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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

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

  • Vasilis Spyridon Tseriotis1,2,3
  • Dimitrios Ampazis4,5,6
  • Sofia Karachrysafi7,8
  • Theodora Papamitsou7,8
  • Dimitrios Kouvelas2
  • Konstantinos Stergiou7,8
  • Vasileios Fouskas7,8
  • Pavlos Pavliis2,9
  • Dimitris Hatzibougias10
  • Sofia Chatzianagnosti10
  • Evangelia Dimitra Dimaki10
  • Ioannis Konstantinidis8
8 more authors
  • Dimitrios Tsiptsios11
  • Konstantinos Lallas12
  • Aleksandar Sič13
  • Vasileios Keramidas14
  • Charalampos Tastanis15
  • Kyriaki Papadopoulou8,16
  • Angeliki Cheva17
  • Marianthi Arnaoutoglou18
18 affiliations
  1. 1Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 7HB, UK
  2. 2Laboratory of Clinical Pharmacology, Aristotle University Campus, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  3. 3Department of Neurology, Agios Pavlos General Hospital of Thessaloniki, Leoforos Ethnikis Antistaseos 161, Kalamaria, 55134 Thessaloniki, Greece
  4. 4Department of Respiratory Medicine, Cavan & Monaghan Hospital, H12Y7W1 Lisdarn, Cavan, Ireland
  5. 5School of Medicine, RCSI University of Medicine and Health Sciences, 123 St. Stephen’s Green, D02YN77 Dublin, Ireland
  6. 6School of Physics, Clinical and Optometric Sciences, Clinical Measurement Physiology, Technological University Dublin, Park House Grangegorman, 191 North Circular Road, D07EWV4 Dublin, Ireland
  7. 7Research Team “Histologistas”, Interinstitutional Postgraduate Program “Health and Environmental Factors”, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  8. 8Laboratory of Histology-Embryology, Department of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  9. 9ENT-Clinic, “George Papanikolaou” General Hospital of Thessaloniki, Leoforos Papanikolaou, Exochi, 57010 Thessaloniki, Greece
  10. 10Private Pathology Laboratory “Microdiagnostics”, Mitropoleos 88, 54621 Thessaloniki, Greece
  11. 11Third Department of Neurology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  12. 12Department of Medical Oncology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  13. 13Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
  14. 14Department of Cardiology, Agios Pavlos General Hospital of Thessaloniki, Leoforos Ethnikis Antistaseos 161, Kalamaria, 55134 Thessaloniki, Greece
  15. 15Department of Hygiene, Social & Preventive Medicine and Medical Statistics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  16. 161st Neurosurgery Department, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Kiriakidi 1, 54636 Thessaloniki, Greece
  17. 17Department of Pathology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
  18. 18Laboratory of Clinical Neurophysiology, AHEPA University Hospital of Thessaloniki, Aristotle University of Thessaloniki, Kiriakidi 1, 54636 Thessaloniki, Greece
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{tseriotis2026platinuminduced,
  title = {{Platinum-Induced Toxicity and Zinc-Based Interventions: A Systematic Review of Preclinical Evidence}},
  author = {Vasilis Spyridon Tseriotis and Dimitrios Ampazis and Sofia Karachrysafi and Theodora Papamitsou and Dimitrios Kouvelas and Konstantinos Stergiou and Vasileios Fouskas and Pavlos Pavliis and Dimitris Hatzibougias and Sofia Chatzianagnosti and Evangelia Dimitra Dimaki and Ioannis Konstantinidis and Dimitrios Tsiptsios and Konstantinos Lallas and Aleksandar Sič and Vasileios Keramidas and Charalampos Tastanis and Kyriaki Papadopoulou and Angeliki Cheva and Marianthi Arnaoutoglou},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27219438},
  url = {https://www.mdpi.com/1422-0067/27/21/9438},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Platinum-Induced Toxicity and Zinc-Based Interventions: A Systematic Review of Preclinical Evidence
AU  - Vasilis Spyridon Tseriotis
AU  - Dimitrios Ampazis
AU  - Sofia Karachrysafi
AU  - Theodora Papamitsou
AU  - Dimitrios Kouvelas
AU  - Konstantinos Stergiou
AU  - Vasileios Fouskas
AU  - Pavlos Pavliis
AU  - Dimitris Hatzibougias
AU  - Sofia Chatzianagnosti
AU  - Evangelia Dimitra Dimaki
AU  - Ioannis Konstantinidis
AU  - Dimitrios Tsiptsios
AU  - Konstantinos Lallas
AU  - Aleksandar Sič
AU  - Vasileios Keramidas
AU  - Charalampos Tastanis
AU  - Kyriaki Papadopoulou
AU  - Angeliki Cheva
AU  - Marianthi Arnaoutoglou
PY  - 2026
DA  - 2026/10/23
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27219438
UR  - https://www.mdpi.com/1422-0067/27/21/9438
AB  - 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.
SN  - 1422-0067
ER  -