The effect of sulodexide on placental mitochondria function in rats with experimental preeclampsia

Abstract

Substitution of drinking water for 1.8% NaCl in pregnant rats caused a pronounced increase in arterial pressure by 24,3% and urinary protein by 117% to day 21 of pregnancy. State 4 respiration of isolated placental mitochondria in the group of negative control was 3- and 1.5-fold higher with malate/glutamate and succinate as substrates than in placental mitochondria isolated from uncomplicated pregnant animals. This led to a decrease of the respiratory control ratio. These results suggest that development of experimental preeclampsia is accompanied by mitochondrial dysfunction through uncoupling of oxidative phosphorylation. Daily administration of sulodexide to females with experimental preeclampsia (EP) per os at a dose of 30 LE during the whole period of gestation decreased manifestations of the disease as evidenced by a slight increase in blood pressure (by 8,6%) and less pronounces increase in urinary protein (by 58,9%). Sulodexide decreased development of mitochondrial dysfunction in EP rats as shown a decrease of non-stimulated ADP respiration with malate/glutamate and succinate (4.5- and 2.5-fold, respectively) as compared with the negative control group and the corresponding increase in the respiratory control ratio (2.5- and 1.5-fold, respectively). Thus, sulodexide reduces uncoupling of oxidative phosphorylation and enhances the functional activity of mitochondria in EP animals, possibly due to its antioxidant and endotelioprotective effects.

Role of Mitochondrial Dysfunction and Reactive Oxygen Species in Mediating Hypertension in the Reduced Uterine Perfusion Pressure Rat Model of Preeclampsia

“…This could be due to inability of these compounds to penetrate mitochondrial membranes to target mitochondrial mediated oxidative stress. Popova et al reported a reduced blood pressure with improved placental mitochondrial function by sulodexide, an anticoagulant drug, in an experimental rat model of preeclampsia (42). Moreover, a few other studies documented the beneficial effect of selenium in preventing mitochondrial oxidative stress in vitro and in vivo models of preeclampsia (43-45).…”

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

“…Increases GAGs synthesis [16] and promotes arterial relaxation [80] There are few reports on effective use during pregnancy [81,82]. Decrease in the PE symptoms (lower blood pressure and less proteinuria) in experimental PE in rats [83].…”

“…Normalization of the total capacity of coagulation and fibrinolytic systems in women with autoimmune hyperthyroidism was noted [81], as well as reduction of complications and improvement of perinatal outcomes in women with fetal loss syndrome on the background of thrombophilia [82]. Administration of sulodexide to rats with experimental PE throughout gestation reduced manifestations of the disease: hypertension, proteinuria, and mitochondrial dysfunction in placenta [83].…”

Is Mitochondrial Oxidative Stress a Viable Therapeutic Target in Preeclampsia?

“…Further, a study by Chen et al documented reduced Complex IV expression and increased oxidative stress markers in the placenta of a HIF-1α-induced PE mouse model [ 48 ]. Furthermore, utilizing a NaCl rat model of PE, Popova et al demonstrated administering 1.8% NaCl to the pregnant rats increases state 4 respiration and reduces respiratory control ratio in the placental isolated mitochondria [ 49 ].…”