Tissue Concentrations of Zinc, Iron, Copper, and Magnesium During the Phases of Full Thickness Wound Healing in a Rodent Model

Abstract

Wound healing is a complex orchestration of processes involving cell proliferation, migration, differentiation, anabolism, and catabolism in order to restore skin continuity. Within these processes, elements such as metallic ions are involved due to their implications in cell behavior and enzymatic activity regulation. This study analyzed the kinetics of zinc, iron, copper and magnesium concentrations in a full thickness open wound rat model over 14 days. We made wounds with a diameter of 6 mm on the back of Lewis rats and let them heal naturally prior to analysis by histology and inductively coupled plasma mass spectrometry analysis. Histological and immunofluorescence analysis confirmed an inflammation phase until 7 days, epithelial proliferation phase from 16 h to 10 days, and remodeling phase from 7 days onward. These defined phases were correlated with the measured metal element kinetics. Zinc concentrations showed an inverted parabolic progression between 30.4 and a maximum of 39.9 μg/g dry weight. Magnesium values had a similar pattern between 283 and 499 μg/g dry weight. Copper concentrations, on the other hand, followed an inverted sigmoid trend with a decrease from 9.8 to 1.5 μg/g dry weight. Iron had a slight decrease in concentration for 24 h followed by an increase to a maximum of 466 μg/g dry weight. In conclusion, zinc, iron, and copper, even though differing in their total mass within the wound, exhibited concentration curve transitions at day 3. Interestingly, this time point correlates with the maximum proliferating keratinocyte rate during the proliferation phase. Electronic supplementary material The online version of this article (10.1007/s12011-018-1600-y) contains supplementary material, which is available to authorized users.

Comparison of Maceration and Ultrasonication for Green Extraction of Phenolic Acids from Echinacea purpurea Aerial Parts

“…While the content of zinc in the plant material was not sufficient to grant the recommended dietary allowances [49], it may likely contribute to wound healing when applied locally, as it has been found that the amount of zinc in the wound increases during the healing process. This may induce the keratinocyte proliferation, as it has been shown that keratinocyte proliferation and differentiation are controlled by zinc [50].…”

MOFs-Based Nitric Oxide Therapy for Tendon Regeneration

“…2h, the concentration of Cu ions released from the NMHK and NMPGA was also analyzed. Similar to the release of NO, the release of Cu ions was also slower in NMPGA when compared with that in NMHK, which would accelerate the healing process [41][42][43]. Thus, the release results demonstrated that NMPGA could provide a suitable microenvironment for tissue regeneration by controlling the release rate of NO and Cu ions.…”

Lower Metal Element Levels in Hypertrophic Scars: A Potential Mechanism of Aberrant Cicatrix Hyperplasia

“…Its microbiome and its physical, chemical, and immune barriers constitute an interactive network that protects individuals from external harm [ 21 ]. The 5 elements tested in the current study strongly influence the functions of skin, with effects on wound healing [ 22 , 23 ], scar formation and contraction [ 24 ], microvasculature blood flow [ 25 , 26 ], and immune function [ 27 ]. A deficiency of these 5 elements may cause skin lesions [ 28 – 30 ], while supplementation may lead to improved skin functions [ 21 , 31 ].…”