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Docosahexaenoic acid‐enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus ‐prone mice
Author(s) -
Fernandes Gabriel,
Rahman Md Mizanur,
Arunabh Bhattacharya,
Chandrasekar Bysani
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.21.5.a47
Subject(s) - docosahexaenoic acid , eicosapentaenoic acid , fish oil , systemic lupus erythematosus , endocrinology , chemistry , fatty acid , kidney , medicine , pharmacology , polyunsaturated fatty acid , biology , biochemistry , disease , fish <actinopterygii> , fishery
The therapeutic efficacy of fish oils (FO) in various human inflammatory diseases still remains unresolved, possibly due to low levels of n‐3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) or lower ratio of DHA to EPA. Since FO enriched with DHA (FO‐DHA) or EPA (FO‐EPA) has become available recently, we investigated their efficacy on survival and inflammatory kidney disease in a well‐established animal model of human SLE. Results show for the first time that FO‐DHA dramatically extends both the median (708 days) and maximal (848 days) lifespan of B/W mice. In contrast, FO‐EPA mice had a median and maximal lifespan of ~384 and 500 days, respectively. Investigations into possible survival mechanisms revealed that FO‐DHA (Vs. FO‐EPA) lowers anti‐dsDNA antibodies in serum and IgG deposition in kidneys. Furthermore, FO‐DHA lowered LPS‐mediated increases in serum IL‐18 levels and caspase‐1‐dependent cleavage of pro‐IL‐18 to mature IL‐18 in kidneys. FO‐DHA also suppressed LPS‐mediated PI3K, Akt, and NF‐κB activation in kidneys. These data indicate that DHA, but not EPA, is the most potent n‐3 fatty acid in suppressing glomerulonephritis and extending lifespan of SLE‐prone B/W mice, possibly through inhibition of IL‐18 expression and IL‐18‐dependent signaling.