Docosahexaenoic acid ameliorates murine ischemic acute renal failure and prevents increases in mRNA abundance for both TNF-alpha and inducible nitric oxide synthase.
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-alpha and inducible nitric oxide synthase (iNOS) at 24 h. This increase was prevented by DHA administration. Because TNF-alpha 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.
Kielar
Mariusz L
ML
Department of Internal Medicine, Division of Nephrology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Jeyarajah
D Rohan
DR
Zhou
X J
XJ
Lu
Christopher Y
CY
D058186:Acute Kidney Injury / Q000503:physiopathology*; D000818:Animals; D003404:Creatinine / Q000097:blood; D004281:Docosahexaenoic Acids / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D007511:Ischemia / Q000150:complications*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D012079:Renal Circulation; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D012710:Serum Albumin, Bovine; D003404:Creatinine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse