Influence of distant tumor growth and lithium treatment on ultrastructural organization of kidney proximal tubules

ABSTRACT

Tumor growth causes significant metabolic disturbances, tissue damage and the accumulation of toxic metabolites in the blood. The kidney is an organ with highly developed capillary network and therefore can be exposed to toxic metabolites. Here, the proximal renal tubule cells were studied by immunohistochemistry and electron microscopy, on a model of hepatocellular carcinoma-29 growth in the thigh of CBA mice and lithium carbonate treatment. An increase of autophagy markers (LC3 and LAMP-1) expression was revealed under conditions of distant tumor growth and especially after lithium carbonate treatment. Under conditions of distant tumor we found decrease of numerical density of endosomes and dense apical tubules in the apical part of the cells. In the perinuclear cell compartment, there were swelling of mitochondria and a decrease in their cristae, a decrease of volume density of rough endoplasmic reticulum and the presence of autophagosomes and autolysosomes. The use of lithium carbonate led to an increase of autophagic structures volume density and of dense apical tubules numerical density in the proximal tubule cells. It is possible that the activation of autophagy by lithium can promote an increase in protein recycling in the proximal tubule cells.

KEYWORDS:

• Tumor
• lithium
• proximal tubule cells
• endocytosis
• autophagy

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Institute of Clinical and Experimental Lymphology (Protocol 140; April 26, 2018).

Disclosure statement

The author(s) have declared that no conflict of interest exists.

Author contribution

NB – conception and design of research, analysed data, interpreted results of experiments, drafted manuscript; IT and MV – edited manuscript; NB and IT – prepared figures and approved final version of manuscript.

Additional information

Funding

This work was supported with financing of the Research Institute of Clinical and Experimental Lymphology as part of a state order, Russian Academy of Sciences [0324-2019-0045].