Pedro Arend Guazzelli

Universidade Federal do Rio Grande do Sul

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Diogo O. Souza

Universidade Federal do Rio Grande do Sul

Adriano Martimbianco de Assis

Universidade Católica de Pelotas

María Elisa Calcagnotto

Universidade Federal do Rio Grande do Sul

Giordano Fabricio Cittolin‐Santos

Washington University in St. Louis

Fernanda U. Fontella

Universidade Federal do Rio Grande do Sul

Roberto Farina Almeida

Universidade Federal de Pelotas

Mayara Vendramin Pasquetti

Universidade Federal do Rio Grande do Sul

Muriel Bossle Sarmento

Hospital de Clínicas de Porto Alegre

Marli Maria Knorst

Universidade Federal do Rio Grande do Sul

Yasmine Nonose

New York Stem Cell Foundation

Cooperative Institutions

Universidade Federal do Rio Grande do Sul

Hospital de Clínicas de Porto Alegre

Universidade Federal de Ciências da Saúde de Porto Alegre

Universidade Federal do Rio Grande

University of Rio Grande and Rio Grande Community College

Hospital de Clínicas

Instituto de Saúde

Hospital Moinhos de Vento

Universidade Católica de Pelotas

Instituto Nacional de Ciência e Tecnologia em Excitotoxicidade e Neuroproteção

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Acute Liver Failure Induces Glial Reactivity, Oxidative Stress and Impairs Brain Energy Metabolism in Rats

Frontiers in Molecular Neuroscience (2020)

Pedro Arend Guazzelli Giordano Fabricio Cittolin‐Santos Leo Anderson Meira-Martins Mateus Grings Yasmine Nonose

Acute liver failure (ALF) implies a severe and rapid liver dysfunction that leads to impaired liver metabolism and hepatic encephalopathy (HE). Recent studies have suggested that several brain alterations such as astrocytic dysfunction and energy metabolism impairment may synergistically interact, playing a role in the development of HE. The purpose of the present study is to investigate early alterations in redox status, energy metabolism and astrocytic reactivity of rats submitted to ALF. Adult male Wistar rats were submitted either to subtotal hepatectomy (92% of liver mass) or sham operation to induce ALF. Twenty-four hours after the surgery, animals with ALF presented higher plasmatic levels of ammonia, lactate, ALT and AST and lower levels of glucose than the animals in the sham group. Animals with ALF presented several astrocytic morphological alterations indicating astrocytic reactivity. The ALF group also presented higher mitochondrial oxygen consumption, higher enzymatic activity and higher ATP levels in the brain (frontoparietal cortex). Moreover, ALF induced an increase in glutamate oxidation concomitant with a decrease in glucose and lactate oxidation. The increase in brain energy metabolism caused by astrocytic reactivity resulted in augmented levels of reactive oxygen species (ROS) and Poly [ADP-ribose] polymerase 1 (PARP1) and a decreased activity of the enzymes superoxide dismutase and glutathione peroxidase (GSH-Px). These findings suggest that in the early stages of ALF the brain presents a hypermetabolic state, oxidative stress and astrocytic reactivity, which could be in part sustained by an increase in mitochondrial oxidation of glutamate.

10.3389/fnmol.2019.00327

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Citations (9)

Guanosine Exerts Neuroprotective Effect in an Experimental Model of Acute Ammonia Intoxication

Molecular Neurobiology (2016)

Giordano Fabricio Cittolin‐Santos Adriano Martimbianco de Assis Pedro Arend Guazzelli Lucas Guazzelli Paim Paniz Jussemara Souza da Silva

10.1007/s12035-016-9892-4

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Citations (14)

Behavioral, Neurochemical and Brain Oscillation Abnormalities in an Experimental Model of Acute Liver Failure

Neuroscience (2019)

Giordano Fabricio Cittolin‐Santos Pedro Arend Guazzelli Yasmine Nonose Roberto Farina Almeida Fernanda U. Fontella

Neurochemical

Hepatic Encephalopathy

Pathophysiology

10.1016/j.neuroscience.2018.12.032

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Citations (7)

Diagnósticos alternativos em pacientes com angiotomografia computadorizada de tórax negativa para tromboembolia pulmonar

Muriel Bossle Sarmento Eleci Vaz Ferreira Pedro Arend Guazzelli Mariana Costa Hoffmeister Luiza Grazziotin Vedana

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Effects of intranasal guanosine administration on brain function in a rat model of ischemic stroke

Purinergic Signalling (2021)

Gabriel Cardozo Müller Samanta Oliveira Loureiro Letícia Ferreira Pettenuzzo Roberto Farina Almeida Evandro Yukio Ynumaru

Stroke

Brain ischemia

10.1007/s11302-021-09766-x

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Citations (9)

Angiotomografia computadorizada de tórax no diagnóstico de tromboembolia pulmonar: adequação técnica e descrição dos principais achados.

Pedro Arend Guazzelli

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Blood-brain barrier permeability and increased levels of amino acids in cerebrospinal fluid are associated with brain alterations in rats with acute liver failure

Research Square (Research Square) (2022)

Pedro Arend Guazzelli Felipe dos Santos Fachim Anderson Santos Travassos Caroline Casagrande Schaukoski Pâmela C.L. Ferreira

Abstract Acute liver failure (ALF) is a life-threatening medical condition that often leads to hepatic encephalopathy (HE). Animals and humans with HE have shown elevated cerebrospinal fluid (CSF) levels of glutamine and glutamate, which may be associated with brain impairment. In this study, we aim to evaluate the relationship between blood-brain barrier (BBB) integrity and CSF amino acid levels with the neurological status of rats after subtotal hepatectomy. Adult male Wistar rats underwent a subtotal hepatectomy (removing 92% of hepatic mass or SHAM group) and were divided into 4 (four) cohorts. Animals with ALF presented severe neurological impairment and high mortality rates when compared to the SHAM group (Cohort 1). We performed a hepatic function test 24 hours after subtotal hepatectomy, which demonstrated a significant increase of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Total Bilirubin, Direct Bilirubin, Prothrombin time and Ammonia levels in blood (Cohort 2). Additionally, the increase of amino acids, glutamine, and albumin levels in CSF as well as of Evans Blue penetration into the brain tissue was correlated with the neurological grades of HE, indicating signs of impaired BBB permeability induced by ALF (Cohort 3). Furthermore, the animals’ mortality rate showed a positive correlation with the increase of amino acid levels in CSF following subtotal hepatectomy (after 12h, Cohort 4). Our data highlight the potential role of amino acid levels in CSF, especially glutamine, for detection purposes even in the early stages of HE and suggest that these molecules offer prognostic value for patients progressing to coma and death.

Hepatic Encephalopathy

10.21203/rs.3.rs-2093824/v1

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Tabagismo em funcionários de um hospital universitário

Muriel Bossle Sarmento Alaíde Mezalira Gusso Tiele Muller Pedro Arend Guazzelli Larissa Nicácio Grimaldi

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Efeitos neuroprotetores da guanosina em modelo de hiperamonemia

Pedro Arend Guazzelli

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