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Dietary ω‐3 PUFA‐derived NPD1 is renoprotective and augments cytoprotective heme oxygenase‐1 expression in ischemic renal injury
Author(s) -
Hassan Iram Rehnuma,
Gronert Karsten
Publication year - 2007
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.21.6.lb85-a
Subject(s) - fish oil , heme oxygenase , polyunsaturated fatty acid , renal function , docosahexaenoic acid , creatinine , kidney , eicosapentaenoic acid , corn oil , endogeny , medicine , acute kidney injury , pharmacology , chemistry , endocrinology , fatty acid , biochemistry , heme , biology , enzyme , fish <actinopterygii> , fishery
Ischemic acute renal failure (ARF) is a clinical problem associated with high morbidity and mortality, and inflammation is a key feature of its pathophysiology. Fish oil contains the essential ω‐3 polyunsaturated fatty acid (PUFA) docosahexaenoic (DHA) acid which has anti‐inflammatory effects and can ameliorate ARF in animal models. The molecular mechanisms of action for the protective effects of DHA have been attributed to the formation of DHA‐derived lipid mediators (LM), namely neuroprotectin D1 (NPD1) and 17‐HDHA. We set out to investigate if the protective actions of dietary DHA in ischemic renal injury are mediated by DHA‐derived LM. Ischemic injury was induced by clamping the renal pedicle and inflammatory markers and renal function were measured in mice placed on a standard, DHA‐enriched fish oil, or a corn oil diet. Endogenous formation of DHA‐derived LM was analyzed by LC/MS/MS and impact of systemic NPD1 was investigated. 30 min of ischemia elevated serum creatinine in the corn oil diet group by 156%, in contrast, renal function remained normal in the fish oil diet group. Severe ischemic injury (45 min) caused 100% mortality in corn oil fed mice in sharp contrast to 0% in fish oil fed mice. Fish oil diet suppressed PMN influx by 62%, PGE 2 by 57%, and also attenuated levels of MIP‐2, KC, IL‐1β, IL‐6, and TNF‐α, which correlated with endogenous formation of NPD1 and 17‐HDHA in the kidney. Systemic treatment with NPD1 reduced PMN levels in the kidney by 64% and, more importantly, amplified renoprotective heme oxygenase‐1 (HO‐1) protein and mRNA expression in the kidney and in cultured mesangial cells. Taken together, these findings demonstrate that NPD1 mediates, in part, the beneficial effects of dietary DHA in ischemic renal injury and identify amplification of cytoprotective HO‐1 as a potential mechanism.