Lipoic acid in experimental sepsis: oxidative stress and mitochondrial function

CIMOLAI, MARÍA CECILIA; VANASCO, VIRGINIA; BOVERIS, ALBERTO; ALVAREZ, SILVIA

Montevideo, Uruguay

Congreso; V Meeting of SFRBM-South American Group; 2007

SFRBM-South American Group

Experimental sepsis occurs with mitochondrial dysfunction and massive increases in nitric oxide production, as part of its pathogenic mechanism. Previous studies showed that oxidative stress is implicated in the tissue damage observed in sepsis, so an antioxidant therapy would be beneficial. Consequently, lipoic acid (an antioxidant with redox properties) was chosen. Sprague-Dowley female rats, 180 g, were injected with 10 mg/kg LPS (lipopolisaccharide) and the assays were carried out after 6 h of treatment. When necessary, lipoic acid (dose: 100 mg/kg) was co-injected with LPS. The study was focused on muscle tissues. A 5.8 fold increase in organ chemiluminescence (CL) was observed for skeletal muscle (control: 7±1 cps/ cm2 ;treated: 41±3 cps/ cm2 ) while liver CL remained unchanged. Oxygen consumption by tissue slices showed a 30-40% increase in heart and diaphragm of septic animals, while the state 3 oxygen uptake in muscle mitochondria was observed to be 40% decreased. NO production was also increased, 90% in diaphragm mitochondria (control: 0.69 ± 0.05 nmol NO/min mg prot) and 30% in heart mitochondria (control: 0.77 ± 0.08 nmol NO/min mg prot). The activity of the mitochondrial complexes I, II and IV, were also measured. Lipoic acid treatment in septic rats: a) decreased skeletal muscle CL; b) returned the mitochondrial NO production to control values. The available data suggest that the oxidative stress and the impairment of mitochondrial function constitute the basis of the molecular mechanism of organ dysfunction in sepsis, that can be partially reverted by lipoic acid.