Cisplatin, also known as Cis-diamminedichloroplatinum II, is a widely used chemotherapeutic agent in clinical practice. It is highly effective in treating various solid tumours, including ovarian, testicular, prostate, bladder, head and neck, and lung cancers (Dasari and Bernard Tchounwou, 2014). This antineoplastic agent, based on platinum, is highly effective against various malignancies, including ovarian, testicular, prostate, bladder, head and neck, and lung cancers (Scherpereel et al., 2018). However, cisplatin is effective in killing cancer cells, but it is also toxic to normal cells of multi-organisation. Its severe nephrotoxicity and hepatotoxicity are the most notable side effects, which limit its use in the clinical setting (Dugbartey et al., 2016; Qi et al., 2019). In clinical practice, cisplatin-induced acute liver injury (ALI) may occur when cisplatin has been administered at high doses, thus becoming a barrier to its continued use (El Nashar et al., 2021; Hoofnagle and Björnsson, 2019; Mansour et al., 2006). Cisplatin has been found to accumulate in the liver over a long period of time, and the damage it causes to the liver may result in ultrastructural changes in liver tissue, leading to the death of hepatocytes (Ge et al., 2023; X. Zhu et al., 2022). Besides, the liver and kidney have mutual influence on each other, and the hepatotoxicity of cisplatin has been reported to aggravate the nephrotoxicity (Galfetti et al., 2020; Kim et al., 2018). Indeed, hepatic failure remains the most serious clinical consequence of the drugs used in the practice. Adverse drug reactions affecting hepatic function and concomitant liver injury will be a non-negligible challenge for the present and future use of cisplatin.

The exact mechanism by which cisplatin induces acute liver injury is not fully understood, but it is now suggested to be related to programmed cell death (PCD) (Shin et al., 2005). Ferroptosis is a newly identified PCD, and it is commonly established that ferroptosis is the important type of PCD that occurs in cisplatin-induced acute kidney injury (Dixon et al., 2012; Hu et al., 2020; Kim et al., 2022; Xie et al., 2023; Yang and Stockwell, 2016). During the writing of this article, it was also confirmed that ferroptosis acts an important role in cisplatin-induced acute liver injury (Guo et al., 2023). Cisplatin is hydrolysed to an active form capable of cross-linking with purine bases on DNA, followed by DNA damage leading to the accumulation of reactive oxygen species (ROS) and lipid peroxidation (Maekawa et al., 2019; Trimmer and Essigmann, 1999). There is also binding of cisplatin to mitochondrial DNA (mtDNA) leading to mtDNA damage and then mitochondrial dysfunction, which results in the overproduction of ROS (Shu et al., 2016). Besides, Cisplatin treatment induces serum iron accumulation (Guo et al., 2023). All of these cisplatin-induced abnormalities in cellular function are the breeding ground for ferroptosis. Hence, inhibiting ferroptosis represents a promising treatment approach against cisplatin-induced acute liver injury.

Of note, the use of hydration or other anti-symptomatic treatments to attenuate the potential histotoxicity of cisplatin is commonly used in the clinical practice, but its effectiveness is limited. Thus, the feasibility of new treatments to attenuate cisplatin-induced acute liver injury needs to be further explored to improve clinical outcomes in oncology patients. Thousands of years clinical experience have been accumulated by traditional Chinese medicine (TCM) in the treatment of acute liver injury. Increasing interest has been aroused in recent years in a variety of small molecule compounds extracted from TCM. Astragalus membranaceus (Huang qi) is a traditional Chinese medicine and food which has been used for many years to tonify liver functions (Auyeung et al., 2016). Astragaloside IV (ASIV), one of the representative active constituents of Astragalus membranaceus (Fisch.) root, has been identified as one of the key compounds with multiple pharmacological effects in the treatment of acute liver injury caused by multiple factors (Ren et al., 2013). As a quality control marker for Astragalus membranaceus, some studies have found the role of astragaloside IV in ameliorating cisplatin-induced organ damage, with the main focus of attention on the kidney (Yan et al., 2017). Meanwhile, astragaloside IV has been consensus as a sensitiser that can make improvements in cisplatin resistance in several types of tumours (Qu et al., 2020; Xie et al., 2016). On the other hand, there are a few studies suggesting that astragaloside IV possesses the ability to fight ferroptosis (Wang et al., 2023). However, the role and potential action mechanisms of astragaloside IV in the treatment of cisplatin-induced acute liver injury have not been systematically addressed, and the binding mechanism and interaction mode between astragaloside IV and ferroptosis are unknown. We speculated that astragaloside IV could prevent the progression of cisplatin-induced acute liver injury through different mechanisms via ferroptosis-dependent pathway.