LCZ696 (Sacubitril/valsartan) ameliorates oxidative stress, inflammation, fibrosis and improves renal function beyond angiotensin receptor blockade in CKD.

LCZ696 (Sacubitril/valsartan) ameliorates oxidative stress, inflammation, fibrosis and improves renal function beyond angiotensin receptor blockade in CKD. Am J Transl Res. 2017;9(12):5473-5484 Authors: Jing W, Vaziri ND, Nunes A, Suematsu Y, Farzaneh T, Khazaeli M, Moradi H Abstract Progressive deterioration of kidney function in chronic kidney disease (CKD) is mediated by hypertension, oxidative stress, inflammation, and fibrosis. Renin-angiotensin blockade is commonly used to retard CKD progression. In addition, vasoactive peptides have been shown to reduce blood pressure and exert antioxidant, anti-inflammatory and anti-fibrotic effects. We hypothesized that administration of LCZ696 (sacubitril/valsartan) is more effective than valsartan alone in slowing progression of CKD. Male Sprague Dawley rats underwent sham surgery or 5/6 nephrectomy and after two weeks the CKD animals were randomized to no treatment, valsartan (30 mg/kg), or LCZ696 (60 mg/kg) daily by gavage. Serum, urine and kidney tissue analyses were performed after 8 weeks. The untreated CKD rats exhibited hypertension, proteinuria, tubular and glomerular damage, upregulation of pro-inflammatory, pro-oxidant and pro-fibrotic pathways; reduction in nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and its key target products. LCZ696 administration improved renal function and histology and attenuated most of the molecular markers of oxidative st...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research