ubiquinone and Fetal-Hypoxia

Pregnancy complications associated with prenatal hypoxia lead to increased placental oxidative stress. Previous studies suggest that prenatal hypoxia can reduce mitochondrial respiratory capacity and mitochondrial fusion, which could lead to placental dysfunction and impaired fetal development. We developed a placenta-targeted treatment strategy using a mitochondrial antioxidant, MitoQ, encapsulated into nanoparticles (nMitoQ) to reduce placental oxidative stress and (indirectly) improve fetal outcomes. We hypothesized that, in a rat model of prenatal hypoxia, nMitoQ improves placental mitochondrial function and promotes mitochondrial fusion in both male and female placentae. Pregnant rats were treated with saline or nMitoQ on gestational day (GD) 15 and exposed to normoxia (21% O

Topics: Animals; Antioxidants; Cell Respiration; Female; Fetal Hypoxia; Male; Mitochondria; Mitochondrial Dynamics; Nanoparticles; Organophosphorus Compounds; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Sex Factors; Ubiquinone

Intrauterine growth restriction, a common consequence of prenatal hypoxia, is a leading cause of fetal morbidity and mortality with a significant impact on population health. Hypoxia may increase placental oxidative stress and lead to an abnormal release of placental-derived factors, which are emerging as potential contributors to developmental programming. Nanoparticle-linked drugs are emerging as a novel method to deliver therapeutics targeted to the placenta and avoid risking direct exposure to the fetus. We hypothesize that placental treatment with antioxidant MitoQ loaded onto nanoparticles (nMitoQ) will prevent the development of cardiovascular disease in offspring exposed to prenatal hypoxia. Pregnant rats were intravenously injected with saline or nMitoQ (125 μM) on gestational day (GD) 15 and exposed to either normoxia (21% O

Topics: Age Factors; Animals; Antioxidants; Cardiovascular Diseases; Disease Models, Animal; Female; Fetal Hypoxia; Gestational Age; Hemodynamics; Male; Maternal Exposure; Myocardial Contraction; Nanoparticles; Organophosphorus Compounds; Oxidative Stress; Placenta; Pregnancy; Prenatal Exposure Delayed Effects; Rats, Sprague-Dawley; Sex Factors; Ubiquinone; Ventricular Function, Left

Ischemia and subsequent reperfusion induce lipid peroxidation in the cerebrum of the fetal rat. The present study evaluated the antioxidant activity of endogenous coenzyme Q in protecting against the lipid peroxidation induced in the fetal rat brain by ischemia/reperfusion.. We used wistar rats at day 19 of pregnancy. Fetal ischemia was induced by bilateral occlusion of the utero-ovarian artery for 20 minutes. For reperfusion, the occlusion was released and the circulation was restored for 30 minutes. Control rats underwent sham operation. We determined the levels of thiobarbituric acid-reactive substances, the concentrations of coenzyme Q9, coenzyme Q10, and the mitochondrial respiratory control index in fetal brains.. Occlusion for 20 minutes significantly reduced the respiratory control index (p < 0.01), but did not alter the levels of thiobarbituric acid-reactive substances, coenzyme Q9 or coenzyme Q10. Subsequent reperfusion, however, significantly increased the level of thiobarbituric acid-reactive substances (from 6.53+/-1.54 to 11.46+/-3.31 nM/mg of protein, p < 0.01) and significantly decreased the level of coenzyme Q9 (from 291.73+/-108.94 to 162.44+/-56.83 pM/mg of protein, p < 0.05) and that of coenzyme Q10 (from 153.10+/-75.24 to 79.84+/-30.40 pM/mg of protein, p < 0.05). The respiratory control index was still significantly lower following reperfusion than in controls (p < 0.01). Significant negative correlations were observed between the level of thiobarbituric acid-reactive substances and the concentrations of either coenzyme Q9 (r = -0.68, p < 0.001) or coenzyme Q10 (r = -0.70, p < 0.001).. Endogenous coenzyme Q may protect the fetal rat brain against the lipid peroxidation induced by ischemia/reperfusion.

Topics: Animals; Brain Ischemia; Disease Models, Animal; Female; Fetal Hypoxia; Lipid Peroxidation; Mitochondria; Oxygen Consumption; Pregnancy; Rats; Rats, Wistar; Reperfusion Injury; Thiobarbituric Acid Reactive Substances; Ubiquinone