Hydroxychloroquine improves manifestation of PE rats under oxidative stress by regulating the PI3K/AKT/mTOR signaling pathway to inhibit autophagy

Abstract

Preeclampsia is the leading cause of maternal and fetal morbidity and mortality worldwide. Oxidative stress involved in the development of preeclampsia. Hydroxychloroquine, an antimalarial drug, has a variety of drug properties, one of which is the antioxidant effect. In this study, we established an in vitro cellular oxidative stress model and a preeclampsia rat model with the aim of investigating the effects of hydroxychloroquine on oxidative stress injury and its associated mechanisms. Our study showed that hydroxychloroquine lowered blood pressure and urinary protein, ameliorated placental and renal damage, and improved preeclampsia rat outcomes. Hydroxychloroquine treatment reactivated the PI3K-AKT-mTOR pathway and inhibited excessive autophagy to ameliorate oxidative stress injury, and these effects were attenuated after application of the PI3K inhibitor LY294002. In summary, hydroxychloroquine may inhibit autophagy by activating the PI3K-AKT-mTOR pathway, which in turn ameliorates oxidative stress injury and improves preeclampsia outcomes. Our study provides a new theoretical basis for hydroxychloroquine application for preeclampsia therapy.