SCH58261, the antagonist of adenosine A2A receptor, alleviates cadmium-induced preeclampsia via sirtiun-1/hypoxia-inducible factor-1α pathway in rats.

ABSTRACT

OBJECTIVE: To identify the role of adenosine A2A receptor (A2AR) in cadmium-induced preeclampsia (PE) rats and the potential molecular mechanism. PATIENTS AND METHODS: The expression of A2AR in placentae obtained from PE women and normal pregnant (NP) women were measured. The pregnant rats were randomly divided into four groups, including NP rats, PE rats, SCH+NP rats, and SCH+PE rats. The 0.125 mg/kg/d CdCl2 was used to establish a PE rat model in PE and SCH+PE rats. SCH58261 was used as the specific antagonist of A2AR with a concentration of 0.2 mg/kg in SCH+NP and SCH+PE rats. The conditions of mother, foetus, and placenta were tested. The placental expression of A2AR, sirtuin-1 (sirt1), and Hypoxia-Inducible Factor-1α (HIF-1α) was measured by Western blot (WB) and immunohistochemistry (IHC) staining. RESULTS: A2AR and HIF-1α increased, and sirt1 decreased in placenta in both PE women and cadmium-induced PE rats. After treatment with SCH58261, the sirt1 increased and HIF-1a decreased in cadmium-induced PE rats along with the amelioration of maternal outcomes, foetal and placental growth. CONCLUSIONS: This paper firstly revealed that placental A2AR mediated cadmium-induced PE, and A2AR suppression could attenuate placental impairment by acting on the expression of sirt1 and sirt1-mediated regulation of HIF-1α.