Effects of chronic acetyl-L-carnitine treatment on brain lipid hydroperoxide level and passive avoidance learning in senescence-accelerated mice

In the present study, we examined the effects of acetyl-L-carnitine (ALC) on the brain lipid hydroperoxide level and on passive avoidance performance in senescence-acceleration-prone 8 mice (SAMP8). Mice were treated intraperitoneally with either saline or ALC (100 or 400 mg/kg) three times a week up to 4 months of age (starting at 3 weeks of age). In 4-month-old SAMP8, the deficit in learning and memory seen in saline-treated controls was significantly ameliorated in 400 mg/kg ALC-treated SAMP8, and the brain lipid hydroperoxide level was significantly lower in the 400 mg/kg ALC-treated group than in the saline-treated controls. Administration of 100 mg/kg ALC to SAMP8 did not have significant effect on learning and memory performance or on the brain lipid hydroperoxide level (by comparison with the saline-treated controls). These results suggest that ALC has antioxidant activity towards oxidative stress, and that the improvement in cognitive ability seen with ALC may occur through an amelioration of cellular dysfunction via an inhibition of the increase in lipid hydroperoxidation observed in the brain tissue of untreated SAMP8. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.