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

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-α and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF-α 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