PROTECTIVE ACTIONS OF L-CARNITINE AND ACETYL-L-CARNITINE ON THE NEUROTOXICITY EVOKED BY MITOCHONDRIAL UNCOUPLING OR INHIBITORS

The mechanism for the pathological increase in cell death in various d isease states e.g. HIV immunodefficiency or even ageing err Alzheimer' s disease, occurs by complex and as yet undefined mechanism(s) related to immunological, virological or biochemical disturbances (i.e, energ y depletion, oxidative stress, increased protein degradation). We have studied mitochondrial uncoupling or inhibitor toxicity on neurones at the cellular level and at the mitochondrial level using rhodamine (Rh 123) and 10-nonylacridine orange (NAG) fluorescence with confocal micr oscopy. Blockade of the mitochondrial chain complexes at various point s was studied. The possible protective effects of the compound L-carni tine, which plays a central role in mitochondrial function, was tested in this form of neurotoxicity. It appears that L-carnitine and its ac etylated form, acetyl-L-carnitine, can attenuate the cell damage, as a ssessed by lactate dehydrogenase (LDH) release, evoked by the uncouple r, p-(trifluoromethoxy)phenylhdyrazone (FCCP), or by the inhibitors, 3 -nitropropionic acid (3-NPA) or rotenone. Further, the FCCP-induced in hibition of Rh 123 uptake was antagonized by the preincubation of cell s with L-carnitine. Since such neurotoxic mechanisms may be operating in the various pathological forms of myotoxicity and neurotoxicity, th ese observations suggest potential for a therapeutic approach. (C) 199 5 The Italian Pharmacological Society.