Mitochondrial function and oxidative stress in young, adult, and senescent mice during endotoxemia

CIMOLAI, MARIA CECILIA; VANASCO, VIRGINIA; EVELSON, PABLO; BOVERIS, ALBERTO; ALVAREZ, SILVIA

Sao Pedro

Congreso; VII Meeting of the Society for Free Radical Biology and Medicine – South American Group; 2011

Society for Free Radical Biology and Medicine – South American Group

We have previously shown the importance of O2 metabolism and oxidative pathways in the genesis of tissue injury in endotoxemia. This inflammatory condition and the aging process are characterized by a decreased mitochondrial function due to increased or cumulative production of reactive oxygen and nitrogen species. The aim of this investigation is to study in brain and liver a) oxidative stress by in situ and real-time surface chemiluminescence (CL) and b) mitochondrial mechanisms: O2 consumption pathways; complexes I, II and IV activity, H2O2 and O2- production.  An acute model of endotoxemia was used (10 mg/kg LPS ip) in animals (Swiss male mice) grouped by age (young, adult and senescent) in order to analyze the importance of the aging process in the generated response. Assays were performed after 6 h of treatment. Brain CL was significantly increased when comparing control young (15.6 ± 3 cps/cm2) and senescent (32.6 ± 2 cps/cm2) mice (p<0.001), reflecting the effect of aging. Interestingly, organ CL was mainly affected in the youngest group of animals during endotoxemia, with a 50% and 70% increase in brain and liver respectively. These results correlated with a decreased  complex I activity (control: 79.7 ± 4; LPS: 65.4 ± 3 nmol/min.mg protein) and 20% reduction in state 3 oxygen consumption in brain mitochondria. In conclusion, these results show that the severity and importance of mitochondrial dysfunction and the occurrence of oxidative stress in endotoxemia are age-associated.