Hexarelin alleviates apoptosis on ischemic acute kidney injury via MDM2/p53 pathway.

Preclinical study using in vivo rat models and in vitro cell lines to investigate the protective effects of Hexarelin on ischemia/reperfusion-induced acute kidney injury.

“In this study, we investigated the therapeutic potential of Hexarelin in I/R-induced AKI and elucidated its molecular mechanisms.”

Healthy male Sprague-Dawley rats and human renal proximal tubular epithelial cells (HK-2).

“Healthy male SPF SD rats (Jinan Pengyue Animal Centre) aged 8 weeks weighing 250–300 g were obtained from Jinan Pengyue Animal Centre.”

Fifty rats divided into five groups of ten each; HK-2 cell experiments involved multiple concentrations and time points.

“A total of fifty rats were randomly assigned to 5 groups (n = 10), normal, sham, AKI, Hexarelin-AKI, and Saline-AKI.”

Rats were pretreated for 7 days prior to ischemia/reperfusion injury, with sacrifice occurring 24 hours post-injury.

“In the I/R-induced AKI model, rats were pretreated with Hexarelin at 100 μg/kg/d for 7 days before being sacrificed 24 h post-IRI.”

Hexarelin pretreatment mitigated post-ischemic kidney pathological changes, improved renal function markers, and inhibited apoptosis in rats.

“However, pretreatment with Hexarelin exhibited a protective effect by mitigating post-ischemic kidney pathological changes, improving renal function, and inhibiting apoptosis.”

Hexarelin reduced cell apoptosis in HK-2 cells exposed to hypoxia/reoxygenation by downregulating pro-apoptotic genes and upregulating anti-apoptotic proteins.

“Consistent with the in vivo results, Hexarelin also reduced cell apoptosis in post-H/R HK-2 cells.”

Molecular docking and expression analysis indicated that Hexarelin interacts with MDM2, leading to the suppression of MDM2 and p53 expression.

“Molecular docking revealed a strong binding affinity between Hexarelin and MDM2, suggesting the potential mechanism of Hexarelin’s anti-apoptosis effect at least partially through its interaction with MDM2, a well-known negative regulator of apoptosis-related protein that of p53.”

The study relies on animal and cell models, and the authors note that further research is needed to gather additional evidence regarding the therapeutic use of Hexarelin.

“Nevertheless, further research is needed to gather additional evidence.”