Mercuric Chloride Permeation through Human Skin in vitro: Visualization of intercellular Transport and cellular Uptake in the Stratum Corneum

Abstract

SummaryThe aim of the present study was to visualize the routes of penetration of mercuric chloride through human skin in vitro at the ultrastructural level, and to find out to what extent intra- and extracellular space contribute to the percutaneous transport of the model compound. Dermatomed human skin was subjected to in vitro mercuric chloride diffusion experiments in a bicompartmental polycarbonate diffusion cell. Upon interrupting a diffusion experiment samples were treated with ammonium sulfide vapor to precipitate the mercury as mercuric sulfide, and then processed for transmission electron microscopy (TEM). The presence of mercury in the precipitates was verified using X-ray microcanalysis.An additional series of experiments involved the immersion of freshly excised human plantar callus in mercuric chloride solutions, followed by the same tissue-processing protocol as used for the dermatomed skin samples; the mercury-treated callus samples were likewise subjected to TEM.The results indicate that the intercellular route of transport the stratum corneum predominates, but that after longer transport times, apical corneocytes tend to take up material, leading to a bimodal distribution of mercury: in the apical region of the stratum corneum there is mercury both in- and outside the cells; in the medial and proximal region intercellular transport prevails. There were no signs of a discontinuity in the in-depth distribution of mercury in that an almost impermeable barrier would exist in the lower region of the stratum corneum, as suggested by, e.g., Sharata and Burnette [19, 20]; however, there was evidence of the presence of two types of cells: apical corneocytes, which tend to take up mercuric ions relatively easily, and medial and proximal corneocytes, which are less capable of doing so. Interestingly, the results further indicated that intracellular mercury uptake in the apical, squamous region of the stratum corneum occurred preferentially via the desmosomes. This was also the case in the callus immersion studies. These results suggest that the desmosomes may serve to channel material into corneocytes, especially in the squamous region where the desmosomes are beginning to disintegrate and, hence, the cellular lipid envelopes are leaky. A reservoir function for the apical zone of the stratum corneum is suggested.