Sensibilização inflamatória de células tubulares renais humanas (HK-2) pelo tratamento com albumina controle ou modificada por glicação avançada complexada com ácidos graxos livres

Abstract

Hyperglycemia, coupled with the formation of advanced glycation products (AGE), and dyslipidemia favor the development of diabetic kidney disease (DKD). leading to the need for renal replacement therapies and a reduction in life expectancy. The effect of control or AGE-modified albumin, complexed with fatty acids, on viability and inflammatory sensitization in human renal tubular cells (HK-2) was evaluated. Control and AGE albumin (modified with glycolaldehyde) were complexed with palmitic or oleic acid (0.1, 0.25, and 0.5mM) by vortexing and incubated with HK-2 cells for 48 h. Subsequently, the cells were exposed to either the absence or presence of LPS (1μg/mL) for an additional 24 h. Interleukin 6 (IL-6) and interleukin 1beta (IL-1beta) levels were measured using ELISA, and cell viability was assessed by monitoring the release of lactate dehydrogenase. Cell viability was not consistently affected in all experimental conditions. Control and AGE albumin with palmitic acid exhibited a dose-dependent induction of IL-1beta secretion, which was further potentiated by LPS. Notably, AGE albumin with 0.25mM palmitic acid increased IL-6 compared to control and 0.1mM, while IL-6 secretion was reduced by 0.5mM palmitic acid in the presence of LPS compared to control. However, it increased in incubations with AGE albumin complexed with 0.25mM palmitic acid. AGE albumin alone or complexed with 0.1mM palmitic acid promoted a reduction in IL-6 and an increase in IL-1beta compared to control albumin. In the case of oleic acid, both control and AGE albumin with 0.1mM oleic acid increased IL-6 in the absence or presence of LPS. However, IL-1beta increased only with AGE albumin complexed with oleic acid, particularly following LPS treatment. The results underscore the significant role of palmitic and oleic acid in the inflammatory sensitization of HK-2 cells, highlighting the intricate interactions between AGE albumin and fatty acids in the context of DKD.