Zinc as therapeutic agent in skin and wound care has been known for centuries, but its role is controversial and comprehensive investigations in nutrient-deficient environments are lacking. We aimed to provide a broad analysis of different zinc derivatives on proliferation, apoptosis and antimicrobial properties in a simulated nutrient-deficient environment
in vitro. Human fibroblasts (CRL2522) and keratinocytes (HaCaT) were treated with a broad concentration range (10 – 0.0001 µg/mL) of zinc-sulfate (ZnSO
4), -gluconate (ZnGluc) and -histidine (ZnHis) for 1-6 days under nutrient-deficient media conditions. Cell proliferation was investigated by XTT assay. Targeted analyzes in proliferation (
E2F1,
PCNA) and apoptosis (
TP53) associated genes were performed via qRT-PCR and apoptosis was determined via FACS (annexin V/7-AAD staining). Antimicrobial efficacy was investigated using a quantitative suspension method against
S. aureus,
P. aeruginosa,
E. coli, and
C. albicans. The results indicated that 0.1 to 0.001 µg/mL Zn increased cell proliferation in both cell lines. Fibroblasts were more susceptible with significant proliferation peaks on days 2 & 6, and days 1 & 4 for keratinocytes. No relevant changes in gene expression were detected for
E2F1 and
PCNA nor for
TP53. Annexin-V/7-AAD-staining of fibroblasts revealed a small, yet insignificant reduction of apoptosis induction for ZnGluc and ZnSO
4. ZnGluc and ZnSO
4 (0.1%) achieved high microbial reductions (4-5 log
10 reductions) against tested pathogens. ZnGluc and ZnSO
4 showed relevant pro-proliferative and antimicrobial, as well as tendential anti-apoptotic features in a simulated nutrient-deficient microenvironment
in vitro. This further validates a potential benefit of local zinc treatment in deficient wound microenvironments.
Type of Study:
Original Article |
Subject:
Cell Biology Received: 2020/03/16 | Accepted: 2020/07/7 | Published: 2020/06/30