当前位置： SCI文献检索 > EUROPEAN JOURNAL OF PHARMACOLOGY期刊下所有文献 > Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat.

Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat.

Abstract：

:Receptor for advanced glycation end-products (RAGE) is involved in the pathogenesis of diabetic nephropathy. FPS-ZM1, a selective RAGE inhibitor, in combination with valsartan were investigated for their protective potentials on the renal markers of tubular injury in streptozotocin-induced diabetic rats. Rats were assigned into groups of receiving FPS-ZM1 (1 mg/kg/day), valsartan (100 mg/kg/day), and FPS-ZM1 plus valsartan (1 mg/kg/day and 100 mg/kg/day, respectively) for one month. Kidney histology, renal inflammation and oxidative stress, and renal and urinary markers of tubular injury were investigated. FPS-ZM1 and valsartan in combination more significantly attenuated renal expressions of tumor necrosis factor-alpha and interleukin-6 genes and reduced urinary levels of interleukin-6. Moreover, the combination elevated renal NAD+/NADH ratios and Sirt1 activities, and mitigated nuclear acetylated NF-κB p65 levels. In addition to alleviating indices of oxidative stress i.e. malondialdehyde, superoxide dismutase and glutathione peroxidase, the combination of FPS-ZM1 and valsartan more effectively upregulated the renal levels of master antioxidant proteins Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1. Additionally, this dual therapy ameliorated more efficiently the indices of renal tubular injuries as indicated by decreased renal kidney injury molecule-1 levels as well as reduced urinary levels of cystatin C, retinol binding protein, and beta-2-microglobulin. While FPS-ZM1 alone had no appreciable effects on the renal fibrosis, the combination treatment ameliorated fibrosis better than valsartan in the kidneys. Collectively, these findings underline the extra benefits of FPS-ZM1 and valsartan dual administrations in obviating the renal tubular cell injury in streptozotocin-induced diabetic rats partly by suppressing renal inflammation and oxidative stress.

journal_name

Eur J Pharmacol

journal_title

European journal of pharmacology

authors

Sanajou D,Ghorbani Haghjo A,Argani H,Roshangar L,Rashtchizadeh N,Ahmad SNS,Ashrafi-Jigheh Z,Bahrambeigi S,Asiaee F,Rashedi J,Aslani S

doi

10.1016/j.ejphar.2018.10.035

subject

Has Abstract

pub_date

2019-01-05 00:00:00

pages

40-48

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(18)30617-4

journal_volume

842

pub_type

杂志文章

在线工具

Reduction of renal tubular injury with a RAGE inhibitor FPS-ZM1, valsartan and their combination in streptozotocin-induced diabetes in the rat.