title: Viper venom-induced oxidative stress and activation of inflammatory cytokines: a therapeutic approach for overlooked issues of snakebite management.
abstract: OBJECTIVE
  The snakebite mortality rate has been significantly reduced due to effective anti-venin therapy. The intravenously infused anti-venom will neutralize free and target-bound toxins but fails to neutralize venom-induced inflammation and oxidative stress, as the antigen-antibody complex itself is pro-inflammatory. Therefore, an auxiliary therapy is necessary to treat secondary/overlooked envenomation complications.
  
  
  METHODS
  Blood samples from healthy donors were treated with viper venom (100 μg/ml) for 2 h. The venom-induced inflammation, oxidative damage and effect of crocin pre-treatment were determined by assessing the serum levels of cytoplasmic, lysosomal and oxidative stress markers along with pro-inflammatory mediators such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and cyclo-oxygenase (COX)-2.
  
  
  RESULTS
  Significantly increased stress markers, cytoplasmic, lysosomal and extracellular matrix-degrading enzymes as well as the pro-inflammatory mediators TNF-α, IL-1β, IL-6 and COX-2 indicated increased cellular damage but significantly reduced oxidative damage and inflammation in crocin pre-treated groups.
  
  
  CONCLUSIONS
  The data clearly suggest that venom-induced oxidative stress and inflammation is also responsible for oxidative burst and cell death in the circulation, which may worsen even after anti-venin therapy. Hence, the current study demands a supportive therapy in addition to anti-venin therapy to neutralize the overlooked issues of snakebite.
authors: Department of Studies in Biochemistry, University of Mysore, Manasagangothri, 570 006 Mysore, Karnataka, India.
authors: M Sebastin
authors: MS
authors: Santhosh
authors: M Shanmuga
authors: MS
authors: Sundaram
authors: K
authors: K
authors: Sunitha
authors: K
authors: K
authors: Kemparaju
authors: K S
authors: KS
authors: Girish
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D002338:Carotenoids / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D012909:Snake Bites; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014757:Viper Venoms / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D016207:Cytokines; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014757:Viper Venoms; D002338:Carotenoids; C029036:crocin; D007770:L-Lactate Dehydrogenase; D002374:Catalase; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D013482:Superoxide Dismutase; D000469:Alkaline Phosphatase; D006026:Glycoside Hydrolases; D006821:Hyaluronoglucosaminidase; D005978:Glutathione
references: Phytother Res. 2010 May;24(5):726-30
references: 19827024
references: Ups J Med Sci. 2012 Mar;117(1):1-9
references: 22283425
references: Curr Top Med Chem. 2011;11(20):2589-600
references: 21682678
references: Cell Mol Life Sci. 2008 Sep;65(18):2897-912
references: 18563294
references: Toxicon. 2008 Dec 15;52(8):908-17
references: 18929590
references: Biochem Pharmacol. 2010 Aug 15;80(4):480-90
references: 20435021
references: Toxicon. 2005 Dec 1;46(7):806-13
references: 16198389
references: Biochem Int. 1989 Nov;19(5):1117-24
references: 2561443
references: Toxicon. 2005 Mar 1;45(3):335-46
references: 15683872
references: Cell Biochem Funct. 2013 Jan;31(1):41-50
references: 22893269
references: Neurotoxicol Teratol. 2000 Mar-Apr;22(2):175-81
references: 10758346
references: Biochem Soc Trans. 2011 Jan;39(1):406-9
references: 21265813
references: Toxicon. 1998 Jan;36(1):207-15
references: 9604294
references: Toxicon. 2000 Sep;38(9):1253-66
references: 10736479
references: Biochim Biophys Acta. 2000 Mar 7;1477(1-2):146-56
references: 10708855
references: Blood Transfus. 2010 Jun;8 Suppl 3:s120-5
references: 20606742
references: J Pineal Res. 2004 Nov;37(4):252-6
references: 15485551
references: Toxicon. 2012 Sep 1;60(3):302-11
references: 22579637
references: Amino Acids. 2010 Mar;38(3):817-27
references: 19381779
references: Life Sci. 2007 May 1;80(21):1921-43
references: 17408700
references: Matrix Biol. 2002 Jan;21(1):25-9
references: 11827789
references: Toxicon. 2005 Jun 15;45(8):951-67
references: 15922768
references: Cell Mol Life Sci. 1997 Feb;53(2):152-5
references: 9118003
references: Cell Biochem Biophys. 2008;51(2-3):89-95
references: 18592145
references: Toxicon. 2007 Apr;49(5):615-24
references: 17241651
references: Ann Hematol. 2011 May;90(5):569-77
references: 20957364
references: Biochimie. 2004 Mar;86(3):193-202
references: 15134834
references: Toxicon. 2012 Feb;59(2):231-40
references: 22155303
references: Anal Biochem. 1979 Jun;95(2):351-8
references: 36810
references: Mini Rev Med Chem. 2013 Jan;13(1):106-23
references: 22876950
references: Curr Med Chem. 2009;16(18):2261-88
references: 19519390
references: J Biochem Mol Toxicol. 2011 May-Jun;25(3):195-203
references: 21671311
references: J Bioenerg Biomembr. 2002 Jun;34(3):227-33
references: 12171072
references: J Biochem Mol Toxicol. 2006;20(2):93-5
references: 16615057
references: Toxicon. 2011 Apr;57(5):627-45
references: 21277886
references: Lancet. 2010 Jan 2;375(9708):77-88
references: 20109866
references: Toxicon. 2009 Jan;53(1):104-14
references: 19013478
references: J Basic Clin Physiol Pharmacol. 2004;15(3-4):277-87
references: 15803963
references: Immunopharmacol Immunotoxicol. 2009;31(4):607-15
references: 19874230
references: Cell Biochem Funct. 2010 Apr;28(3):171-7
references: 20186872
references: Toxicon. 2003 Dec 15;42(8):827-40
references: 15019485
references: Curr Top Med Chem. 2011;11(20):2494-508
references: 21699494
references: PLoS Med. 2008 Nov 4;5(11):e218
references: 18986210
references: Cell Mol Neurobiol. 2010 Mar;30(2):185-91
references: 19711182
references: Biochimie. 2010 Dec;92(12):1854-66
references: 20723574
references: Can J Biochem. 1976 Apr;54(4):350-7
references: 1268758
references: Biochim Biophys Acta. 2012 Jan;1824(1):164-76
references: 21530690
references: Am J Trop Med Hyg. 2008 Nov;79(5):771-8
references: 18981521
references: J Biol Chem. 1951 Nov;193(1):265-75
references: 14907713
references: Mol Cell Biochem. 2002 Nov;240(1-2):105-10
references: 12487377
references: Eur J Pharmacol. 2010 Dec 1;648(1-3):110-6
references: 20854811
references: PLoS Negl Trop Dis. 2011 Sep;5(9):e1312
references: 21909449
references: Toxicon. 2003 Dec 15;42(8):947-62
references: 15019493