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Docosahexaenoic Acid Ameliorates Murine Ischemic Acute Renal Failure and Prevents Increases in mRNA Abundance for both TNF- and Inducible Nitric Oxide Synthase

Mariusz L. Kielar^*, D. Rohan Jeyarajah, X. J. Zhou and Christopher Y. Lu^*,

*Departments of Internal Medicine, Division of Nephrology, Surgery, Division of GI/Endocrine Surgery, Pathology, and Graduate Program in Immunology, University of Texas Southwestern Medical Center, Dallas, Texas.

Correspondence to Dr. Christopher Y. Lu, Division of Nephrology, Dept. of Internal Medicine, U. Texas Southwestern Medical Center, Dallas, TX 75390-8856. Phone: (214)-648-2889; Fax: (214) 648-2071;

ABSTRACT. This study demonstrates that intraperitoneal injections of DHA (all cis 4,7,10,13,16,19 docosahexaenoic acid C22: n-3) bound to bovine serum albumin ameliorate murine acute renal failure (ARF) induced by temporary occlusion of the renal artery. Three micromoles of DHA decreased serum creatinine (Scr) from 2.3 mg/dl to 1.1 mg/dl 24 h after reperfusion (n = 15; P < 0.05). Scr of the treated animals were significantly lower than controls throughout a 7-d time course. Although lower doses of DHA were less effective, higher doses were not more effective. Ribonuclease (RNase) protection assays showed that ischemia increased mRNA abundance for TNF- and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF- and iNOS contribute to renal ischemic injury, their inhibition may contribute to DHA’s salutary effect. In addition, the data may have therapeutic implications, because the DHA improves ARF even when administered at 4 h after reperfusion. Email: christopher.lu@utsouthwestern.edu

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673