title: Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice.
abstract: The therapeutic efficacy of individual components of fish oils (FOs) 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. Because 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 systemic lupus erythematosus. Results show for the first time that FO-DHA dramatically extends both the median (658 d) and maximal (848 d) life span of (NZB x NZW)F1 (B x W) mice. In contrast, FO-EPA fed mice had a median and maximal life span of approximately 384 and 500 d, respectively. Investigations into possible survival mechanisms revealed that FO-DHA (versus FO-EPA) lowers serum anti-dsDNA Abs, IgG deposition in kidneys, and proteinuria. Further, 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. Moreover, FO-DHA suppressed LPS-mediated PI3K, Akt, and NF-kappaB activations in kidney. These data indicate that DHA, but not EPA, is the most potent n-3 fatty acid that suppresses glomerulonephritis and extends life span of systemic lupus erythematosus-prone short-lived B x W mice, possibly via inhibition of IL-18 induction and IL-18-dependent signaling.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Md Mizanur
authors.initials: MM
authors.lastname: Rahman
authors.forename: Arunabh
authors.initials: A
authors.lastname: Bhattacharya
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Barnes
authors.forename: Bysani
authors.initials: B
authors.lastname: Chandrasekar
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism; D003314:Corn Oil / Q000008:administration & dosage / Q000627:therapeutic use; D003433:Crosses, Genetic; D004281:Docosahexaenoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D004357:Drug Synergism; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage* / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000378:metabolism; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000627:therapeutic use; D008136:Longevity / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology / Q000503:physiopathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D051379:Mice; D008814:Mice, Inbred NZB; D011507:Proteinuria / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D011897:Random Allocation; D013997:Time Factors
chemical_list: D001323:Autoantibodies; D005395:Fish Oils; D007074:Immunoglobulin G; D018836:Inflammation Mediators; D004281:Docosahexaenoic Acids; D003314:Corn Oil; D015118:Eicosapentaenoic Acid