title: Concentrated fish oil (Lovaza(R)) extends lifespan and attenuates kidney disease in lupus-prone short-lived (NZBxNZW)F1 mice.
abstract: A growing number of reports indicate that anti-inflammatory actions of fish oil (FO) are beneficial against systemic lupus erythematosus (SLE). However, the majority of pre-clinical studies were performed using 5-20% FO, which is higher than the clinically relevant dose for lupus patients. The present study was performed in order to determine the effective low dose of FDA-approved concentrated FO (Lovaza®) compared to the commonly used FO-18/12 (18-Eicosapentaenoic acid [EPA]/12-Docosahexaenoic acid [DHA]). We examined the dose-dependent response of Lovaza® (1% and 4%) on an SLE mouse strain (NZBxNZW)F1 and compared the same with 1% and 4% placebo, as well as 4% FO-18/12, maintaining standard chow as the control. Results show for the first time that 1% Lovaza® extends maximal lifespan (517 d) and 4% Lovaza® significantly extends both the median (502 d) and maximal (600 d) life span of (NZBxNZW)F1 mice. In contrast, FO-18/12 extends only median lifespan (410 d) compared to standard chow diet (301 d). Additionally, 4% Lovaza® significantly decreased anti-dsDNA antibodies, reduced glomerulonephritis and attenuated lipopolysaccharide-induced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in splenocytes compared to placebo. 4% Lovaza® was also shown to reduce the expression of inflammatory cytokines, including IL-1β, IL-6 and TNF-α, while increasing renal anti-oxidant enzymes in comparison to placebo. Notably, NFκB activation and p65 nuclear translocation were lowered by 4% Lovaza® compared to placebo. These data indicate that 1% Lovaza® is beneficial, but 4% Lovaza® is more effective in suppressing glomerulonephritis and extending life span of SLE-prone short-lived mice, possibly via reducing inflammation signaling and modulating oxidative stress.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Texas Health Science Center at San Antonio, TX 78229, USA. halade@uthscsa.edu
authors.forename: Ganesh V
authors.initials: GV
authors.lastname: Halade
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Williams
authors.forename: Jyothi M
authors.initials: JM
authors.lastname: Veigas
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Barnes
authors.forename: Gabriel
authors.initials: G
authors.lastname: Fernandes
mesh_terms: D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D051379:Mice
chemical_list: D016207:Cytokines; D015525:Fatty Acids, Omega-3; D005395:Fish Oils
keywords: Fish oil; inflammation; kidney disease; lifespan; lupus; survival
references.citation: Biochem Biophys Res Commun. 1994 Apr 29;200(2):893-8
references.pmid: 8179624
references.citation: Lupus. 1998;7(3):154-8
references.pmid: 9607638
references.citation: J Autoimmun. 1995 Jun;8(3):381-93
references.pmid: 7575999
references.citation: J Cardiovasc Pharmacol. 2011 Jul;58(1):72-9
references.pmid: 21499116
references.citation: Clin Immunol Immunopathol. 1994 Aug;72(2):193-7
references.pmid: 8050192
references.citation: Rheumatology (Oxford). 2012 Mar;51(3):528-34
references.pmid: 22120460
references.citation: Immunity. 2006 Sep;25(3):403-15
references.pmid: 16973390
references.citation: J Immunol. 1985 Dec;135(6):3864-8
references.pmid: 2933453
references.citation: Arthritis Rheum. 2005 Mar;52(3):722-32
references.pmid: 15751097
references.citation: J Bone Miner Res. 2003 Jul;18(7):1206-16
references.pmid: 12854830
references.citation: Lupus. 2004;13(5):344-7
references.pmid: 15230290
references.citation: Clin Rheumatol. 2012 Apr;31(4):717-22
references.pmid: 22124789
references.citation: Mech Ageing Dev. 2004 Sep;125(9):629-32
references.pmid: 15491681
references.citation: J Nutr Biochem. 2010 Dec;21(12):1162-9
references.pmid: 20149618
references.citation: Nat Rev Rheumatol. 2011 May 31;7(7):399-408
references.pmid: 21629241
references.citation: Nutrition. 1995 Sep-Oct;11(5):437-43
references.pmid: 8748195
references.citation: Am J Pathol. 1987 Apr;127(1):106-21
references.pmid: 3565532
references.citation: J Immunol. 2010 May 1;184(9):5280-6
references.pmid: 20368275
references.citation: Am J Kidney Dis. 2010 Oct;56(4):728-42
references.pmid: 20493605
references.citation: J Am Coll Nutr. 2005 Jun;24(3):200-9
references.pmid: 15930486
references.citation: J Nutr Biochem. 2007 Apr;18(4):250-8
references.pmid: 16781858
references.citation: Immunology. 2009 Sep;128(1 Suppl):e306-14
references.pmid: 19016912
references.citation: J Exp Med. 1968 Mar 1;127(3):507-22
references.pmid: 4169964
references.citation: J Nutr Biochem. 2007 Jun;18(6):372-9
references.pmid: 16963250
references.citation: Cell. 1996 May 3;85(3):303-6
references.pmid: 8616885
references.citation: Immunol Lett. 2006 Jan 15;102(1):79-82
references.pmid: 16154204
references.citation: In Vivo. 2005 Sep-Oct;19(5):879-82
references.pmid: 16097442
references.citation: Nature. 1963 Jan 12;197:197
references.pmid: 13953664
references.citation: Arthritis Res Ther. 2011 Jul 06;13(4):228
references.pmid: 21745419
references.citation: Arthritis Rheum. 2004 Jul;50(7):2048-65
references.pmid: 15248202
references.citation: Proc Natl Acad Sci U S A. 1982 Mar;79(6):1974-8
references.pmid: 6979045
references.citation: Pharmacol Res. 2011 May;63(5):377-82
references.pmid: 21345372
references.citation: Complement Ther Med. 2010 Jun-Aug;18(3-4):171-4
references.pmid: 20688263
references.citation: Am Heart J. 2009 Aug;158(2):163-169.e1-3
references.pmid: 19619690
references.citation: N Engl J Med. 2008 Feb 28;358(9):929-39
references.pmid: 18305268
references.citation: J Biomed Biotechnol. 2011;2011:271694
references.pmid: 21403825
references.citation: Cytokine. 1995 Aug;7(6):548-53
references.pmid: 8580371
references.citation: Br J Nutr. 2012 Jun;107 Suppl 2:S171-84
references.pmid: 22591891
references.citation: Cardiovasc Res. 2012 Jan 1;93(1):4-5
references.pmid: 22068160
references.citation: J Nutr Biochem. 2011 May;22(5):459-69
references.pmid: 20656466
references.citation: Br J Nutr. 2009 May;101(10):1517-26
references.pmid: 19245735
references.citation: JPEN J Parenter Enteral Nutr. 2011 Mar;35(2):198-208
references.pmid: 21378249
references.citation: Proc Soc Exp Biol Med. 1990 Jan;193(1):16-22
references.pmid: 2403672
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2010 Apr-Jun;82(4-6):251-8
references.pmid: 20189790
references.citation: Br J Nutr. 1996 May;75(5):711-22
references.pmid: 8695598
references.citation: Lipids. 1994 Aug;29(8):561-8
references.pmid: 7990663
references.citation: Am Fam Physician. 2003 Dec 1;68(11):2179-86
references.pmid: 14677663
references.citation: J Nutr. 2001 Oct;131(10):2753-60
references.pmid: 11584100
references.citation: Clin Chem Lab Med. 2002 Jul;40(7):684-8
references.pmid: 12241014
references.citation: J Nutr. 1986 Sep;116(9):1830-40
references.pmid: 3531437
references.citation: Hypertension. 2006 Nov;48(5):988-93
references.pmid: 16982954