Is the lipid metabolism involved in renal cell adaptation to damage by oxalate?

MOREL GOMEZ, EMANUEL; GALLO, ARIEL; FERNÁNDEZ TOME, MARIA DEL CARMEN; CASALI, CECILIA IRENE

Ciudad de Mendoza

Congreso; LVIII Reunión de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular- SAIB 2022; 2022

SAIB

Renal collecting ducts, involved in the urine concentration mechanism, are exposed to wastes comingfrom blood filtration, which includes several nephrotoxic agents, such as antibiotics, diuretics,antineoplastic and cytostatic agents, and renal stones. In this way, calcium oxalate stones are the mostcommon type of kidney stone. Crystal aggregates are harmful to epithelial renal cells and tubularstructures, and that damage could lead to the development of chronic kidney disease. Our previousresults showed that differentiated renal cells treated with oxalate (Ox) for 24 h lost the typical epithelialcobblestone morphology and showed a spindle-shaped morphology characteristic of an epithelialmesenchymal transition. After 48 h of Ox, cells started to recover their morphology and after 72 h of Ox,the epithelium was almost reestablished. Hence, the present study seeks to evaluate whether lipidmetabolism is altered in Ox-exposed epithelial renal cells and its involvement in the epithelium restitutionafter 72 h. To do that, renal epithelial cells MDCK were grown in a hyperosmolar environment (512mOsm/kg H2O) for 72 h to get a differentiated epithelium, and further were incubated for 24, 48, or 72 hin the absence or presence of 1.5 mM Ox. After treatment, cells were harvested, counted, and viability,morphology, and cellular lipid content and composition were evaluated. After 24 h, both phospholipid(PL) endogenous content and synthesis significantly increased in Ox-treated cells, while a tendencytowards higher values was observed in cholesterol (Cho) endogenous content and both triacylglycerides(TAG) endogenous content and synthesis. However, at longer times of exposure, no significant differenceswere observed neither in endogenous content nor lipid synthesis in Ox-treated cells with respect to thecontrol condition. Microscopy images showed that Ox significantly increased the number of lipid droplets(LD) per cell after 24 h of incubation, but surprisingly these were more smalls. Whereas at longer times ofexposure, Ox did not alter the number per cell nor mean area of LD. Taken together, obtained resultsindicate that the lipid metabolism would be involved during the first 24 h of Ox exposure. Nevertheless,further experiments are needed to follow deepening the study of such alterations and its impact on Oxmediated damage.