Histopathological changes in the spleen of rats exposed to N,N-dimethylhydrazine with the following protective input of Au/Ag/Fe

Abstract

Colon cancer is one of the leading causes of cancer-related deaths worldwide. Despite the growing number of studies on nanoparticles of different metals, there is still a lack of reliable information about their ability to work together as a composition and their antitumor effects. It has been established that the regulation of genes encoding proteins of the Bcl-2 family changes in cancer. Bcl-2 family proteins can be a potential target in cancer diagnosis and have a prognostic value in treating cancer with chemotherapeutic drugs. The tumor microenvironment includes myeloid suppressor cells, tumor-associated neutrophils, and tumor-associated macrophages that promote cancer progression and are derived from splenic hematopoietic stem cells and progenitor cells. The work aimed to ascertain histological changes and expression of Bcl-2 family proteins in the spleen of rats with N,N-dimethylhydrazine-induced carcinogenesis followed by the protective administration of Au/Ag/Fe nanometal composition. The study was conducted on 72 outbred white male rats. Colon adenocarcinoma was modelled by N,N-dimethylhydrazine hydrochloride administration for 30 weeks. Animals received an aqueous dispersion of Au/Ag/Fe nanoparticles intragastrically once a day for 21 days at a dose of 0.842 mg Ag/0.0526 mg Fe/1.625 μg Au per 1 kg of rat body weight. Paraffin sections of the spleen were stained with hematoxylin and eosin. For immunohistochemical analysis, sections were stained with rabbit monoclonal antibodies to Bcl-2. Under conditions of 30-week exposure to N,N-dimethylhydrazine hydrochloride, blood circulation disorders, stasis, thrombosis, reduction in the size of white pulp lymphatic nodules and loss of their zonation were histologically proved in the rat's spleen. The development of sclerotic processes in the organ was noted. It was indicated that using metal nanoparticles under N,N-dimethylhydrazine hydrochloride-induced colon carcinogenesis leads to less evidenced morphological manifestations of structural changes in the spleen. Immunohistochemically, the expression of Bcl-2 protein in the white pulp of the spleen of animals subjected to correction was lower than in animals without the corrective effect of the composition of nanoparticle metals. Administration of the Au/Ag/Fe metal nanoparticle composition to intact white rats does not cause pathological changes in the spleen morphology. The structural components of the red and white pulp match the typical histological structure of the organ.