Abstract 656: N-acetylcystein Reduces Lipid Peroxidation and Advanced Glycation Related to Prevention of Macrophage Endoplasmic Reticulum Stress Induced by Albumin Isolated from Rats With Chronic Kidney Disease
Objective: We analyzed the influence of N-acetylcysteine (NAC) in chronic kidney disease (CKD) rats on the plasma concentration of lipid peroxides (TBARS) and advanced glycation end products (AGE) and on the impact of serum CKD-albumin in the development of macrophage endoplasmic reticulum stress (ERS).
Methods: CKD was induced by 5/6 nephrectomy in 2-month old male Wistar rats. Controls (C) were sham operated. Animals were treated or not with NAC (600mg/L of water). FPLC isolated serum albumin was purified by alchoolic extraction. J774 macrophages were incubated with serum albumin (1mg/mL; 18h) from all groups, and the expression of ERS markers (protein disulfide isomerase - PDI and Grp94 chaperone) determined by immunoblot. Comparisons were done by one-way ANOVA, Student t test.
Results: After 60 days of CKD, body weight was 10% lower in CKD compared to C (p<0.01). This was prevented by NAC. Urea, creatinine, total cholesterol (TC), triglycerides (TG) (mg/dL), urinary protein excretion (mg/24h) (C, n= 31; C+NAC, n=20; CKD, n=74; CKD+NAC, n=32), total AGE and pentosidine (n= 8; fluorescence arbitrary unit) and TBARS (n= 7; nmoL/mL) were higher in CKD (122±8; 0.9±0.07; 151±6; 83±4; 46±2.5; 32620±673; 16700±1370; 6.6±0.5, respectively) and in CKD+NAC (91.4±5; 0.6±0.02; 126±7.5; 73±6; 51±3.5; 24,720±1,114; 10,080±748; 4.5±0.5, respectively) in comparison to C (41±0.9; 0.4±0.03; 76±2.7; 51.5±3; 14±0.9; 21,750±960; 5,314±129; 2±0.2, respectively; p<0.001) and C+NAC (40±0.9; 0.3±0.02; 76±2.6; 68±4; 18.4±1.5; 20,040±700; 5,050±267; 1.8±0.2, respectively; p<0,001). TC, urea, creatinine, total AGE, pentosidine and TBARS were respectively, 17%, 25%, 33%, 24%, 40% and 28% (p<0.01) lower in CKD+NAC, than in CKD. Glycemia was higher in C+NAC (107±4.6) and CKD+NAC (107±2.6) than in C (96±1.8; p<0.05) and CKD (98±1.6; p<0.01), respectively. In macrophages (n=6), CKD albumin increased PDI (5 and 7 times, p<0.01) and Grp94 (66% and 80%, p<0.01) in comparison to C and CKD+NAC-albumin treated cells, respectively.
Conclusion: NAC reduces plasma lipid peroxidation and AGE and abrogates ERS induced by CKD-albumin. This may contribute to attenuate the deleterious effects of CKD-albumin on lipid accumulation in macrophages helping preventing atherogenesis in CKD.
Author Disclosures: J.T. Machado: None. R.T. Iborra: None. F.B. Fusco: None. G. Castilho: None. R.S. Pinto: None. A. Machado-Lima: None. E.R. Nakandakare: None. M.M. Shimizu: None. A. Seguro: None. S. Catanozi: None. M. Passarelli: None.
- © 2014 by American Heart Association, Inc.