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Nimesulide effects on the blood pro-oxidant–antioxidant status in lipopolysaccharide-challenged mice

  • Maria Andonova
Original Article

Abstract

The maintenance of the pro-oxidant–antioxidant equilibrium between ROS production and antioxidant protection systems is an important element of systemic defence and requires efficient control. The aim of the study was to monitor the dynamics of antioxidants and lipid peroxidation in mice challenged intraperitoneally with Escherichia coli (O111:B4) lipopolysaccharide (LPS) and to evaluate the antioxidant potential of the non-steroidal anti-inflammatory drug nimesulide. Albino mice were divided into three groups (n = 36). Group I received a single intraperitoneal (i.p.) injection with 25 μg/0.5 mL LPS. Thirty minutes before LPS, group II received orally (p.o.) 100 mg/kg nimesulide. The preparation was administered for 4 days. Group III received only nimesulide at the indicated dose for 4 days. The blood parameters were analysed at hour 0 (prior to treatment applied to each group), post treatment hours 6 and 24, and days 3, 5 and 9. Assayed parameters included catalase, reduced glutathione, albumin, glucose, ferric reducing ability of plasma (FRAP), malondialdehyde and oxidative stress index. LPS induced continuous hypoglycaemia, decreased catalase activity and reduced glutathione, but FRAP and albumin were preserved. The application of nimesulide alone did not alter oxidative stress index and enhanced FRAP. Its co-administration with LPS normalised reduced glutathione, decreased catalase and increased malondialdehyde concentrations and oxidative stress index. The application of nimesulide as antioxidant requires objective evaluation of associated benefits and risks.

Keywords

Antioxidant defence Lipopolysaccharide Lipid peroxidation Nimesulide Mice 

Notes

Acknowledgments

Our heartiest thanks to Mrs. Daniela Ivanova, Faculty of Veterinary Medicine, for her help in assaying oxidative stress parameters and the technical assistance in preparing this manuscript.

Compliance with ethical standards

Statement on animal rights

All institutional and national guidelines for the care and use of animals were followed.

Conflict of interest

The author declares that she has no conflict of interest.

Ethical approval

I, Maria Andonova, declare that in this study all applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

References

  1. Aamir M, Mahmood A, Qaiser J, Anum S, Muhammad W, Muhammad AA (2014) Hepatoprotective investigations of Cyminum dried seeds in nimesulide intoxicated albino rats by phytochemical and biochemical methods. Int J Pharm Pharm Sci 6(4):506–510Google Scholar
  2. Ahmad A, Manjrekar P, Yadav C, Agarwal A, Srikantiah RM, Hegde A (2016) Evaluation of ischemia-modified albumin, malondialdehyde, and advanced oxidative protein products as markers of vascular injury in diabetic nephropathy. Biomark Insights 11:63–68CrossRefGoogle Scholar
  3. Al-Abd AM, Al-Abbasi FA, Nofal SM, Khalifa AE, Williams RO, El-Eraky WI, Nagy AA, Abdel-Naim AB (2014) Nimesulide improves the symptomatic and disease modifying effects of leflunomide in collagen induced arthritis. PLoS One 9(11):e111843CrossRefGoogle Scholar
  4. Andreeva LI, Kozhemyakin LA, Kishkun AA (1988) A modified thiobarbituric acid test for measuring lipid peroxidation. Lab Delo 11:41–43Google Scholar
  5. Arana MJ, Vallespi G, Chinea (2003) Inhibition of LPS-responses by synthetic peptides derived from LBP associates with the ability of the peptides to block LBP-LPS interaction. J Endotoxin Res 9(5):281–291Google Scholar
  6. Arthur JR (2000) The glutathione peroxidases. Cell Mol Life Sci 57(13–14):1825–1835Google Scholar
  7. Bennet A (1999) Overview of nimesulide. Rheumatology 38(suppl.1):1–3CrossRefGoogle Scholar
  8. Bennet A (2001) Nimesulide: a well-established cyclo-oxygenase-2 inhibitor with many other pharmacological properties relevant to inflammatory disease. In: Vale JR, Botting RM (eds) Therapeutic roles of selective COX-2 inhibitors. William Harvey Press, London, pp 524–540Google Scholar
  9. Bennet A, Villa G (2000) Nimesulide: an NSAID that preferentially inhibits COX-2, and has various unique pharmacological activities. Exp Opin Pharmacother 1:277–286CrossRefGoogle Scholar
  10. Benzie FF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem 239:70–76CrossRefGoogle Scholar
  11. Bessone F (2010) Non-steroidal anti-inflammatory drugs: what is the actual risk of liver damage? World J Gastroenterol 16(45):5651–5661CrossRefGoogle Scholar
  12. Beutler E, Duron O, Kelly BM (1963) Improved method for determination of blood glutathione. J Lab Med 61:882–888Google Scholar
  13. Bevilacqua M, Vago T, Baldi G, Renesto E, Dallegri F (1994) Nimesulide decreases superoxide production by inhibiting phosphodiesterase type IV. Eur J Pharmacol 268:415–423CrossRefGoogle Scholar
  14. Bhattacharya PK, Burman B, Roy A, Jamil M, Lyngdoh M, Mishra J (2015) Nimesulide induced leukocytoclastic vasculitis and hepatitis: a case report. SpringerPlus 4:302.  https://doi.org/10.1186/s40064-015-1081-9 CrossRefGoogle Scholar
  15. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. World Allergy Organ J 5(1):9–19CrossRefGoogle Scholar
  16. Buttenschoen K, Radermacher P, Bracht H (2010) Endotoxin elimination in sepsis: physiology and therapeutic application. Langenbeck's Arch Surg 395(6):597–605CrossRefGoogle Scholar
  17. Callahan GN, Yates RM, Warren AL (2014) Basic veterinary immunology. University Press of Colorado, Boulder, p 80303Google Scholar
  18. Choudhary S, Boldogh I, Brasier AR (2016) Inside-out signaling pathways from nuclear reactive oxygen species control pulmonary innate immunity. J Innate Immun 8:143–155CrossRefGoogle Scholar
  19. Cornell RP (1989) Hyperinsulinemia elicited by interleukin-1 and nonlethal endotoxemia in rats. Circ Shock 28:121–130Google Scholar
  20. Das SK, Roy C (2011) The protective role of Benincasa hispida on nimesulide-induced hepatotoxicity in albino rat model. Int J Green Pharm 5:192–197CrossRefGoogle Scholar
  21. Deitschel SJ, Kerl ME, Chang CH (2012) Age-associated changes to pathogen-associated molecular pattern-induced inflammatory mediator production in dogs. J Vet Emerg Crit Care 20(5):494–502CrossRefGoogle Scholar
  22. Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL, Meier DT, Eppler E, Bouzakri K, Wueest S, Muller YD, Hansen AMK, Reinecke M, Konrad D, Gassmann M, Reimann F, Halban PA, Gromada J, Drucker DJ, Gribble FM, Ehses JA, Donath MY (2011) Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide 1 secretion from L cells and alpha cells. Nat Med 17:1481–1489CrossRefGoogle Scholar
  23. Fonseca LA, Goncalves RC, Filho JDR, Girardi FM, Filho WPC, Dias DCR, Bento LD (2016) Influence of selenium and vitamin E supplementation on energy metabolism in horses used in policing activity. Comp Clin Pathol 25:351–355CrossRefGoogle Scholar
  24. Ghosn EEB, Cassado AA, Govoni GR, Fukuhara T, Yang Y, Monack DM, Bortoluci KR, Almeida SR, Herzenberg LA, Herzenberg LA (2010) Two physically, functionally, and developmentally distinct peritoneal macrophage subsets. Proc Natl Acad Sci USA 107:2568–2573Google Scholar
  25. Goth L (1991) A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 196:143–151CrossRefGoogle Scholar
  26. Hayashi Y (2012) Polymixin B hemoperfusion (PMX-F) for severe sepsis and septic shock. Nihon Rinsho 70(2):311–314Google Scholar
  27. Held P (2015) An introduction to reactive oxygen species. Measurement of ROS. in Cell BioTek Rev 1–26Google Scholar
  28. Holowaychuk MK, Birkenheuer AJ, Li J (2012) Alterations in calcium homeostasis in dogs with induced endotoxemia. J Vet Intern Med 26(2):244–251CrossRefGoogle Scholar
  29. Infusino I, Panteghini M (2013) Serum albumin: accuracy and clinical use. Clin Chim Acta 419:15–18CrossRefGoogle Scholar
  30. Israelachvili JN (2010) Intermolecular and surface forces. Academic Press, LondonGoogle Scholar
  31. Jones DP (2000) Redox potential of GSH/GSSG couple: assay and biological significance. Methods Enzymol 348:93–112CrossRefGoogle Scholar
  32. Kaconis Y, Kowalski I, Howe J, Brauser A, Richter W, Razquin-Olazaran I, Inigo-Pestana M, Garidel P, Rossle M, Martinez de Tejada G, Gutsmann T, Brandenburg K (2011) Biophysical mechanisms of endotoxin neutralization by cationic amphiphilic peptides. Biophys J 100:2652–2661CrossRefGoogle Scholar
  33. Khalil NA, Ahmed EM, El-Nassan HB, Ahmed OK, Al-Abd AM (2012) Synthesis and biological evaluation of novel pyrazoline derivatives as anti-inflammatory and antioxidant agents. Arch Pharm Res 35:995–1002CrossRefGoogle Scholar
  34. Kosovrasti VY, Nechev L, Amiji MM (2016) Peritoneal macrophage-specific TNF-α gene silencing in LPS-induced acute inflammation model using CD44 targeting hyaluronic acid nanoparticles. Mol Pharm 13(10):3404–3416CrossRefGoogle Scholar
  35. Krishanappa H (2010) Investigations of toxicologic and immunotoxicologic potential of nimesulide. A thesis, Department of Industrial Biotechnology Dr. MGR Educational and Research Institute University ChennaiGoogle Scholar
  36. Liu M, Bing G (2011) Lipopolysaccharide animal models for Parkinson’s disease. Parkinson’s Dis.  https://doi.org/10.4061/2011/327089
  37. Mishra V, Baines M, Wenstone R, Shenkin A (2005) Markers of oxidative damage, antioxidant status and clinical outcome in critically ill patients. Ann Clin Biochem 42:269–276CrossRefGoogle Scholar
  38. Modi CM, Mody SK, Patel HB, Dudhatra GB, Kumar A, Avale M (2012) Toxicopathological overview of analgesic and anti-inflammatory drugs in animals. J Appl Pharm Sci 02(01):149–157Google Scholar
  39. Navarro J, Obrador E, Pellicer JA, Asensi M, Vina J, Estrela JM (1997) Blood glutathione as an index of radiation-induced oxidative stress in mice and humans. Free Radic Biol Med 22(7):1203–1209CrossRefGoogle Scholar
  40. Nguyen AT, Mandard S, Dray C, Deckert V, Valet P, Besnard P, Drucker DJ, Lagrost L, Grober J (2014) Lipopolysaccharide-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway. Diabetes 63:471–482CrossRefGoogle Scholar
  41. Nohr MK, Dudele A, Poulsen MM, Ebbesen LH, Radko Y, Christensen LP, Jessen N, Richelsen B, Lund S, Pedersen SB (2016) LPS-enhanced glucose-stimulated insulin secretion is normalized by resveratrol. PLoS One 11:e0146840.  https://doi.org/10.1371/journal.pone0146840 CrossRefGoogle Scholar
  42. Noori S (2012) An overview of oxidative and antioxidant defensive system. Open Access Sci Rep 1(8):1–9Google Scholar
  43. Raetzsch CF, Brooks NL, Alderman JM, Moore KS, Hosick PA, Klebanov S, Akira S, Bear JE, Baldwin AS, Mackman N, Combs T (2009) LPS inhibition of glucose production through the TLR4, MYD88, NF-kB pathway. Hepatology 50(2):592–600.  https://doi.org/10.1002/hep.22999 CrossRefGoogle Scholar
  44. Rainsford KD (2006) Nimesulide – a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr Med Res Opin 22(6):1161–1170CrossRefGoogle Scholar
  45. Rainsford KD, Bevilacqua M, Dallegri F, Gago F, Ottonello L, Sandrini G, Tavares IG (2005). In: Nimesulide - actions and uses, Birkhauser Verlag AG, pp 133–244 doi:  https://doi.org/10.1007/3-7643-7410-1_4, Pharmacological properties of nimesulide
  46. Roche MP, Rondeau P, Sing NR, Tarnus E, Bourdon E (2008) The antioxidant properties of serum albumin. FEBS Lett 582:1783–1787CrossRefGoogle Scholar
  47. Ronco C, Piccinni P, Rosner MH (2010) Endotoxemia and endotoxin shock: disease, diagnosis and therapy. Contrib Nephrol Basel, Karger 167:14–24CrossRefGoogle Scholar
  48. Rosenfeld Y, Lev N, Shai Y (2010) Effect of the hydrophobicity to net positive charge ratio on antibacterial and anti-endotoxin activities of structurally similar antimicrobial peptides. Biochemistry 49:853–861CrossRefGoogle Scholar
  49. Singh BK, Tripathi M, Chaudhari BP, Pandey PK, Kakkar P (2012) Natural terpenes prevent mitochondrial dysfunction, oxidative stress and release of apoptotic proteins during nimesulide-hepatotoxicity in rats. PLoS One 7(4):e34200CrossRefGoogle Scholar
  50. Sohi KK, Khanduja KL (2003) Nimesulide affects antioxidant status during acute lung inflammation in rats. Indian J Biochem Biophys 40:238–245Google Scholar
  51. Sozer S, Ortac R, Lermioglu F (2011) An investigation of toxicity potential of nimesulide in juvenile rats. Turk J Pharm 8(2):147–158Google Scholar
  52. Uchiyama M, Michara M (1978) Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Biochemistry 86:271–278Google Scholar
  53. Vogel SN, Henricson BE, Neta R (1991) Roles of interleukin-1 and tumor necrosis factor in lipopolysaccharide-induced hypoglycemia. Infect Immun 59:2494–2498Google Scholar
  54. Watson WH, Chen Y, Jones DP (2003) Redox state of glutathione and thioredoxin in differentiation and apoptosis. Biofactors 17(1–4):307–314CrossRefGoogle Scholar
  55. Wimley WC (2010) Describing the mechanism of antimicrobial peptide action with the interfacial activity model. ACS Chem Biol 5:905–917CrossRefGoogle Scholar
  56. Zheng SX, Mouithys-Mickalad A, Deby-Dupont GP, Deby CMT, Maroulis AP, Labasse AH, Lamy ML, Crielaard JMR, Reginster JYL, Henrotin YE (2000) In vitro study of an antioxidant properties on nimesulide and 4-OH nimesulide: effects on HRP- and luminol-dependent chemiluminescence produced by human chondrocytes. Osteoarthr Cartil 8:419–425CrossRefGoogle Scholar
  57. Zhu L, Crouch RK (1992) Albumin in the cornea is oxidized by hydrogen peroxide. Cornea 11(6):567–572CrossRefGoogle Scholar

Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of General and Clinical Pathology, Faculty of Veterinary MedicineTrakia UniversityStara ZagoraBulgaria

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