ABSTRACT
The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function.
Subject(s)
Acute Kidney Injury , Hepatitis A Virus Cellular Receptor 1 , Lipocalin-2 , Lithium Carbonate , Animals , Lipocalin-2/metabolism , Mice , Acute Kidney Injury/metabolism , Acute Kidney Injury/chemically induced , Lithium Carbonate/administration & dosage , Hepatitis A Virus Cellular Receptor 1/metabolism , Male , Melanoma, Experimental/metabolism , Melanoma, Experimental/drug therapy , Melanoma, Experimental/pathology , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Skin Neoplasms/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/drug therapy , Biomarkers/metabolism , Biomarkers/bloodABSTRACT
High levels of autophagy can increase the viability of tumor cells as well as their resistance to chemotherapy. Evaluation of the dynamics of autophagy processes at different stages of carcinogenesis can extend our understanding of melanoma pathogenesis to develop new therapeutic approaches. We performed a comparative study of tumor cell autophagy in stages II and III human skin melanoma. Tumor cells were characterized by high content of structures associated with autophagy (autophagosomes and autolysosomes). In stage III melanoma characterized by the presence of regional metastases in the lymph nodes, tumor cells showed higher expression of the autophagy marker protein LC3beta in comparison with stage II melanoma cells, which can indicate the involvement of autophagy processes in tumor progression and the formation of metastases in the lymph nodes.
