Nitro-oleic acid protects against adriamycin-induced nephropathy in mice

• Published in: American journal of physiology. Renal physiology 2013-12, Vol.305 (11), p.F1533-F1541
• Main Authors: Liu, Shanshan, Jia, Zhanjun, Zhou, Li, Liu, Ying, Ling, Hong, Zhou, Shu-Feng, Zhang, Aihua, Du, Yaomin, Guan, Guangju, Yang, Tianxin
• Format: Article
• Language: English
• Subjects: Animals; Blood Urea Nitrogen; Call for Papers; Disease Models, Animal; Doxorubicin; Drug therapy; Kidney Diseases - chemically induced; Kidney Diseases - physiopathology; Kidney Diseases - prevention & control; Kidney Glomerulus - physiopathology; Kidneys; Male; Mice; Mice, Inbred BALB C; Nephrology; Oleic Acid - pharmacology; Oxidative stress; Rodents
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00656.2012

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.