Modified Levels of Renin Angiotensin Related Components in the Frontal Cortex and Hippocampus were Associated with Neuroinflammation and Lower Neuroprotective Effects of NGF During Acute Hepatic Encephalopathy in Mice

Natália Katley Oliveira, Eliana Cristina de Brito Toscano, Bruna da Silva Oliveira, Luiza Cioglia Dias Lima, Ana Cristina Simões E Silva, Aline Silva de Miranda, Antônio Lúcio Teixeira, Milene Alvarenga Rachid

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R), which compose the classical pathway of the renin–angiotensin system (RAS), exacerbate neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor, which integrate the alternative RAS axis, have been shown as promising therapeutic targets in neuropsychiatric disorders, leading to neuroprotection. Objective: This study aimed to investigate the potential participation of the RAS components in thioacetamide (TAA)-induced HE in mice. Methods: We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF) were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the chemokine (CCL2) were quantified by cytometric bead array. The student’s t-test was applied for statistical analysis. Results: Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6, IL-12, and CCL2 in the hippocampus compared with controls. Conclusion: This study suggested that the reduction of components of the alternative RAS axis was associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF during TAA-induced HE.

Original languageEnglish (US)
Pages (from-to)1042-1050
Number of pages9
JournalProtein and Peptide Letters
Volume29
Issue number12
DOIs
StatePublished - Dec 2022
Externally publishedYes

Keywords

  • Angiotensin-renin system
  • cytokines
  • hepatic encephalopathy
  • mice
  • neurotrophic factors
  • thioacetamide

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry

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