PROTECTIVE EFFECT OF COX INHIBITORS ON LIPOPOLYSACCHARIDE INDUCED SICKNESS BEHAVIOUR OR NEUROINFLAMMATION AND OXIDATIVE STRESS ON MALE WISTAR RATS
Keywords:
Lipopolysaccharide, Sickness behaviour, COX inhibitors, Oxidative StressAbstract
Objectives: The aim of the study was to evaluate the protective effect of COX inhibitors on lipopolysaccharide induced sickness behaviour or neuro inflammation and oxidative stress on male wistar rats.
Methods: Male albino wistar rats were divided into 8 groups and each group consisting of 6 rats and drug treatment has done for one week. Control group was given normal saline daily by i. p route for 7 days. Negative control group receives saline for 6 days followed by LPS on 7th day. All other group receives Resveratrol, Celecoxib, and Aspirin for 7 days and LPS (inducing agent) was given on 7th day just before half an hour of drug treatment. After 2 hours of drug administration, the animals were subjected to behavioural testing and after analyzing behavioural parameters, the animals were sacrificed by cervical dislocation in order to perform in vitro studies.
Results: The results of this study showed that Celecoxib at 10 and 50 mg/kg p. o. showed no changes in body weight but there is the decrease in the temperature, increase in the locomotor activity, increase in the number of line crossing, head dipping/nose poaking, decrease in the floating time when compared to the negative control group. Resveratrol at 50 and 100 mg/kg p. o. showed a significant increase in the Superoxide Dismutase, Catalase, Glutathione Reductase, and showed significant decrease in the Lipid Peroxide and Nitric Oxide level when compared to the negative control group.
Conclusion: It was finally concluded that Celecoxib showed neuro protective activity and Resveratrol showed anti-oxidant property.
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References
Christian Raetz, Chris Whitfield. Lipopolysaccharide Endotoxins. Annu Rev Biochem 2002;71:635-700.
Hart BL. Biological basis of the behaviour of sick animals. Neurosci Biobehav Rev 1998;12:123-37.
Exton MS. Infection-induced anorexia: active host defence strategy. Appetite 1997;29:369-83.
Murray MJ. Anorexia of infection as a mechanism of host defense. Am J Clin Nutr 1979;32:593-6.
Mullington J, Korth C, Hermann DM, Orth A, Galanos C, Holsboer F, Pollmacher T. Dose-dependent effects of endotoxin on human sleep. Am J Physiol: Regul Integr Comp Physiol 2000;278(4):R947-55.
Maier SF, Wiertelak EP, Martin D, Watkins LR. Interleukin-1 mediates the behavioral hyperalgesia produced by lithium chloride and endotoxin. Brain Res 1993;623:321-4.
Dantzer R, Kelley KW. Twenty years of research on cytokine induced sickness behaviour. Brain Behav Immun 2007;21(2):153–60.
Kelley KW, Bluthé RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, et al. Cytokine-induced sickness behaviour. Brain Behav Immun 2003;17:S 112-S8.
Asehnoune K, Strassheim D, Mitra S, Kim JY, Abraham E. Involvement of reactive oxygen species in Toll-like receptor 4-dependent activation of NF-kappa B. J Immunol 2004;172:2522-9.
Sangeeta Pilkhwal Sah, Naveen Tirkey, Anurag Kuhad, Kanwaljit Chopra. Effect of quercetin on Lipopolysaccharide induced sickness behaviour and oxidative stress in rats. Indian J Pharmacol 2011;43(2):192-6.
JL Teeling, C Cunningham, TA Newman, VH Perry. The effect of non-steroidal anti-inflammatory agents on behavioural changes and cytokine production following systemic inflammation: implications for a role of COX-1. Brain Behav Immun 2010;24:409-19.
Turner RA. Depressant of the central nervous system screening procedure in Pharmacology. Academic press: New York; 1972. p. 78.
Clarice C Veloso, Andressa D Bitencourt, Layla DM Cabral, Lidiane S Franqui. Pyrostegia venusta attenuate the sickness behaviour induced by Lipopolysaccharide in mice. J Ethanopharmacol 2010;132(1):355-8.
Misra H.P. and Fridovich I., The Oxidation of phenylhydrazine: superoxide and mechanisms. Biochemistry, 1976;15:681-687.
Aebi H. Methods of enzymatic analysis, New York: Academic Press; 1974;2:674.
Ohkawa H, Ohisi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J Lab Clin Med 1963;61:882-8.
Raghvendra V, Agrawal JN, Kulkarni SK. Melatonin reversal of lipopolysaccharide-induced thermal and behavioral hyper-algesia in mice. Eur J Pharmacol 2000;395:15–21.
Morrison DC, Ryan JL. Endotoxin and disease mechanisms. Annu Rev Med 1987;38:417-32.
Bellezzo JM, Leingang KA, Bulla GA, Britton RS, Bacon BR, Fox ES. Modulation of Lipopolysaccharide-mediated activation in rat Kupffer cells by antioxidants. J Lab Clin Med 1998;131:36-44.