<i>Annona squamosa</i> (custard apple) leaves extract mitigates abemaciclib-induced liver injury (AILI) in male rats

Abemaciclib-induced liver injury (AILI) is a significant concern in clinical practice, since it may need dose reduction or withdrawal of abemaciclib and might impact following therapy options. Annona squamosa is a medicinal plant that produces edible fruits, usually referred to as the sugar apple. This plant is a member of the Annonaceae family and has been utilized as a traditional remedy for many years, offering advantages for individuals with diverse ailments. This study aims to assess the hepatotoxic effects of abemaciclib on male rats and the potential mitigative role of Annona squamosa leaf extract (ALE) against these effects. This study utilized forty male albino rats. The rats were categorized into four groups (ten per group): the control group, the ALE-supplemented group (150 mg/kg/day), the abemaciclib-administered group (13 mg/kg/day), and the group receiving co-administration of abemaciclib and ALE. The experiment was prolonged for eight weeks. Abemaciclib-administered rats exhibited decreased body weight, increased liver weight and relative body weight, hepatic dysfunction, oxidative stress, and inflammation, as well as detrimental histological alterations in liver tissues. Co-administration of ALE with abemaciclib significantly improved liver functions, including ALT, AST, and total bilirubin, as well as fibrotic indices such as hyaluronic acid and laminin. ALE effectively mitigated oxidative stress and inflammation in liver tissues induced by abemaciclib, evidenced by significant enhancements in liver antioxidant enzymes such as SOD, CAT, and GSH-GPx, as well as reductions in pro-inflammatory markers like IL-1β, IFN-γ, and iNOS. Also, ALE mitigated the deleterious histological manifestations of liver, including cellular infiltration, pyknosis, and fibrosis, caused by abemaciclib. Annona squamosa leaves extract has a powerful mitigative efficacy against abemaciclib-induced liver oxidative stress, inflammation, and histopathological changes.