Unraveling Translational Insights Into Systemic Multi-Organ Toxicity of Cytosine Arabinoside (Ara-C): A Systematic Review of Preclinical Animal Evidence

This systematic review synthesizes data from 81 preclinical animal studies to examine the systemic multi-organ toxicity of cytarabine (Ara-C). The review identifies neurotoxicity as the most frequently reported adverse effect, followed by intestinal mucositis, ocular injury, alopecia, hepatotoxicity, nephrotoxicity, and developmental anomalies. The toxicities are dose-dependent and linked to mechanisms such as oxidative stress, inflammation, apoptosis, and epigenetic dysregulation. Despite providing valuable insights, the studies often lack methodological rigor, limiting their clinical applicability. The review calls for more robust study designs and comprehensive assessments to improve translational relevance and suggests exploring biomarkers and protective strategies to mitigate Ara-C's adverse effects.