The Action of Acetyl‐l‐Carnitine on the Neurotoxicity Evoked by Amyloid Fragments and Peroxide on Primary Rat Cortical Neurones

Abstract

The amyloid β‐peptides have been implicated in the excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. In this paper we examine the effect of different amyloid fragments (β A1–40, A1–28, and A25–35), as well as potential neuroprotective compounds on rat cortical neuron viability. Exposure of neurones to β A25–35 or A1–40 at concentrations as low as 1 μg/ml inhibited, significantly, the MTT response and this level of inhibition was similar after 24‐h or three‐day exposure. Furthermore, the level of inhibition was not affected by the presence or absence of 5% horse serum in the medium. Preexposure (10 min) of neurones to ALC at concentrations of 0.1, 1, 5, and 10 mM attenuated the inhibition of the MTT response caused by β A25–35 (50 μg/ml) in serum free medium for 24 h. The treatment of cells with vitamin E (100 μM), catalase (4 mg/ml), NGF (0.1 and 10 ng/ml), or cycloheximide (0.1 μg/ml) significantly restored the MTT response that was inhibited by β A25–35. The mechanism for the protective actions of these compounds against β A25–35 toxicity is not clear but may involve free radical scavenger action and preservation of energy production, although other mechanisms, especially for ALC, such as a direct effect on A‐β interaction with charged anionic phospholipids and/or stabilizing action on membranes, are also possible.

Neuroprotection by Acetyl-<i>L</i>-Carnitine after Traumatic Injury to the Immature Rat Brain

“…Once inside the mitochondrial matrix, ALCAR is converted to acetyl CoA and free carnitine via carnitine acyl transferases [24]. Numerous reports show neuroprotective effects of exogenous ALCAR in a number of neurologic disorders [22,25,26,27,28,29,30]. Supraphysiologic levels of exogenously administered ALCAR provide neuroprotection in animal models of neurodegenerative diseases and acute neurologic injury paradigms [22,23,24,31].…”

Acetyl-L-carnitine prevents total body hydroxyl free radical and uric acid production induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the rat

“…S radical production by MPTP Unlike salicylic acid (Kuhn et al, 1995), ALCAR is not known to have any scavenging effect on HO S radical (Virmani et al, 2001). Thus its ability to prevent the production of HO S radicals must lie at another level.…”

Improvement of Visual Functions and Fundus Alterations in Early Age-Related Macular Degeneration Treated with a Combination of Acetyl-<i>L</i>-Carnitine, n-3 Fatty Acids, and Coenzyme Q10

“…Previous studies in heart and brain showed that dietary supplementation with a blend of n-3 FA and carnitine/ALC was associated with (a) extensive changes in the activities of key enzymes in the mitochondria [33], (b) improved recovery of mitochondrial energy metabolism [57], (c) increased n-3 FA content of mitochondrial membranes [58], and subsequent improvement in mitochondrial Ca 2+ flux and Ca 2+ -dependent processes [34], as well as (d) improvement of lipid metabolism [59, 60]. Taking these findings together with our findings we assume that beneficial effects of Phototrop on visual functions in early AMD may come from the synergetic action of ALC, n-3 FA, and CoQ10 on mitochondrial functions.…”