In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 305, No. 11 ( 2013-12-01), p. F1533-F1541
Abstract:
Adriamycin (ADR) administration in susceptible rodents such as the BALB/c mouse strain produces injury to the glomerulus mimicking human focal glomerular sclerosis. The goal of the present study was to use this model to investigate antiproteinuric action of nitro-oleic acid (OA-NO 2 ), a nitric oxide-derived endogenous lipid product, which has exhibited multiple attractive signaling properties particularly in the kidney. BALB/c mice were pretreated for 2 days with OA-NO 2 at 5 mg·kg −1 ·day −1 via an osmotic minipump, followed by a single injection of vehicle or adriamycin (10 mg/kg) via the tail vein. Albuminuria and renal function were analyzed at 1 wk post-ADR treatment. ADR mice developed prominent albuminuria, hypoalbuminemia, hyperlipidemia, and severe ascites. In contrast, the symptoms of nephrotic syndrome were greatly improved by OA-NO 2 treatment. In parallel, plasma creatinine and plasma urea nitrogen were elevated in the ADR group, and the severity was less in the ADR+OA-NO 2 group. OA-NO 2 attenuates ADR-induced glomerulosclerosis, podocyte loss, and tubulointerstitial fibrosis. Indices of oxidative stress, including plasma and urinary thiobarbituric acid-reactive substances and renal expression of NAD(P)H oxidase p47 phox and gp91 phox , and inflammation, including renal expression of TNF-α, IL-1β, and MCP-1 in response to ADR, were all similarly suppressed. Together, these findings suggest that OA-NO 2 exerts renoprotective action against ADR nephropathy likely via its anti-inflammatory and antioxidant properties.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00656.2012
Language:
English
Publisher:
American Physiological Society
Publication Date:
2013
detail.hit.zdb_id:
1477287-5
