Syzygium aromaticum Extract Mitigates Doxorubicin-Induced Hepatotoxicity in Male Rats

Doxorubicin (DOX), an anticancer drug, is used to treat several types of tumors, but it has detrimental side effects that restrict its therapeutic efficacy. One is the iron-dependent form of ferroptosis, which is characterized by elevated ROS production and iron overload. <i>Syzygium aromaticum</i> has a diverse range of biological and pharmaceutical actions due to their antioxidant properties. This study investigated the effect of <i>S. aromaticum</i> extract (SAE) on hepatotoxicity caused by DOX in rats. Phytochemical analysis was performed to assess compounds in SAE. The ADMETlab 2.0 web server was used to predict the pharmacokinetic properties of the most active components of SAE when DOX was injected into rats. Molecular docking studies were performed using AutoDock Vina. Forty male Sprague Dawley rats were divided into four groups of ten rats each (G1 was a negative control group, G2 was given 1/10 of SAE LD₅₀ by oral gavage (340 mg/kg), G3 was given 4 mg/kg of DOX intraperitoneally (i.p.) once a week for a month, and G4 was administered DOX as in G3 and SAE as in G2). After a month, biochemical and histopathological investigations were performed. Rats given SAE had promising levels of phytochemicals, which could significantly ameliorate DOX-induced hepatotoxicity by restoring biochemical alterations, mitigating ferroptosis, and upregulating the NRF-2-SLC7A-11-GPX-4 signaling pathway. These findings suggest that SAE could potentially alleviate DOX-induced hepatotoxicity in rats.