Pathogenetic mechanisms of skin hyperpigmentation: A cohort prospective study

Background . Acquired skin hyperpigmentation has a pathogenetic origin in the increased activity of melanocytes and melanin synthesis, as well as its saturation of neighboring keratinocytes. However, the issue of molecular mechanisms of occurrence is not fully disclosed. Maintenance of increased cellular metabolism and synthetic process during melanogenesis requires a large amount of energy and plastic substrates to build cell membranes. Thus, the gas transport function of blood erythrocytes and levels of lipoproteins of different classes in serum in patients with hyperpigmentation seemed relevant to study in order to identify their possible contribution to the pathogenesis of this condition. Objectives . To identify systemic changes in blood parameters in patients with acquired skin hyperpigmentation before and after treatment as well as to assess their possible contribution to the mechanisms of skin hyperpigmentation formation. Methods . A cohort prospective study included 50 women aged 42–44 years, living in Rostov-on-Don, who sought medical care at the clinic of the Davinci Group LLC. The study group, 25 patients with a mean age of 41.88 ± 1.45 years, had hyperpigmentation, and the control group of individuals with a mean age of 41.84 ± 1.57 years did not have hyperpigmentation, having come to the clinic for cosmetic purposes. The laboratory stage of the study was conducted in a laboratory of the Department of General and Clinical Biochemistry No. 1 of the Rostov State Medical University of the Ministry of Health of the Russian Federation. Two groups (25 people each) were formed according to the criterion of presence or absence of hyperpigmentation. The target parameters of the study were screening of lipid and cholesterol profiles in blood serum, and assessment of the 2,3-diphosphoglycerate level and products of carbohydrate metabolism in erythrocytes. Total cholesterol, triacylglycerides, and high-density lipoproteins were determined by enzymatic colorimetric method using a Chronolab AG diagnostic kits (Chronolab, Switzerland). The concentration of low-density lipoproteins was determined by turbidimetric method, while the concentration of very low-density lipoproteins was calculated with the “concentration of triacylglycerides / 5” formula. The level of 2,3-diphosphoglycerate was measured by non-enzymatic analysis in trichloroacetic acid filtrate of hemolyzed erythrocytes, while the concentration of lactate and pyruvate was determined using an automated biochemical analyzer VitaLine-200 (Vital Development Corporation, Russia). The collected database was analyzed using descriptive and comparative statistical analysis in Statistica 12.0 software package (StatSoft, USA). Differences were considered statistically significant at p < 0.05. Results . The study of metabolic features of lipoprotein metabolism of different classes in patients with hyperpigmentation indicated an increase in the levels of certain classes of lipoproteins compared to the control group. A statistically significant increase in the concentration of total cholesterol, triacylglycerides, along with a tendency to a decrease in high-density lipoproteins were observed. The median value of the total cholesterol level in the blood of patients with hyperpigmentation was found to be significantly higher than in the control group by 22.2% relative to the control ( p = 0.003), with a statistically significant increase in the median concentration of triacylglycerides relative to the control ( p = 0.032). Women with clinical manifestations of skin hyperpigmentation showed a 58.5% decrease in pyruvate concentration compared to the control group (p = 0.029), whereas the lactate level was found to be 193.9% higher than in the control group ( p < 0.001). The lactate level in the study group statistically significantly increased after treatment compared to the values before treatment thus approaching the control values ( p = 0.609). Meanwhile, the median concentration of 2,3-diphosphoglycerate in the study group before treatment was higher compared to the median in the control group, albeit the difference was not statistically significant ( p = 0.139). Conclusion . Patients with hyperpigmentation were found to have statistically significantly increased levels of certain classes of lipoproteins, such as triacylglycerides, and total cholesterol in the blood. These changes indicate an ongoing need of cells for synthesis of membrane lipids and maintenance of increased cellular metabolism, which is required for increased regeneration of the epidermis. The obtained data reveal a change in the priority of oxygen distribution in cellular structures and tissues, followed by a significant increase in the level of lactate and the development of local tissue hypoxia.