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

This systematic review of 81 preclinical animal studies on cytarabine (Ara-C) highlights its dose- and regimen-dependent toxicities affecting multiple organs, with neurotoxicity being the most common, followed by intestinal mucositis, ocular injury, alopecia, hepatotoxicity, nephrotoxicity, and developmental anomalies. The toxicities are linked to oxidative stress, inflammatory cascades, apoptosis, and epigenetic dysregulation. However, the study quality was moderate, with issues in randomization, blinding, and sample-size justification, which raises concerns about reproducibility. Despite the clinical relevance, cardiotoxicity was not evaluated in these studies. The review concludes that while animal studies offer mechanistic insights, their predictive value is limited by methodological weaknesses and translational gaps, necessitating more rigorous research designs and molecular profiling to identify biomarkers and protective strategies.