Abstract

G1, G PROTEIN-COUPLED ESTROGEN RECEPTOR, SLOWDOWNS CHRONIC KIDNEY DISEASE DEVELOPMENT IN OVARIECTOMIZED MICE

Hala A. Ahmed*, Mirhan N. Makled, Tarek M. Ibrahim and Ahmed A. Shaaban

ABSTRACT

Cisplatin (CP) is a chemotherapy drug that is known to have a high incidence of nephropathy. Previous studies elucidated that G protein-coupled estrogen receptor (GPER) has a protective effect against renal toxicity. The purpose of this study is to look at the ability of G1, a GPER selective agonist, to slowdown chronic kidney disease (CKD) in ovariectomized (OVX) female mice. Female and OVX-female C57BL/6 mice received two cycles of 2.5 mg/kg CP with a 16-day free period in between (each cycle consists of 5 injections). G1 (50 or 100 μg/kg, i.p.) was given every day for 6 weeks. CP administration caused a significant decrease in body weight, kidney/body weight index, and total antioxidant capacity (TAC) concentration. In addition, CP administration resulted in histopathological changes in female group (p<0.05). Ovariectomy resulted in a more pronounced decrease in body weight, kidney/body weight index, and TAC concentration. In addition to more deterioration of histopathological changes in OVX-CP group
when compared to female-CP group (p<0.05). G1 significantly increased body weight and kidney/body weight index, as well as improving the histopathological alteration compared to the respective CP-treated group (p<0.05). G1 also alleviated the oxidative stress, as evidenced by a dose-dependent increase in TAC concentration. These findings revealed that a female’s sex hormone has a renoprotective effect that could be mediated through GPER. In addition, G1 could be an effective therapeutic technique to slowdown CKD development in both intact females and OVX-mice.

Keywords: G1, Ovariectomy, Chronic kidney disease.