Plasmatic levels and tissue distribution of Coenzyme Q10 in intrahepatic cholestasis of pregnancy

MARTINEFSKI M; CONTIN M; RODRIGUEZ, M; BIANCIOTTI, L; LUCANGIOLI S.; TRIPODI V.

Conferencia; The 7th Conference of the International Coenzyme Q10 Association; 2012

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease considered a high risk condition because it may have serious consequences for the fetus such as increased proportion of premature deliveries, fetal distress and perinatal mortality. ICP is characterized by the accumulation of bile acids (BA) in maternal serum which are likely to be responsible of the development of the disease due to their cytotoxic effects. The increased levels of hydrophobic BA are known to induce oxidative stress and apoptosis leading to damage of the liver parenchyma and, eventually, extrahepatic tissues. If this event takes place during gestation, the health of the fetus may be a challenge. Taking into account that Coenzyme Q10 (CoQ10) is an early marker of oxidative stress, in the present study we sought to investigate the plasmatic CoQ10 levels and its relation to cytotoxic BA in normal pregnancy and to those in mothers complicated with ICP. It was found that women with ICP have a significant decrease in plasma CoQ10 levels as compared to normal pregnant woman (0.33±0.03 vs 0.66±0.03µmol/L, mean ±SEM). Furthermore, this CoQ10 reduction was associated to an increase of plasma hydrophobic BA. In order to conclusively demonstrate the presence of CoQ10 deficiency and to identify the most susceptible tissues to oxidative damage in ICP, it was measured CoQ9 and CoQ10 in skeletal muscle, brain, heart and liver together with the plasmatic CoQ levels of rats treated with ethynil estradiol, which is a synthetic estrogen widely used to induce intrahepatic cholestasis in experimental animals. It was observed a decreased CoQ levels in skeletal muscle and brain whilst heart and liver do not seem to be affected. As CoQ is considered the first line of defense in response to an oxidative stress our results indicate that skeletal muscle and brain would be suceptible tissues that would fail to adequately respond to oxidative insult.  We also observed that plasmatic CoQ homologues were diminished in our ICP rat model which is in line with the observed results in humans. The recognition of  CoQ10 deficiency in ICP is important because preventive CoQ10 supplementation may protect against the production of free radicals improving maternal and fetal outcomes.