Lactoferrin and zinc sulfate supplementation alleviate cisplatin-induced taste disorder: underlying mechanisms via taste and immune modulation

Abstract Taste disorder is a common chemotherapy-associated consequence that markedly suppresses the appetite of patients and impacts their quality of life. This study investigated the mechanisms of dietary supplementation of lactoferrin (LF), alone or combined with ZnSO₄, in alleviating cisplatin-induced metallic taste disorder using a mouse model. Two-bottle preference (TBP) test demonstrated that both LF and LF+ZnSO₄ supplementation significantly decreased the metallic taste preference ratio from 82.5 ± 9.4% to 24 ± 5.4% and 20 ± 4.0%, respectively. Transcriptomic analysis revealed that LF upregulated ( P < 0.05) genes associated with metallic taste receptor, signal transduction, and immune responses, while downregulating genes associated with Fe 2+ -induced lipid oxidation pathway, which might contribute to taste recovery and mucosal defense. ZnSO₄ in combination with LF further elevated the expression of genes involved in metallic taste signaling and intracellular mediators. Co-application of LF and ZnSO₄ was associated with additional changes in the expression of immune-related genes in the oral epithelium; however, this transcriptional difference was not accompanied by a further improvement in taste behavior. The results of this study highlight LF and ZnSO₄ supplementation as promising dietary strategies to alleviate chemotherapy-induced metallic taste disorder and shed light on the underlying mechanisms.