Platinum-Induced Toxicity and Zinc-Based Interventions: A Systematic Review of Preclinical Evidence

Zinc may mitigate platinum-induced toxicity through antioxidant, anti-inflammatory and anti-apoptotic effects. We systematically reviewed preclinical in vivo evidence on zinc-based interventions, focusing on organ protection, mechanisms and antitumour efficacy. PubMed, Scopus, Web of Science and supplementary sources were searched for studies in rats and mice. Risk of bias was assessed using SYRCLE, and the findings were synthesised narratively. Database searches identified 1552 records; 25 studies were included following database and supplementary screening. The risk of bias was frequently unclear for sequence generation, allocation concealment and blinding. Most studies investigated cisplatin; fewer evaluated carboplatin, oxaliplatin or combination chemotherapy. Zinc interventions included salts, dietary supplementation, organic complexes and nanoformulations, predominantly administered before platinum exposure. Protective findings were reported across renal, reproductive, nervous, hepatic, haematopoietic and cardiovascular systems. Proposed mechanisms included metallothionein induction, enhanced antioxidant defences and modulation of inflammation and apoptosis. Heterogeneity precluded conclusions about formulation superiority. Limited tumour-bearing evidence indicated that zinc-induced metallothionein may reduce cisplatin activity, whereas bismuth zinc citrate preserved tumour control within the tested model. Methodological weaknesses, heterogeneity and scarce tumour-bearing evidence limit confidence in efficacy and oncological safety. These findings support further preclinical investigation rather than clinical implementation.