LLC-PK1 cell line was used as a model of PTECs to test specific effect of rapamycin.Results: Rapamycin treatment did not change parameters of glomerular structure and function. Conversely, there was a transient increase in 24-h proteinuria, urinary protein to creatinine ratio (UPCr), and albuminuria in the groups treated with rapamycin. In accordance with these findings, rapamycin treatment decreased albumin-fluorescein isothiocyanate uptake in the renal cortex. This effect was associated with reduced brush border expression and impaired subcellular distribution of megalin in PTECs. The effect of rapamycin seems to be specific for albumin endocytosis machinery because it did not modify renal sodium handling or (Na++K+)ATPase activity in BALB/c mice and in the LLC-PK1 cell line. A positive Pearson correlation was found between megalin expression and albumin uptake while an inverse correlation was shown between albumin uptake and UPCr or 24-h proteinuria. Despite its effect on albumin handling in PTECs, rapamycin treatment did not induce tubular injury measured by interstitial space and collagen deposition.Conclusion: These findings suggest that proteinuria induced by rapamycin could have a tubular rather than a glomerular origin. This effect involves a specific change in protein endocytosis machinery. Our results open new perspectives on understanding the undesired effect of proteinuria generated by rapamycin.

  • SARS-CoV-2 spike protein inhibits megalin-mediated albumin endocytosis in proximal tubule epithelial cells
    Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Diogo B. Peruchetti, Lucas S. Florentino, Rodrigo A.S. Peres, Carlos P. Gomes, Maria-Paz Marzolo, Patricia M.R. Rocco, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    Elsevier BV

  • Subclinical Acute Kidney Injury in COVID-19: Possible Mechanisms and Future Perspectives
    Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Rodrigo A. S. Peres, Diogo B. Peruchetti, Carlos P. Gomes, Alvin H. Schmaier, Patricia R. M. Rocco, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    MDPI AG
    Since the outbreak of COVID-19 disease, a bidirectional interaction between kidney disease and the progression of COVID-19 has been demonstrated. Kidney disease is an independent risk factor for mortality of patients with COVID-19 as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to the development of acute kidney injury (AKI) and chronic kidney disease (CKD) in patients with COVID-19. However, the detection of kidney damage in patients with COVID-19 may not occur until an advanced stage based on the current clinical blood and urinary examinations. Some studies have pointed out the development of subclinical acute kidney injury (subAKI) syndrome with COVID-19. This syndrome is characterized by significant tubule interstitial injury without changes in the estimated glomerular filtration rate. Despite the complexity of the mechanism(s) underlying the development of subAKI, the involvement of changes in the protein endocytosis machinery in proximal tubule (PT) epithelial cells (PTECs) has been proposed. This paper focuses on the data relating to subAKI and COVID-19 and the role of PTECs and their protein endocytosis machinery in its pathogenesis.

  • O-GlcNAcylation in Renal (Patho)Physiology
    Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Ana Acacia S. Pinheiro, Celso Caruso-Neves, and Wagner B. Dias
    MDPI AG
    Kidneys maintain internal milieu homeostasis through a well-regulated manipulation of body fluid composition. This task is performed by the correlation between structure and function in the nephron. Kidney diseases are chronic conditions impacting healthcare programs globally, and despite efforts, therapeutic options for its treatment are limited. The development of chronic degenerative diseases is associated with changes in protein O-GlcNAcylation, a post-translation modification involved in the regulation of diverse cell function. O-GlcNAcylation is regulated by the enzymatic balance between O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) which add and remove GlcNAc residues on target proteins, respectively. Furthermore, the hexosamine biosynthetic pathway provides the substrate for protein O-GlcNAcylation. Beyond its physiological role, several reports indicate the participation of protein O-GlcNAcylation in cardiovascular, neurodegenerative, and metabolic diseases. In this review, we discuss the impact of protein O-GlcNAcylation on physiological renal function, disease conditions, and possible future directions in the field.

  • The monoterpene 1,8-cineole prevents cerebral edema in a murine model of severe malaria
    Edgleyson C. dos Santos, Leandro S. Silva, Alessandro S. Pinheiro, Douglas E. Teixeira, Diogo B. Peruchetti, Rodrigo P. Silva-Aguiar, Camila H. C. Wendt, Kildare R. Miranda, Andrelina N. Coelho-de-Souza, José Henrique Leal-Cardoso,et al.
    Public Library of Science (PLoS)
    1,8-Cineole is a naturally occurring compound found in essential oils of different plants and has well-known anti-inflammatory and antimicrobial activities. In the present work, we aimed to investigate its potential antimalarial effect, using the following experimental models: (1) the erythrocytic cycle of Plasmodium falciparum; (2) an adhesion assay using brain microvascular endothelial cells; and (3) an experimental cerebral malaria animal model induced by Plasmodium berghei ANKA infection in susceptible mice. Using the erythrocytic cycle of Plasmodium falciparum, we characterized the schizonticidal effect of 1,8-cineole. This compound decreased parasitemia in a dose-dependent manner with a half maximal inhibitory concentration of 1045.53 ± 63.30 μM. The inhibitory effect of 972 μM 1,8-cineole was irreversible and independent of parasitemia. Moreover, 1,8-cineole reduced the progression of intracellular development of the parasite over 2 cycles, inducing important morphological changes. Ultrastructure analysis revealed a massive loss of integrity of endomembranes and hemozoin crystals in infected erythrocytes treated with 1,8-cineole. The monoterpene reduced the adhesion index of infected erythrocytes to brain microvascular endothelial cells by 60%. Using the experimental cerebral malaria model, treatment of infected mice for 6 consecutive days with 100 mg/kg/day 1,8-cineole reduced cerebral edema with a 50% reduction in parasitemia. Our data suggest a potential antimalarial effect of 1,8-cineole with an impact on the parasite erythrocytic cycle and severe disease.

  • Albumin Expands Albumin Reabsorption Capacity in Proximal Tubule Epithelial Cells through a Positive Feedback Loop between AKT and Megalin
    Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Lucas S. Florentino, Christina M. Takiya, María-Paz Marzolo, Wagner B. Dias, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    MDPI AG
    Renal proximal tubule cells (PTECs) act as urine gatekeepers, constantly and efficiently avoiding urinary protein waste through receptor-mediated endocytosis. Despite its importance, little is known about how this process is modulated in physiologic conditions. Data suggest that the phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT) pathway regulates PTEC protein reabsorption. Here, we worked on the hypothesis that the physiologic albumin concentration and PI3K/AKT pathway form a positive feedback loop to expand endocytic capacity. Using LLC-PK1 cells, a model of PTECs, we showed that the PI3K/AKT pathway is required for megalin recycling and surface expression, affecting albumin uptake. Inhibition of this pathway stalls megalin at EEA1+ endosomes. Physiologic albumin concentration (0.01 mg/mL) activated AKT; this depends on megalin-mediated albumin endocytosis and requires previous activation of PI3K/mTORC2. This effect is correlated to the increase in albumin endocytosis, a phenomenon that we refer to as “albumin-induced albumin endocytosis”. Mice treated with L-lysine present decreased albumin endocytosis leading to proteinuria and albuminuria associated with inhibition of AKT activity. Renal cortex explants obtained from control mice treated with MK-2206 decreased albumin uptake and promoted megalin internalization. Our data highlight the mechanism behind the capacity of PTECs to adapt albumin reabsorption to physiologic fluctuations in its filtration, avoiding urinary excretion.

  • Surface megalin expression is a target to the inhibitory effect of bradykinin on the renal albumin endocytosis
    Sarah A.S. Alves, Lucas S. Florentino, Douglas E. Teixeira, Rodrigo P. Silva-Aguiar, Diogo B. Peruchetti, Ana Carolina Oliveira, Julio Scharfstein, María-Paz Marzolo, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    Elsevier BV

  • Megalin-mediated albumin endocytosis in renal proximal tubules is involved in the antiproteinuric effect of angiotensin II type 1 receptor blocker in a subclinical acute kidney injury animal model
    Diogo B. Peruchetti, Paulo F.R. Barahuna-Filho, Rodrigo P. Silva-Aguiar, Thiago P. Abreu, Christina M. Takiya, Jie Cheng, Ana Acacia S. Pinheiro, Liudmila Cebotaru, William B. Guggino, and Celso Caruso-Neves
    Elsevier BV

  • High doses of essential oil of croton zehntneri induces renal tubular damage
    Katarine F. Silva, Diogo B. Peruchetti, Gabriela M. Sirtoli, Christina M. Takiya, Ana Acacia S. Pinheiro, José Henrique Leal-Cardoso, and Celso Caruso-Neves
    MDPI AG
    The essential oil of Croton zehntneri (EOCZ) and its major compounds are known to have several biological activities. However, some evidence shows potential toxic effects of high doses of EOCZ (&gt;300 mg/kg) in amphibian and human kidneys. The aim of the present work was to investigate the effects on renal function of EOCZ at 300 mg/kg/day in healthy Swiss mice and a subclinical acute kidney injury (subAKI) animal model, which presents tubule-interstitial injury (TII). Four experimental groups were generated: (1) CONT group (control); (2) EOCZ, mice treated with EOCZ; (3) subAKI; (4) subAKI+EOCZ, subAKI treated simultaneously with EOCZ. EOCZ treatment induced TII measured by increases in (1) proteinuria; (2) cortical tubule-interstitial space; (3) macrophage infiltration; (4) collagen deposition. A decrease in tubular sodium reabsorption was also observed. These results were similar and nonadditive to those observed in the subAKI group. These data suggest that treatment with EOCZ at higher concentrations induces TII in mice, which could be mediated by protein overload in the proximal tubule.

  • Eugenol disrupts Plasmodium falciparum intracellular development during the erythrocytic cycle and protects against cerebral malaria
    Kesley A.O. Pontes, Leandro S. Silva, Edgleyson C. Santos, Alessandro S. Pinheiro, Douglas E. Teixeira, Diogo B. Peruchetti, Rodrigo P. Silva-Aguiar, Camila H.C. Wendt, Kildare R. Miranda, Andrelina N. Coelho-de-Souza,et al.
    Elsevier BV

  • A high salt diet induces tubular damage associated with a pro-inflammatory and pro-fibrotic response in a hypertension-independent manner
    Douglas Esteves Teixeira, Diogo B. Peruchetti, Mariana C. Souza, Maria G. das Graças Henriques, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    Elsevier BV

  • The renin–angiotensin–aldosterone system: Role in pathogenesis and potential therapeutic target in COVID-19
    Cássia L. Braga, Rodrigo P. Silva‐Aguiar, Denise Battaglini, Diogo B. Peruchetti, Chiara Robba, Paolo Pelosi, Patricia R. M. Rocco, Celso Caruso‐Neves, and Pedro L. Silva
    Wiley
    AbstractCoronavirus disease 2019 (COVID‐19), caused by the SARS‐CoV‐2 novel coronavirus, has spread worldwide causing high fatality rates. Neither a vaccine nor specific therapeutic approaches are available, hindering the fight against this disease and making better understanding of its pathogenesis essential. Despite similarities between SARS‐CoV‐2 and SARS‐CoV, the former has unique characteristics which represent a great challenge to physicians. The mechanism of COVID‐19 infection and pathogenesis is still poorly understood. In the present review, we highlight possible pathways involved in the pathogenesis of COVID‐19 and potential therapeutic targets, focusing on the role of the renin–angiotensin–aldosterone system.

  • IL-4 Receptor α Chain Protects the Kidney Against Tubule-Interstitial Injury Induced by Albumin Overload
    Diogo B. Peruchetti, João Luiz Silva-Filho, Rodrigo P. Silva-Aguiar, Douglas E. Teixeira, Christina M. Takiya, Mariana C. Souza, Maria das Graças Henriques, Ana Acacia S. Pinheiro, and Celso Caruso-Neves
    Frontiers Media SA
    Increasing evidence has highlighted the role of tubule-interstitial injury (TII) as a vital step in the pathogenesis of acute kidney injury (AKI). Incomplete repair of TII during AKI could lead to the development of chronic kidney disease. Changes in albumin endocytosis in proximal tubule epithelial cells (PTECs) is linked to the development of TII. In this context, interleukin (IL)-4 has been shown to be an important factor in modulating recovery of TII. We have studied the possible role of IL-4 in TII induced by albumin overload. A subclinical AKI model characterized by albumin overload in the proximal tubule was used, without changing glomerular function. Four groups were generated: (1) CONT, wild-type mice treated with saline; (2) BSA, wild-type mice treated with 10 g/kg/day bovine serum albumin (BSA); (3) KO, IL4Rα–/– mice treated with saline; and (4) KO + BSA, IL4Rα–/– mice treated with BSA. As reported previously, mice in the BSA group developed TII without changes in glomerular function. The following parameters were increased in the KO + BSA group compared with the BSA group: (1) tubular injury score; (2) urinary γ-glutamyltransferase; (3) CD4+ T cells, dendritic cells, macrophages, and neutrophils are associated with increases in renal IL-6, IL-17, and transforming growth factor β. A decrease in M2-subtype macrophages associated with a decrease in collagen deposition was observed. Using LLC-PK1 cells, a model of PTECs, we observed that (1) these cells express IL-4 receptor α chain associated with activation of the JAK3/STAT6 pathway; (2) IL-4 alone did not change albumin endocytosis but did reverse the inhibitory effect of higher albumin concentration. This effect was abolished by JAK3 inhibitor. A further increase in urinary protein and creatinine levels was observed in the KO + BSA group compared with the BSA group, but not compared with the CONT group. These observations indicate that IL-4 has a protective role in the development of TII induced by albumin overload that is correlated with modulation of the pro-inflammatory response. We propose that megalin-mediated albumin endocytosis in PTECs could work as a sensor, transducer, and target during the genesis of TII.

  • Role of the renin-angiotensin system in the development of severe COVID-19 in hypertensive patients
    Rodrigo Pacheco Silva-Aguiar, Diogo Barros Peruchetti, Patricia Rieken Macedo Rocco, Alvin H. Schmaier, Patrícia Machado Rodrigues e Silva, Marco Aurélio Martins, Vinícius Frias Carvalho, Ana Acacia Sá Pinheiro, and Celso Caruso-Neves
    American Physiological Society
    A new form of severe acute respiratory syndrome (SARS) caused by SARS-coronavirus 2 (CoV-2), called COVID-19, has become a global threat in 2020. The mortality rate from COVID-19 is high in hypertensive patients, making this association especially dangerous. There appears to be a consensus, despite the lack of experimental data, that angiotensin II (ANG II) is linked to the pathogenesis of COVID-19. This process may occur due to acquired deficiency of angiotensin-converting enzyme 2 (ACE2), resulting in reduced degradation of ANG II. Furthermore, ANG II has a critical role in the genesis and worsening of hypertension. In this context, the idea that there is a surge in the level of ANG II with COVID-19 infection, causing multiple organ injuries in hypertensive patients becomes attractive. However, the role of other components of the renin angiotensin system (RAS) in this scenario requires elucidation. The identification of other RAS components in COVID-19 hypertension may provide both diagnostic and therapeutic benefits. Here, we summarize the pathophysiologic contributions of different components of RAS in hypertension and their possible correlation with poor outcome observed in hypertensive patients with COVID-19.