Nimesulide effects on the blood pro-oxidant–antioxidant status in lipopolysaccharide-challenged mice
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.
KeywordsAntioxidant defence Lipopolysaccharide Lipid peroxidation Nimesulide Mice
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.
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.
- 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
- Andreeva LI, Kozhemyakin LA, Kishkun AA (1988) A modified thiobarbituric acid test for measuring lipid peroxidation. Lab Delo 11:41–43Google Scholar
- 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
- 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
- Beutler E, Duron O, Kelly BM (1963) Improved method for determination of blood glutathione. J Lab Med 61:882–888Google Scholar
- Callahan GN, Yates RM, Warren AL (2014) Basic veterinary immunology. University Press of Colorado, Boulder, p 80303Google Scholar
- 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 17:1481–1489CrossRefPubMedPubMedCentralGoogle Scholar
- 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
- Held P (2015) An introduction to reactive oxygen species. Measurement of ROS. in Cell BioTek Rev 1–26Google Scholar
- Israelachvili JN (2010) Intermolecular and surface forces. Academic Press, LondonGoogle Scholar
- 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 100:2652–2661CrossRefPubMedPubMedCentralGoogle Scholar
- 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
- Liu M, Bing G (2011) Lipopolysaccharide animal models for Parkinson’s disease. Parkinson’s Dis. https://doi.org/10.4061/2011/327089
- 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
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- Noori S (2012) An overview of oxidative and antioxidant defensive system. Open Access Sci Rep 1(8):1–9Google Scholar
- 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 CrossRefPubMedPubMedCentralGoogle Scholar
- 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
- 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
- Uchiyama M, Michara M (1978) Determination of malondialdehyde precursor in tissues by thiobarbituric acid test. Biochemistry 86:271–278Google Scholar
- 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 8:419–425CrossRefPubMedGoogle Scholar