Impact of zinc supplementation on cellular and molecular biomechanical alterations and critical outcomes in pediatric patients with sepsis: A randomized controlled trial

  • Idham Jaya Ganda Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia; Dr. Wahidin Sudirohusodo Hospital, Makassar 90245, Indonesia
  • Aldora Jesslyn Oentari Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia
  • Ninny Meutia Pelupessy Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia; Dr. Wahidin Sudirohusodo Hospital, Makassar 90245, Indonesia
  • Amiruddin Laompo Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia; Dr. Wahidin Sudirohusodo Hospital, Makassar 90245, Indonesia
  • Setia Budi Salekede Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia; Dr. Wahidin Sudirohusodo Hospital, Makassar 90245, Indonesia
  • Syarifuddin Rauf Department of Pediatrics, Faculty of Medicine, Hasanuddin University, Makassar 90245, Indonesia
DOI: https://doi.org/10.62617/mcb418
Keywords: zinc supplementation; ARDS; AKI; shock; sepsis; biomechanical responses; children
Article ID: 418

Abstract

Background: Sepsis remains a significant contributor to illness and death in children. Studies suggests that potential benefits of zinc supplementation in patients with sepsis, such as reduced inflammation and mortality rates. Zinc is involved in maintaining the structural integrity and function of cell membranes, which is essential for proper cell signaling and biomechanical responses. It can also influence the activity of key enzymes and proteins that regulate intracellular and extracellular forces, thereby affecting cell adhesion, migration, and overall tissue mechanics. Therefore, this study aimed to evaluate the occurrence of Acute Respiratory Distress Syndrome (ARDS), Septic Shock, Acute Kidney Injury (AKI), and Mortality in Pediatric Sepsis receiving Zinc supplementation, with a focus on the underlying cellular and molecular biomechanical mechanisms. Methods: This study was a Randomized Control Trial (RCT) conducted using a parallel-group, double-blind design and prospective cohort approach. Participants were selected through consecutive sampling and then randomized into two groups: one receiving standard therapy plus zinc supplementation and the other receiving standard therapy plus a placebo. Results: Among pediatric patients with sepsis, the incidence of septic shock was significantly lower in the group receiving standard therapy with zinc supplementation (34.4%) compared to the placebo group (65.6%) (p = 0.00, OR 2.29, 95% CI: 1.28–4.11). The incidence of ARDS was 66.7% in the placebo group, versus 33.3% in the zinc group (p = 0.00, OR 0.37, 95% CI: 0.22–0.64). For acute kidney injury (AKI), 65.7% occurred in the placebo group compared to 34.3% in the zinc group (p = 0.04, OR 2.09, 95% CI: 0.99–4.40). Mortality in the placebo group was 64.3%, while in the zinc group it was 35.7% (p = 0.01, OR 0.48, 95% CI: 0.26–0.88). Conclusion: Zinc supplementation significantly reduces the incidence of acute respiratory distress syndrome, acute kidney injury, septic shock, and mortality in pediatric patients with sepsis. These outcomes may be attributed to zinc’s role in modulating cellular signaling pathways, enhancing cellular integrity under stress, and improving the biomechanical properties of cell membranes, thereby promoting better physiological responses in the context of sepsis.

References

1. Yuniar I, Karyanti MR, Kurniati N, et al. The clinical and biomarker approach to predict sepsis mortality in pediatric patients. Paediatrica Indonesiana (Paediatrica Indonesiana). 2023; 63(1): 37–44.

2. Kawasaki T. Update on pediatric sepsis: a review. J Intensive Care. 2017; 5: 47.

3. Schlapbach LJ. Paediatric sepsis. Curr Opin Infect Dis. 2019; 32(5): 497–504.

4. Winny, Lubis M, Mutiara E. Effect of zinc supplementation in pelod-2 score and zinc serum level in children with sepsis. Crit Care Shock. 2021;24(2): 80–4.

5. Celik IH, Hanna M, Canpolat FE, et al. Diagnosis of neonatal sepsis: the past, present and future. Pediatr Res. 2022 Jan; 91(2): 337–50.

6. Haque IU, Udassi JP. Current Trends in Pediatric ARDS. Vol. 2019, Qatar Medical Journal. 2019.

7. Shen KL, Yang YH, Jiang RM, et al. Updated diagnosis, treatment and prevention of COVID-19 in children: experts’ consensus statement (condensed version of the second edition). World J Pediatr. 2020; 16(3): 232–9.

8. Besecker BY, Exline MC, Hollyfield J, et al. A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission. Am J Clin Nutr. 2011; 93(6): 1356–64.

9. Prasertsan P, Anantasit N, Walanchapruk S, Roekworachai K, Samransamruajkit R, Vaewpanich J. Sepsis-related pediatric acute respiratory distress syndrome: A multicenter prospective cohort study. Turk J Emerg Med. 2023; 23(2): 96–103.

10. Xia W, Li C, Zhao D, et al. The Impact of Zinc Supplementation on Critically Ill Patients with Acute Kidney Injury: A Propensity Score Matching Analysis. Front Nutr. 2022; 9(6): 1–8.

11. Kim M, Maruhashi T, Asari Y. Effectiveness of Zinc Supplementation for Sepsis Treatment: A Single-Center Retrospective Observational Study. Nutrients. 2024;16(17).

12. Nowak JE, Harmon K, Caldwell CC, et al. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr Crit Care Med. 2012; 13(5): e323-9.

13. Tang Z, Wei Z, Wen F, et al. Efficacy of zinc supplementation for neonatal sepsis: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2019; 32(7): 1213–8.

14. Newton B, Bhat BV, Dhas BB, et al. Effect of Zinc Supplementation on Early Outcome of Neonatal Sepsis--A Randomized Controlled Trial. Indian J Pediatr. 2016; 83(4): 289–93.

15. Chen B, Yu P, Chan WN, et al. Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets. Sig Transduct Target Ther 9. 2024. doi: 10.1038/s41392-023-01679-y

16. Hristov BD. The Role of Glutathione Metabolism in Chronic Illness Development and Its Potential Use as a Novel Therapeutic Target. Cureus. 2022; 14(9): e29696. doi: 10.7759/cureus.29696

17. Ho E, Wong CP, King JC. Impact of zinc on DNA integrity and age-related inflammation. Free Radical Biology and Medicine. 2022; 178: 391-397. doi: 10.1016/j.freeradbiomed.2021.12.256

18. Hernández-Camacho JD, Vicente-García C, Parsons DS, Navas-Enamorado I. Zinc at the crossroads of exercise and proteostasis. Redox Biol. 2020; 35: 101529.

19. Alker W, Haase H. Zinc and Sepsis. Nutrients. 2018; 10(8): 976. doi: 10.3390/nu10080976

Published
2025-01-15
How to Cite
Ganda, I. J., Oentari, A. J., Pelupessy, N. M., Laompo, A., Salekede, S. B., & Rauf, S. (2025). Impact of zinc supplementation on cellular and molecular biomechanical alterations and critical outcomes in pediatric patients with sepsis: A randomized controlled trial. Molecular & Cellular Biomechanics, 22(1), 418. https://doi.org/10.62617/mcb418
Issue
Vol. 22 No. 1 (2025)
Section
Article

Copyright (c) 2025 Idham Jaya Ganda, Aldora Jesslyn Oentari, Ninny Meutia Pelupessy, Amiruddin Laompo, Setia Budi Salekede, Syarifuddin Rauf

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright on all articles published in this journal is retained by the author(s), while the author(s) grant the publisher as the original publisher to publish the article.

Articles published in this journal are licensed under a Creative Commons Attribution 4.0 International, which means they can be shared, adapted and distributed provided that the original published version is cited.