title: Nitro-oleic acid protects against adriamycin-induced nephropathy in mice.
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-NO2), 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-NO2 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-NO2 treatment. In parallel, plasma creatinine and plasma urea nitrogen were elevated in the ADR group, and the severity was less in the ADR+OA-NO2 group. OA-NO2 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-NO2 exerts renoprotective action against ADR nephropathy likely via its anti-inflammatory and antioxidant properties.
authors.affiliation: Univ. of Utah and Veterans Affairs Medical Center, Div. of Nephrology and Hypertension, 30N 1900E, RM 4C224, Salt Lake City, UT 84132. Tianxin.Yang@hsc.utah.edu.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Liu
authors.forename: Zhanjun
authors.initials: Z
authors.lastname: Jia
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Ling
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Zhou
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Yaomin
authors.initials: Y
authors.lastname: Du
authors.forename: Guangju
authors.initials: G
authors.lastname: Guan
authors.forename: Tianxin
authors.initials: T
authors.lastname: Yang
mesh_terms: D000818:Animals; D001806:Blood Urea Nitrogen; D004195:Disease Models, Animal; D004317:Doxorubicin; D007674:Kidney Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000503:physiopathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019301:Oleic Acid / Q000494:pharmacology*
chemical_list: D019301:Oleic Acid; D004317:Doxorubicin
keywords: OA-NO2; adriamycin; albuminuria; glomerulosclerosis; oxidative stress