Fulvestrant alleviates cisplatin-induced acute kidney injury via repression of BNIP3-mediated apoptosis and autophagy

• Published in: Journal of pharmacy and pharmacology 2024-05, Vol.76 (5), p.489-498
• Main Authors: Lee, Hui-Ju, Kim, Yae-Ji, Kim, Kyung-Hyun, Cho, Sung-Pil, Hong, Geum-Lan, Jung, Ju-Young
• Format: Article
• Language: English
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - drug therapy; Acute Kidney Injury - metabolism; Animals; Apoptosis - drug effects; Autophagy - drug effects; Cell Line; Cisplatin - pharmacology; Estrogen Receptor alpha - metabolism; Fulvestrant - pharmacology; Humans; Kidney Tubules, Proximal - drug effects; Kidney Tubules, Proximal - metabolism; Male; Membrane Proteins - metabolism; Mice; Mice, Inbred C57BL; Mitochondrial Proteins; Proto-Oncogene Proteins - metabolism
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1093/jpp/rgad094

Abstract Cisplatin-induced acute kidney injury (AKI) is a clinical disease characterized by a sudden loss of renal function within a few hours or days, due to cisplatin uptake. Fulvestrant is an oestrogen receptor alpha (ERα) antagonist used for endocrine therapy. However, the role of fulvestrant in cisplatin-induced AKI remains unclear. In this study, we investigated the effects of fulvestrant on the regulation of apoptotic cell death and autophagic response in cisplatin-induced AKI. The human kidney proximal tubule epithelial cell line (HK-2) was co-treated with fulvestrant and cisplatin. C57BL/6 mice were subcutaneously injected with fulvestrant and cisplatin was administered via intraperitoneal injection. First, cisplatin treatment increased ERα expression, apoptosis, and autophagy in HK-2 cells. Fulvestrant treatment decreased apoptosis and autophagy, which were accompanied by cisplatin treatment in HK-2 cells. Consistent with in vitro results, cisplatin treatment significantly increased ERα expression in vivo. Additionally, cisplatin treatment increased renal injury, apoptosis, and autophagy. Surprisingly, compared to that in the cisplatin-treated mice group, reduced cisplatin-induced renal injury, apoptosis, and autophagy was observed in the cisplatin+fulvestrant-treated mice group. In summary, these results suggest that fulvestrant plays an important role in cisplatin-induced AKI by decreasing apoptosis and autophagy.