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Docosahexaenoic acid attenuates renal injury and inflammation in LPS‐induced acute kidney injury via increased resolvin D2
Author(s) -
Katary Mohamed,
Elsherbini Nehal M.,
Ibrahim Ahmed S.,
AlShabrawey Mohamed,
Elmarakby Ahmed A.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1030.28
Subject(s) - docosahexaenoic acid , inflammation , baicalein , acute kidney injury , endocrinology , tbars , medicine , pharmacology , eicosapentaenoic acid , chemistry , lipopolysaccharide , kidney , oxidative stress , myeloperoxidase , tumor necrosis factor alpha , polyunsaturated fatty acid , lipid peroxidation , fatty acid , biochemistry
The polyunsaturated omega‐3 fatty acid, docosahexaenoic acid (DHA), has a promising role in preventing acute kidney injury (AKI); however; DHA reno‐protective mechanism remains to be elucidated. Our aim is to explore how DHA attenuates lipopolysaccharide (LPS)‐induced AKI. Four groups of wild type C57BL/6 (WT) mice were used in the current study (n=4); control, LPS injected (4 mg/kg i.p), LPS treated with the 12/15‐lipoxygenase (12/15‐LO) inhibitor baicalein (20 mg/kg i.p for 6 days) and LPS treated with DHA (50 mg/kg i.p for 6 days). LPS injection in WT mice showed a significant elevation in markers of renal injury compared to WT control mice (albuminuria was 112±4 vs. 8±1 mg/day and podocalyxin was 3.5±0.6 vs. 0.6±0.1 mg/day in LPS injected mice vs. WT control, P< 0.05). The elevation in renal injury markers were also associated with increases in oxidative stress and inflammation as evident by increased urinary thiobarbituric acid reactive substance (TBARs) and monocyte chemoattractant protein‐1 (MCP‐1), respectively, in LPS injected mice. Treatment of LPS injected mice with either DHA or baicalein significantly reduced markers of renal injury and inflammation. Although DHA or baicalein treatment significantly reduced the elevation in renal intercellular adhesion molecule 1 (ICAM‐1) and tumor necrosis factor‐α (TNF‐α) mRNA expression levels in LPS injected mice, DHA was superior over baicalein in reducing Interleukin‐6 (IL‐6) and IL‐1β and in increasing the anti‐inflammatory IL‐10 in LPS injected mice. DHA reduced renal tubular necrosis and vaculated cells and lowered renal expression of CD45, a marker of leucocyte adhesion, in LPS injected mice. DHA also restored the decrease in plasma resolvin D2 in LPS injected mice. Finally, injection of resolvin D2 decreased markers of renal injury, oxidative stress and inflammation and reduced renal tubular degeneration in LPS‐induced AKI. In conclusion, our data suggest that DHA is a superior treatment over 12/15‐LO inhibitor in preventing LPS‐induced AKI, at least in part, via increased resolvin D2. Support or Funding Information Augusta University intramural Funding