Is Mitochondrial Oxidative Stress a Viable Therapeutic Target in Preeclampsia?

Abstract

Despite considerable research efforts over the past few decades, the pathology of preeclampsia (PE) remains poorly understood with no new FDA-approved treatments. There is a substantial amount of work being conducted by investigators around the world to identify targets to develop therapies for PE. Oxidative stress has been identified as one of the crucial players in pathogenesis of PE and has garnered a great deal of attention by several research groups including ours. While antioxidants have shown therapeutic benefit in preclinical models of PE, the clinical trials evaluating antioxidants (vitamin E and vitamin C) were found to be disappointing. Although the idea behind contribution of mitochondrial oxidative stress in PE is not new, recent years have seen an enormous interest in exploring mitochondrial oxidative stress as an important pathological mediator in PE. We and others using animals, cell models, and preeclamptic patient samples have shown the evidence for placental, renal, and endothelial cell mitochondrial oxidative stress, and its significance in PE. These studies offer promising results; however, the important and relevant question is can we translate these results into clinical efficacy in treating PE. Hence, the purpose of this review is to review the existing literature and offer our insights on the potential of mitochondrial antioxidants in treating PE.

Eucommia granules activate Wnt/β-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats

“…Eucommia granules activate Wnt/β-catenin pathway, and improve oxidative stress, inflammation, and endothelial injury in preeclampsia rats Although the etiology of PE is still controversial, it is generally accepted that hypoxia and oxidative stress caused by placental insufficiency play an important role in the development of the disease 22 . The literature suggests that suppression of oxidative stress is effective in reducing the incidence of PE in high-risk pregnant women 23 .…”

Pathomechanisms of Prenatally Programmed Adult Diseases

“…In addition, the anti-angiogenic factor sFlt-1, generated by the activation of AT1R, has also been claimed to stimulate placental and endothelial mtROS. However, this effect can be abrogated by the progesterone-induced blocking factor [161].…”

Endothelial dysfunction in preterm infants: The hidden legacy of uteroplacental pathologies

“…In this direction, studies indicate that using a ROStargeted therapy with antioxidants may be a promising approach in perinatal medicine, especially for fetal neuroprotection (196). However, many proposed drugs are still under investigation for routine clinical use, such as vitamins, melatonin, lycopene, selenium, acetylsalicylic acid, L-ergothioneine, and mitochondria-specific drugs (197)(198)(199)(200)(201)(202)(203)(204)(205)(206)(207)(208)(209)(210).…”