The effect of exogenous coenzyme Q10 on its distribution and its role as protective agent against DNA damage

Abstract

Coenzyme Q10 (Q10) acts as an important in vivo anti-oxidant and has been widely advocated to be a beneficial dietary adjuvant because elevated concentrations of Q10 should effect a higher energy production and anti-oxidant capacity, leading to lower DNA damage and cell death. It remains controversial however, whether oral administration of Q10 can significantly enhance its tissue levels and/or can modulate the level of oxidative stress (DNA damage) in vivo. We investigated whether oral administration of coenzyme Q10 (Q10) in mice could increase the levels of its reduced form, Q10H2, in blood and in tissue (brain, liver and heart) and determined the relationship between Q10H2 concentrations in the blood and various tissues. These concentrations were correlated with cell DNA damage found in blood and in brain, liver and heart tissue. We also investigated if oral administration of Q10 could attenuate the neurotoxicity of 1- methyl-4-phenyl-1,2,3,64 etrahydropyridine (MPTP) in old mice, using damage to cell DNA as the parameter. In this study a method for assessing chemically and environmentally induced cell DNA damage was developed, using the single cell gel electrophoresis (SCGE) assay and compared these results with coenzyme Q concentrations in various tissue samples obtained by using a validated HPLC analysis with electrochemical detection. Four groups of one-year-old C57BL/6 mice received a standard diet or a diet supplemented with Q10 (200mg/kg/day) for six weeks. After four weeks, one group that had received the standard diet and one group that had received the Q10 supplemented diet were treated additionally with one dosage of MPTP (40mg/kg). The results showed that the Q10H2 as well as the Q9H2 concentrations were elevated in the plasma, brain, heart and liver of those groups receiving Q10 and Q10 + MPTP. This observation, as well as the phenomenon that the Q9H2 levels were higher than the Q10H2 levels in the controls indicated that Q9 is the predominant Q homologue in mice and that oral intake of Q10 increased the levels of both Q9H2 and Q10H2 in tissue and blood. The heart, brain and liver cells exhibited significantly higher DNA damage in the groups treated with MPTP. The group receiving MPTP plus Q10 displayed less DNA damage than the MPTP group indicating that Q10 most likely act as an ameliorating factor for MPTP neurotoxicity. The blood samples before and after treatment in contrast, showed very little difference in DNA damage. This might be explained by the fact that blood cells regenerate much faster than other tissue. Our findings indicate that levels of Q10 and Q9 can be increased in tissue by long-term supplementation with Q10 and that Q10 could attenuate/prevent DNA damage in various cells. This suggests that Q10 may be useful in disorders where there is impaired activity of complex I, which might lead to DNA damage of the cell, such as Parkinson's disease.