Effects of chronic administration of albumin modified by advanced glycation (age) on liver tissue: characterization of histological, inflammatory and antioxidant profile

• Grant number: 13/00713-7
• Support Opportunities: Scholarships in Brazil - Master
• Effective date (Start): November 01, 2013
• Effective date (End): October 31, 2015
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Maria Lucia Cardillo Corrêa Giannella
• Grantee: Nelly Takashima Fabre
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 12/04831-1 - New players in glycemic control and chronic complications of Diabetes mellitus: preventive and therapeutic perspectives, AP.TEM

Abstract

The Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum that includes simple steatosis and nonalcoholic steatohepatitis and it is considered the hepatic component of the so-called Metabolic Syndrome. Patients with type 2 diabetes mellitus (T2DM) demonstrate greater susceptibility to develop and present progression of NAFLD than non-diabetic subjects: the prevalence of NAFLD in the general population ranges from 17 to 33%, while it seems to be present in up to 70% of T2DM patients. Recently, studies have shown that advanced glycation end products (AGEs) stimulate the production of extracellular matrix proteins and the generation of reactive oxygen species and pro-inflammatory cytokines by liver cells. Our hypothesis is that glycated proteins contribute to metabolic disorders (lipid accumulation, inflammation and oxidative stress) that predispose to the development of liver injury in the spectrum of NAFLD, regardless of hyperglycemia. Thus the aim of this project is to assess whether chronic daily injection (three months) of albumin-AGE modifies the histological, inflammatory and antioxidant profile of the liver tissue and whether treatment with N-acetylcysteine (NAC) attenuates these possible effects. Thus, we will evaluate: the metabolic profile of animals, liver histology and infiltration of Kupffer cells, lipid content, content of reactive oxygen species and the expression of markers of hepatic Kupffer cells M1 (IL-6 , TNF-a) and M2 (IL-10, arginase-1), AGE receptors, pro-inflammatory transcription factor NF-kB, and antioxidant and lipogenic enzymes. Four experimental groups will be assessed: (1) receiving control albumin (20 mg/kg), (2) receiving control albumin + NAC, (3) receiving AGE-albumin (20 mg/kg) and (4) receiving AGE-albumin + NAC. (AU)

Scientific publications

(4)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FABRE, NELLY T.; THIEME, KARINA; SILVA, KAROLLINE S.; CATANOZI, SERGIO; CAVALEIRO, ANA MERCEDES; PINTO, JR., DANILO A. C.; OKAMOTO, MARISTELA M.; MORAIS, MYCHEL RAONY P. T.; FALQUETTO, BARBARA; ZORN, TELMA M.; et al. Hormetic modulation of hepatic insulin sensitivity by advanced glycation end products. Molecular and Cellular Endocrinology, v. 447, n. C, p. 116-124, MAY 15 2017. (12/04831-1, 12/18724-2, 13/00713-7, 14/17251-9)

THIEME, KARINA; DA SILVA, KAROLLINE S.; FABRE, NELLY T.; CATANOZI, SERGIO; MONTEIRO, MARIA BEATRIZ; SANTOS-BEZERRA, DANIELE PEREIRA; COSTA-PESSOA, JULIANA MARTINS; OLIVEIRA-SOUZA, MARIA; MACHADO, UBIRATAN F.; PASSARELLI, MARISA; et al. N-Acetyl Cysteine Attenuated the Deleterious Effects of Advanced Glycation End-Products on the Kidney of Non-Diabetic Rats. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, v. 40, n. 3-4, p. 608-620, 2016. (13/00713-7, 12/04831-1, 14/17251-9, 12/18724-2)

PINTO-JUNIOR, DANILO C.; SILVA, KAROLLINE S.; MICHALANI, MARIA L.; YONAMINE, CAIO Y.; ESTEVES, JOAO V.; FABRE, NELLY T.; THIEME, KARINA; CATANOZI, SERGIO; OKAMOTO, MARISTELA M.; SERAPHIM, PATRICIA M.; et al. Advanced glycation end products-induced insulin resistance involves repression of skeletal muscle GLUT4 expression. SCIENTIFIC REPORTS, v. 8, MAY 25 2018. (12/20432-0, 16/15603-0, 16/25155-5, 12/18724-2, 13/00713-7, 14/17251-9)

THIEME, KARINA; VELOSO PEREIRA, BEATRIZ MARIA; DA SILVA, KAROLLINE S.; FABRE, NELLY T.; CATANOZI, SERGIO; PASSARELLI, MARISA; CORREA-GIANNELLA, MARIA LUCIA. Chronic advanced-glycation end products treatment induces TXNIP expression and epigenetic changes in glomerular podocytes in vivo and in vitro. Life Sciences, v. 270, APR 1 2021. (18/00573-4, 19/10583-0, 16/15603-0, 16/04591-1, 12/04831-1, 12/18724-2, 13/00713-7, 14/17251-9)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FABRE, Nelly Takashima. Effects of chronic administration of albumin modified by advanced glycation (AGE) on the liver tissue: characterization of histological, inflammatory and antioxidant profile. 2016. Master's Dissertation - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.