Abstract

BARASERTIB ATTENUATES CISPLATIN-INDUCED HEPATOTOXICITY IN MICE

Faisal Alqussair, Mahmoud Elshal, Mirhan N. Makled*, Nashwa Abu-Elsaad

ABSTRACT

Background/Objectives: Cisplatin (CIS) is a widely used chemotherapeutic agent; however, its clinical use is limited by associated hepatotoxicity. The current study aimed at exploring, for the first time, protective potential of barasertib, a selective Aurora kinase B inhibitor, against CIS-induced hepatotoxicity, along with possible underlying mechanisms. Methods: Male mice received cisplatin 20 mg/kg to induce acute liver damage. Barasertib was administered for five consecutive days at two different doses: 20 mg/kg and 40 mg/kg. Results: CIS markedly elevated serum LDH activity, hepatic MDA content, and α-SMA expression (p < 0.001). BAS treatment significantly attenuated all these effects in a dose-dependent manner. BAS at 20 mg/kg reduced LDH activity, lipid peroxidation, and α-SMA immunoreactivity, while the 40 mg/kg dose produced superior protection. Histological analysis confirmed that BAS alleviated hepatocyte damage and suppressed HSC activation, with minimal α-SMA immunoreactivity observed in the CIS+BAS40 group. Conclusions: BAS significantly alleviates CIS-induced hepatotoxicity through antioxidative, cytoprotective, and antifibrotic mechanisms, suggesting it as adjuvant therapy to reduce hepatotoxicity of cisplatin chemotherapy.

Keywords: Aurora kinase; Barasertib; Cisplatin; Hepatotoxicity; Liver fibrosis; Drug repurposing.