Carnitine prevents clastogenic effects induced by hydrogen peroxide in mammalian cells

Carnitine is a small essential molecule that regulates the substrate flux and energy balance across cell membranes by modulating both the transport of long-chain fatty acids into mitochondria and their subsequent β-oxidation. Although humans are capable to synthesize it endogenously, approximately 75% of body carnitine sources come from diet and particularly from food of animal origin such as meat, poultry, fish and dairy products. Due to its intrinsic interaction with the bioenergetics processes, carnitine plays an important role in diseases associated with metabolic compromise, especially mitochondria-related disorders. It has been reported that administration of carnitine by diet or at pharmacological doses can have significant benefit in several physiopathological situations such as ischemia, myocardial injury and neurodegenerative diseases, but there is no data on the possible protective role of carnitine against other oxidative stress-induced pathologies associated with an altered chromosome stability such as cancer. Therefore, we analysed the potential capability of carnitine to protect mammalian cells from genetic instability induced by H2O2, using Chinese Hamster Ovary (CHO) cells as a mammalian cell model having a stable karyotype and the chromosome aberration test as genetic end point. Our results showed that in the absence of carnitine H2O2 induced a high and dose-depend-ent induction of structural chromosome aberrations in the concentration range 0.1-0.4 mM whereas at the same H2O2 doses, a pre-treatment with 4 mM carnitine produced a strong decrease either of the percent of cells with aberrations or of the aberration frequency. The observed carnitine-mediated prevention of H2O2-induced chromosome aberrations reaches almost the control value in the cultures treated with 0.1 mM of H2O2 thus evidencing a reduction of about 70%. These data, together with preliminary results showing that carnitine is not able to protect cells from the inhibition of cell growth caused by H2O2, suggest that carnitine protects mammalian cells from H2O2–induced clastogenic damage and this effect is reproducible and highly specific.