title: Naja naja atra Venom Protects against Manifestations of Systemic Lupus Erythematosus in MRL/lpr Mice.
abstract: Systemic lupus erythematosus (SLE) is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration of Naja naja atra venom (NNAV) had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg) or Tripterygium wilfordii polyglycosidium (10 mg/kg) daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Cui
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Jianqun
authors.initials: J
authors.lastname: Kou
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Shuzhi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Yinli
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Han
authors.affiliation: Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Soochow University School of Pharmaceutical Science, Suzhou 215123, China.
authors.forename: Zhenghong
authors.initials: Z
authors.lastname: Qin
references.citation: J Clin Invest. 2005 May;115(5):1232-40
references.pmid: 15841216
references.citation: J Neuroimmunol. 2002 Aug;129(1-2):84-96
references.pmid: 12161024
references.citation: Arch Dermatol Res. 1984;276(3):186-94
references.pmid: 6383229
references.citation: Autoimmun Rev. 2005 Jul;4(6):345-50
references.pmid: 16081025
references.citation: Evid Based Complement Alternat Med. 2013;2013:478049
references.pmid: 23983784
references.citation: Ann Rheum Dis. 2003 Jan;62(1):37-42
references.pmid: 12480667
references.citation: J Exp Med. 1992 Dec 1;176(6):1645-56
references.pmid: 1460423
references.citation: Arthritis Rheum. 1988 Feb;31(2):159-66
references.pmid: 3348821
references.citation: Arthritis Rheum. 1982 Nov;25(11):1271-7
references.pmid: 7138600
references.citation: Evid Based Complement Alternat Med. 2014;2014:287631
references.pmid: 25024726
references.citation: Biol Psychiatry. 2006 May 1;59(9):775-85
references.pmid: 16458261
references.citation: J Am Soc Nephrol. 2001 Jul;12(7):1369-1382
references.pmid: 11423566
references.citation: J Clin Immunol. 2003 Sep;23(5):371-6
references.pmid: 14601645
references.citation: J Rheumatol. 1992 Apr;19(4):562-7
references.pmid: 1593578
references.citation: Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8563-8
references.pmid: 8710910
references.citation: Am J Pathol. 1948 Mar;24(2):389-407
references.pmid: 18904648
references.citation: Autoimmun Rev. 2002 Dec;1(6):321-8
references.pmid: 12848987
references.citation: Acta Pharmacol Sin. 2009 Feb;30(2):219-27
references.pmid: 19169271
references.citation: Rheum Dis Clin North Am. 2000 Feb;26(1):29-50, viii
references.pmid: 10680192
references.citation: Eur Cytokine Netw. 1997 Sep;8(3):281-6
references.pmid: 9346362
references.citation: Arthritis Rheum. 1998 May;41(5):823-30
references.pmid: 9588733
references.citation: Ann Rheum Dis. 1962 Mar;21:70-5
references.pmid: 14494658
references.citation: J Neuroimmunol. 2010 Dec 15;229(1-2):112-22
references.pmid: 20800292
references.citation: Annu Rev Immunol. 1991;9:243-69
references.pmid: 1910678
references.citation: J Rheumatol. 1997 Feb;24(2):303-8
references.pmid: 9034987
references.citation: Eur J Immunol. 2000 Feb;30(2):438-47
references.pmid: 10671199
references.citation: J Nat Toxins. 1998 Feb;7(1):37-44
references.pmid: 9689601
references.citation: J Investig Med. 2004 Jan;52(1):62-71
references.pmid: 14989372
references.citation: Lupus. 2001;10(3):140-7
references.pmid: 11315342
references.citation: Annu Rev Immunol. 2004;22:431-56
references.pmid: 15032584
references.citation: Evid Based Complement Alternat Med. 2013;2013:616241
references.pmid: 23634171
references.citation: Arch Gen Psychiatry. 2008 May;65(5):501-7
references.pmid: 18458201
references.citation: Clin Rheumatol. 1997 May;16(3):275-8
references.pmid: 9184265
references.citation: Lancet. 2011 Feb 26;377(9767):721-31
references.pmid: 21296403
references.citation: Clin Exp Immunol. 1997 Jan;107(1):103-11
references.pmid: 9010264
references.citation: J Clin Invest. 1998 Feb 1;101(3):696-702
references.pmid: 9449705
references.citation: Neurosci Bull. 2006 Sep;22(5):267-73
references.pmid: 17690726
references.citation: J Neuroimmunol. 2004 Jul;152(1-2):83-97
references.pmid: 15223241
references.citation: Annu Rev Pharmacol. 1972;12:265-86
references.pmid: 4339019
references.citation: Int J Dermatol. 1985 Apr;24(3):152-7
references.pmid: 3888878
references.citation: Curr Opin Pediatr. 1999 Dec;11(6):521-7
references.pmid: 10590910
references.citation: Neurosci Biobehav Rev. 2001 May;25(3):235-60
references.pmid: 11378179
references.citation: Ann Rheum Dis. 2008 Mar;67(3):330-4
references.pmid: 17827182
references.citation: Arthritis Rheum. 2011 Aug;63(8):2445-55
references.pmid: 21484768
references.citation: J Exp Med. 1978 Nov 1;148(5):1198-215
references.pmid: 309911
references.citation: Springer Semin Immunopathol. 1994;16(2-3):313-21
references.pmid: 7716711
references.citation: Ann Rheum Dis. 2010 Jan;69(1):20-8
references.pmid: 19103632
references.citation: N Engl J Med. 1996 Nov 28;335(22):1643-9
references.pmid: 8929361
references.citation: Neth J Med. 2003 Nov;61(11):343-6
references.pmid: 14768716
references.citation: J Immunol. 2014 Jun 15;192(12):5599-609
references.pmid: 24842756
references.citation: N Y State J Med. 1950 Oct 15;50(20):2444-5
references.pmid: 14780433
references.citation: J Neuroimmunol. 2005 Aug;165(1-2):104-13
references.pmid: 15972238
references.citation: J Clin Invest. 2003 Feb;111(4):539-52
references.pmid: 12588892
references.citation: Blood. 2001 May 15;97(10):3292-9
references.pmid: 11342461
references.citation: Immunol Rev. 1999 Jun;169:107-21
references.pmid: 10450512
references.citation: Brain Res Bull. 1997;44(2):155-65
references.pmid: 9292205
references.citation: Neurobiol Dis. 2006 Sep;23(3):587-94
references.pmid: 16843000
references.citation: J Immunol. 2014 May 15;192(10):4541-50
references.pmid: 24740509