Quercetin, coenzyme Q10 and L-canavanine as protective agents against lipid peroxidation and nitric oxide generation in endotoxin-induced shock in rat brain

The present study was designed to evaluate the possible protective effect of quercetin, coenzyme Q(10) (CoQ(10)), or L-canavanine treatments against endotoxin-induced shock in rat brain. Shock was induced by i.p. injection of 10 mg kg(-1) of lipopolysaccharide (LPS) and was biochemically manifested 2 h after injection as an increase in brain malondialdehyde (MDA), total nitrite/nitrate (NOx), glutathione peroxidase (GSHPx), and blood lactate level/activity. On the other hand, endotoxemia resulted in reduced brain glutathione (GSH) and phospholipids' content as well as the serum sulfhydryl groups' (SH-group) value. Pretreatment with quercetin (200 mg kg(-1) per os) 2 h before LPS injection diminished the shock-induced increases in brain MDA, and NOx levels while elevating the reduced brain phospholipids' and serum SH groups' content. CoQ(10) administered at a dose of 200 mg kg(-1) per os for 7 days prior to shock induction, reduced the elevated levels of brain MDA, NOx, and GSHPx level/activity due to redundancy. The same treatment caused a 3-fold increase in the reduced brain GSH level and normalized the depressed phospholipids' content. Treatment of animals with L-canavanine (50 mg kg(-1) i.p.) simultaneously with LPS injection, reduced the elevated level of blood lactate. Brain superoxide dismutase (SOD) level was neither affected by endotoxin nor by different treatments. In conclusion, this study indicates that SOD may not reflect the level of peroxidation and points to the value of quercetin, CoQ(10), and L-canavanine in ameliorating the oxidative status of brain during the early phase of endotoxic shock. (C) 2001 Academic Press.