Skip to main content

Advertisement

Log in

Effects of afferent and efferent denervation of vagal nerve on endotoxin-induced oxidative stress in rats

  • Neurology and Preclinical Neurological Studies - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

This study investigated the role of vagal innervation in oxidative stress after systemic administration of lipopolysaccharide (LPS) endotoxin. Control rats and rats subjected to bilateral subdiaphragmatic vagotomy, perivagal capsaicin application (5 mg/ml) or cholinergic receptor blockade with subcutaneous atropine (1 mg/kg), were intraperitoneally injected with 300 μg/kg of LPS and euthanized 4 h later. Results indicated that; (1) surgical vagotomy and sensory denervation by perivagal capsaicin increased brain oxidative stress and decreased reduced glutathione in basal condition (saline-treated rats) and following endotoxin challenge; (2) oxidative stress decreased after cholinergic blockade with atropine in endotoxemic rats; (3) nitric oxide decreased by abdominal vagotomy, sensory deafferentation and cholinergic blockade after endotoxin injection; (4) liver lipid peroxidation decreased after surgical vagotomy and cholinergic blockade but increased after sensory deafferentation; (5) liver reduced glutathione decreased following vagotomy and sensory denervation in basal state and by cholinergic blockade in basal state and during endotoxemia; (6) nitric oxide increased by vagotomy in basal state and by sensory denervation and cholinergic blockade in basal state and during endotoxemia; (7) liver histological damage increased by subdiaphragmatic vagotomy, sensory denervation or cholinergic blockade. These findings suggest that: (1) sensory fibers (signals from the periphery) running in the vagus nerves are important in maintaining the redox status of the brain; (2) capsaicin vagal sensory nerves are likely to maintain nitric oxide tone in basal conditions; (3) the vagus nerve modulates liver redox status and nitric oxide release, (4) the vagus nerve mediates protective role in the liver with both cholinergic and capsaicin-sensitive mechanisms being involved.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11
Fig. 12

Similar content being viewed by others

References

  • Abdel-Salam OME, Sleem AA, Hassan NS, Sharaf HA, Gy Mózsik (2006) Capsaicin ameliorates hepatic injury caused by carbon tetrachloride in the rat. J Pharmacol Toxicol 1:147–156

    Article  CAS  Google Scholar 

  • Abdel-Salam OME, Abdel-Rahman RF, Sleem AA, Farrag AR (2012) Modulation of lipopolysaccharide-induced oxidative stress by capsaicin. Inflammopharmacology 20:207–217

    Article  PubMed  CAS  Google Scholar 

  • Alam ZI, Daniel SE, Lees AJ, Marsden DC, Jenner P, Halliwell B (1997) A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69:1326–1329

    Article  PubMed  CAS  Google Scholar 

  • Belfield A, Goldberg DM (1971) Revised assay for serum phenyl phosphatase activity using 4-amino-antipyrine. Enzyme 12:561–573

    PubMed  CAS  Google Scholar 

  • Bernik TR, Friedman SG, Ochani M, DiRaimo R, Ulloa L, Yang H, Sudan S, Czura CJ, Ivanova SM, Tracey KJ (2002) Pharmacological stimulation of the cholinergic antiinflammatory pathway. J Exp Med 195:781–788

    Article  PubMed  CAS  Google Scholar 

  • Berthouda HR, Neuhuberb WL (2000) Functional and chemical anatomy of the afferent vagal system. Auton Neurosci 85:1–17

    Google Scholar 

  • Beurel E, Jope RS (2009) Lipopolysaccharide-induced interleukin-6 production is controlled by glycogen synthase kinase-3 and STAT3 in the brain. J Neuroinflammation 6:9

    Article  PubMed  Google Scholar 

  • Borovikova LV, Ivanova S, Zhang M, Yang H, Botchkina GI, Watkins LR, Wang H, Abumrad N, Eaton JW, Tracey KJ (2000) Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405:458–462

    Article  PubMed  CAS  Google Scholar 

  • Buttini M, Mir A, Appel K, Wiederhold KH, Limonta S, Gebicke-Haerter PJ, Boddeke HW (1997) Lipopolysaccharide induces expression of tumour necrosis factor alpha in rat brain: inhibition by methylprednisolone and by rolipram. Br J Pharmacol 122:1483–1489

    Article  PubMed  CAS  Google Scholar 

  • Crowley LV (1967) The Reitman–Frankel colorimetric transaminase procedure in suspected myocardial infarction. Clin Chem 13:482–487

    PubMed  CAS  Google Scholar 

  • Cunningham C, Wilcockson DC, Campion S, Lunnon K, Perry VH (2005) Central and systemic endotoxin challenges exacerbate the local inflammatory response and increase neuronal death during chronic neurodegeneration. J Neurosci 25:9275–9284

    Article  PubMed  CAS  Google Scholar 

  • Dogan MD, Patel S, Rudaya AY, Steiner AA, Székely M, Romanovsky AA (2004) Lipopolysaccharide fever is initiated via a capsaicin-sensitive mechanism independent of the subtype-1 vanilloid receptor. Br J Pharmacol 143:1023–1032

    Article  PubMed  CAS  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem 82:70–77

    Article  PubMed  CAS  Google Scholar 

  • Fidan H, Sahin O, Ela Y, Kilbas A, Bas O, Yavuz Y, Sahin DA, Altuntas I (2007) Influence of different atropine therapy strategies on fenthion-induced organ dysfunction in rats. Basic Clin Pharmacol Toxicol 100:308–315

    Article  PubMed  CAS  Google Scholar 

  • Fisher AEO, Naughton DP (2003) Redox-active metal ions and oxidative stress: therapeutic implications. Proc Indian Natl Sci Acad B69:453–460

    Google Scholar 

  • Goehler LE, Gaykema RPA, Nguyen KT, Lee JE, Tilders FJH, Maier SF, Watkins LR (1999) Interleukin-1b in immune cells of the abdominal vagus nerve: a link between the immune and nervous systems? J Neurosci 19:2799–2806

    PubMed  CAS  Google Scholar 

  • Goehler LE, Gaykema RP, Hansen MK, Anderson K, Maier SF, Watkins LR (2000) Vagal immune-to-brain communication: a visceral chemosensory pathway. Auton Neurosci 85:49–59

    Article  PubMed  CAS  Google Scholar 

  • Goehler LE, Gaykema RP, Opitz N, Reddaway R, Badr N, Lyte M (2005) Activation in vagal afferents and central autonomic pathways: early responses to intestinal infection with Campylobacter jejuni. Brain Behav Immun 19:334–344

    Article  PubMed  Google Scholar 

  • Goehler LE, Lyte M, Gaykema RP (2007) Infection-induced viscerosensory signals from the gut enhance anxiety: implications for psychoneuroimmunology. Brain Behav Immun 21:721–726

    Article  PubMed  CAS  Google Scholar 

  • Gutteridge JMC (1985) Lipid peroxidation and antioxidants as biomarkers of tissue damage. Clin Chem 41:1819–1828

    Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18:685–716

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97:1634–1658

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B, Gutteridge JMC (2007) Free radicals in biology and medicine, 4th edn. Clarendon Press, Oxford

    Google Scholar 

  • Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255

    Article  PubMed  CAS  Google Scholar 

  • Holzer P (1988) Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 42:739–768

    Article  Google Scholar 

  • Holzer P, Livingston EH, Saria A, Guth PH (1991) Sensory neurons mediate protective vasodilatation in rat gastric mucosa. Am J Physiol 260:G363–G370

    PubMed  CAS  Google Scholar 

  • Hsu CT (1992) The role of the sympathetic nervous system in promoting liver cirrhosis induced by carbon tetrachloride, using the essential hypertensive animal (SHR). J Auton Nerv Syst 37:163–173

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Wang Y, Jiang D, Zhou J, Huang X (2010) The sympathetic–vagal balance against endotoxemia. J Neural Transm 117:729–735

    Article  PubMed  CAS  Google Scholar 

  • Huston JM, Gallowitsch-Puerta M, Ochani M, Ochani K, Yuan R, Rosas-Ballina M, Ashok M, Goldstein RS, Chavan S, Pavlov VA, Metz CN, Yang H, Czura CJ, Wang H, Tracey KJ (2007) Transcutaneous vagus nerve stimulation reduces serum high mobility group box 1 levels and improves survival in murine sepsis. Crit Care Med 35:2762–2768

    Article  PubMed  Google Scholar 

  • Jacewicz M, Czapski GA, Katkowska I, Strosznajder RP (2009) Systemic administration of lipopolysaccharide impairs glutathione redox state and object recognition in male mice. The effect of PARP-1 inhibitor. Folia Neuropathol 47:321–328

    PubMed  CAS  Google Scholar 

  • Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159

    Article  PubMed  CAS  Google Scholar 

  • Layé S, Gheusi G, Cremona S, Combe C, Kelley K, Dantzer R, Parnet P (2000) Endogenous brain IL-1 mediates LPS-induced anorexia and hypothalamic cytokine expression. Am J Physiol Regul Integr Comp Physiol 279:R93–R98

    PubMed  Google Scholar 

  • Li L, Whiteman M, Moore PK (2009) Dexamethasone inhibits lipopolysaccharide-induced hydrogen sulphide biosynthesis in intact cells and in an animal model of endotoxic shock. J Cell Mol Med 13(8B):2684–2692

    Article  PubMed  Google Scholar 

  • Moreno B, Jukes JP, Vergara-Irigaray N, Errea O, Villoslada P, Perry VH, Newman TA (2011) Systemic inflammation induces axon injury during brain inflammation. Ann Neurol 70:932–942

    Article  PubMed  CAS  Google Scholar 

  • Moshage H, Kok B, Huizenga JR (1995) Nitrite and nitrate determination in plasma: a critical evaluation. Clin Chem 41:892–896

    PubMed  CAS  Google Scholar 

  • Mravec B (2010) The role of the vagus nerve in stroke. Auton Neurosci 158:8–12

    Article  PubMed  Google Scholar 

  • Noble F, Rubira E, Boulanouar M, Palmier B, Plotkine M, Warnet JM, Marchand-Leroux C, Massicot F (2007) Acute systemic inflammation induces central mitochondrial damage and mnesic deficit in adult Swiss mice. Neurosci Lett 424:106–110

    Article  PubMed  CAS  Google Scholar 

  • Peterson CY, Krzyzaniak M, Coimbra R, Chang DC (2012) Vagus nerve and postinjury inflammatory response. Arch Surg 147:76–80

    Article  PubMed  Google Scholar 

  • Qin L, Wu X, Block ML, Liu Y, Breese GR, Hong JS, Knapp DJ, Crews FT (2007) Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. Glia 55:453–462

    Article  PubMed  Google Scholar 

  • Quan N, Stern EL, Whiteside MB, Herkenham M (1999) Induction of pro-inflammatory cytokine mRNAs in the brain after peripheral injection of subseptic doses of lipopolysaccharide in the rat. J Neuroimmunol 93:72–80

    Article  PubMed  CAS  Google Scholar 

  • Raybould HE, Taché Y (1989) Capsaicin-sensitive vagal afferent fibers and stimulation of gastric acid secretion in anesthetized rats. Eur J Pharmacol 167:237–243

    Article  PubMed  CAS  Google Scholar 

  • Reiter RJ (1995) Oxidative processes and antioxidative defense mechanisms in the aging brain. FASEB J 9:526–533

    PubMed  CAS  Google Scholar 

  • Romanovsky AA (2004) Signaling the brain in the early sickness syndrome: are sensory nerves involved? Front Biosci 9:494–504

    Article  PubMed  CAS  Google Scholar 

  • Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, Tusche MW, Pavlov VA, Andersson U, Chavan S, Mak TW, Tracey KJ (2011) Acetylcholine-synthesizing t cells relay neural signals in a vagus nerve circuit. Science 334:98–101

    Article  PubMed  CAS  Google Scholar 

  • Ruiz-Larrea MB, Leal AM, Liza M, Lacort M, de Groot H (1994) Antioxidant effects of estradiol and 2-hydroxyestradiol on iron-induced lipid peroxidation of rat liver microsomes. Steroids 59:383–388

    Article  PubMed  CAS  Google Scholar 

  • Sies H (1991) Oxidative stress: introduction. In: Sies H (ed) Oxidative stress: oxidants and antioxidants, Academic Press, London, pp xv–xxii

  • Sies H (1997) Oxidative stress: oxidants and antioxidants. Exp Physiol 82:291–295

    PubMed  CAS  Google Scholar 

  • Sies H, Jones DP (2007) Oxidative stress. In: Fink G (ed) Encyclopaedia of stress. Elsevier, San Diego, pp 45–48

  • Spencer SJ, Mouihate A, Pittman QJ (2007) Peripheral inflammation exacerbates damage after global ischemia independently of temperature and acute brain inflammation. Stroke 38:1570–1577

    Article  PubMed  CAS  Google Scholar 

  • Szolcsányi J (1977) A pharmacological approach to elucidation of the role of different nerve fibers and receptor endings in mediation of pain. J Physiol 73:251–259

    Google Scholar 

  • Szolcsányi J (1984) Capsaicin-sensitive chemoceptive neural system with dual sensory-efferent function. In: Chahl LA, Szolcsányi J, Lembeck F (eds) Antidromic vasodilatation and neurogenic inflammation. Akadémiai Kiadó, Budapest, pp 27–40

    Google Scholar 

  • Szolcsányi J (1990) Capsaicin, irritation, and desensitization: neurophysiological basis and future perspectives. In: Chemical senses. Irritation, vol. 2. Marcel Dekker, New York, pp 141–169

  • Szolcsányi J (1993) Actions of capsaicin on sensory receptors. In: Wood JN (ed) Capsaicin in the study of pain. Academic Press, London, pp l–33

  • Teeling JL, Felton LM, Deacon RM, Cunningham C, Rawlins JN, Perry VH (2007) Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain Behav Immun 21:836–850

    Article  PubMed  CAS  Google Scholar 

  • Tracey KJ (2007) Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest 117:289–296

    Article  PubMed  CAS  Google Scholar 

  • van Westerloo DJ, Giebelen IA, Meijers JC, Daalhuisen J, de Vos AF, Levi M, van der Poll T (2006) Vagus nerve stimulation inhibits activation of coagulation and fibrinolysis during endotoxemia in rats. J Thromb Haemost 4:1997–2002

    Article  PubMed  Google Scholar 

  • Yoritaka A, Hattori N, Uchida K, Tanaka M, Stadtman ER, Mizuno Y (1996) Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease. Proc Natl Acad Sci USA 93:2696–2701

    Article  PubMed  CAS  Google Scholar 

  • Zafra MA, Molina F, Puerto A (2003) Effects of perivagal administration of capsaicin on post-surgical food intake. Auton Neurosci Basic Clin 107:37–44

    Article  CAS  Google Scholar 

  • Zhang J, Perry G, Smith MA, Robertson D, Olson SJ, Graham DG, Montine TJ (1999) Parkinson’s disease is associated with oxidative damage to cytoplasmic DNA and RNA in substantia nigra neurons. Am J Pathol 154:1423–1429

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that there are no conflicts of interest relevant to the subject of their manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Omar M. E. Abdel-Salam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Abdel-Salam, O.M.E., Abdel-Rahman, R.F., Sleem, A.A. et al. Effects of afferent and efferent denervation of vagal nerve on endotoxin-induced oxidative stress in rats. J Neural Transm 120, 1673–1688 (2013). https://doi.org/10.1007/s00702-013-1053-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-013-1053-6

Keywords

Navigation