Functional alterations of hepatic mitochondria in lipopolysaccharide tolerance (LPS)

Author(s)

André Augusto Botêga Silva

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD)
• Defense date: 2017-10-27

Examining board members

Francisco Garcia Soriano; Maria Fernanda Cury Boaventura; Fabiano Pinheiro da Silva

• Advisor: Francisco Garcia Soriano

Abstract

The aim of this study was to evaluate the early functional alterations of hepatic mitochondria of wistar rats submitted to the stimulation of sepsis through the technique of cecal ligation and puncture (CLP) and induction of tolerance to lipopolysaccharide (LPS) of Escherichia coli. Mitochondria play a role in altering the cellular metabolism of septic patients. The objectives of the present study were: (1) to standardize the tolerance induction technique for wistar rats with E. coli LPS (2) to evaluate the mitochondrial phosphorylation and oxidative function; (3) quantify mitochondrial DNA in hepatic tissue of animals submitted to CPL and tolerance; (4) to verify the expression of genes responsible for mitochondria biogenesis and mitochondrial DNA replication nuclear mitochondrial biogenesis (NRF-1), mitochondrial transcription factor A (TFAM) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha); (5) to evaluate the function of respiratory complexes I and IV. The results found in the present study revealed that: (a) the mortality rate of the animals submitted to tolerance was 10% when submitted to the lethal dose of LPS, whereas the mortality rate of the control animals was 100% when submitted to the lethal dose of LPS; (B) it was observed that the group receiving controlled doses of LPS and submitted to CLP presented a ratio equal to the control group, suggesting that oxidative phosphorylation remained the same at baseline, whereas the group that underwent CLP procedure without induction of tolerance presented worsening of the respiratory control ratio in relation to the control group; (C) the mitochondrial DNA quantification was higher in the animals submitted to CLP without prior tolerance induction, with an equal increase in mitochondrial biogenesis factors expression in relation to the other groups; (D) there was significant difference in the evaluation of the functionality of complexes I, but no difference in complex IV in all groups. It was concluded that induction of tolerance positively alters mitochondrial function in animals submitted to CLP (AU)

• FAPESP's process: 14/11743-7 - Morphological and functional changes of mitochondria in myocytes and hepatocytes in tolerance to lipopolysaccharide (LPS)
• Grantee: André Augusto Botêga Silva
• Support Opportunities: Scholarships in Brazil - Master