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Introduction. The analysis of worldwide and domestic scientific literature reveals that, for the vast majority of nanoparticles (NPs) composed of various metals and their compounds, the mechanisms of their entry into the organism remain unresolved. Data on their biocompatibility, biotransformation, translocation within organs and tissues, and, importantly, their toxicity are lacking. All these questions require investigation through various methods, among which morphological approaches play a significant role. These approaches, at the cellular, tissue, and organ levels, not only allow for the determination of the nature of the toxic effects of chemical substances but also shed light on the features and patterns of their selective toxicity depending on the routes of exposure and nanoparticle size. One of the target organs for lead is the pancreas, where the metal can accumulate in significant quantities and be excreted in the pancreatic secretion into the lumen of the small intestine, resulting in the prolonged recirculation of metal nanoparticles in the organism. This underscores the relevance and necessity of conducting experimental studies under conditions of subacute intraperitoneal administration of PbS NPs of various sizes (12.5 nm, 100 nm) to rats.
Objective. This study aims to assess the morphofunctional state of the rat pancreas in response to subacute intraperitoneal administration of lead sulfide nanoparticles (PbS NPs), with a particular focus on their prolonged circulation within the organism. Additionally, we investigate the specific toxic effects associated with nanoparticle size variations.
Materials and Methods. The research involved PbS NPs and male Wistar rats (n=24) categorized into three groups (1 control, 2 experimental). Colloidal solutions of two distinct sizes, 12.5 nm and 100 nm, were utilized during the experiment and administered into the abdominal cavity over five days per week, summing up to a total of 30 administrations. The assessment of pancreatic morphology was carried out through established histological techniques and specialized histochemical methods.
Results. It has been established that the intraperitoneal administration of PbS NPs of different sizes (12.5 nm and 100 nm) into the abdominal cavity of rats for a duration of one month is accompanied by the development of interstitial edema and damage to the structure of blood vessel walls. In the exocrine apparatus, dystrophic changes in acinar cells and the degree of their severity are associated with the accumulation of small crystal-like inclusions in their cytoplasm, resulting in a reduction in the number of zymogen granules. Notably, hyperchromatosis of nuclear chromatin and a more significant decrease in the number of zymogen granules in the cytoplasm of cells are evident when 100 nm-sized PbS NPs are administered. In the endocrine apparatus of the pancreas, dystrophic changes in insulocytes are characterized by a decrease in the number of A-F-positive secretory granules in their cytoplasm, which are known to be involved in the secretion processes of the primary hormone, insulin. It has been determined that the administration of 100 nm-sized PbS NPs into the organism results in a twofold reduction in the number of functionally active insulocytes (containing A-F-positive granules) in pancreatic islets (PIs), indicating a more pronounced suppression of their secretory activity compared to the action of 12.5 nm-sized PbS NPs.
Conclusions. The disruption of blood vessel structure and the presence of dense crystal-like inclusions within the cytoplasm of endothelial cells indicate the processes of absorption and penetration into the tissues of the pancreas through its system of hemato-tissue barriers. This is evidenced by their accumulation exclusively in the zymogen granules of acinar cells. From there, they are excreted into the lumen of the small intestine as part of the pancreatic secretion and circulate within the organism. The size of the PbS NPs plays a pivotal role in determining the specific toxic effects, as it governs the specific surface area. The latter likely characterizes the functional activity of nanoparticles within a living organism, including their interactions with proteins.
Keywords: Lead sulfide nanoparticles (PbS NPs), pancreas (PZ), pancreatic islets (PI), zymogen granules, acinar cells, insulocytes.