Advertisement

Inflammopharmacology

, Volume 20, Issue 6, pp 331–341 | Cite as

Evaluation of ameliorative effect of quercetin in experimental model of alcoholic neuropathy in rats

  • Kiran S. Raygude
  • Amit D. Kandhare
  • Pinaki Ghosh
  • Arvindkumar E. Ghule
  • Subhash L. BodhankarEmail author
Research Article

Abstract

Objective

The objective of the present investigation was to study the neuroprotective effect of the quercetin in alcohol induced neuropathy in rats.

Materials and methods

Male Wistar rats were administered alcohol (10 gm/kg, 35% v/v, p.o. b.i.d.) for 10 weeks. Alpha tocopherol (vitamin E) was used as a standard drug. Vitamin E (100 mg/kg) and quercetin (10, 20 and 40 mg/kg) were co-administered 1 h after ethanol administration for 10 weeks. Behavioral assessment parameters, such as motor incoordination, tactile allodynia, mechanical and thermal hyperalgesia were recorded in all groups of animals. Meanwhile, motor nerve conduction velocity was also recorded. Biochemical parameters, such as nitric oxide (NO), Na+–K+-ATPase, malondialdehyde (MDA) and myeloperoxidase (MPO) were estimated in sciatic nerve. Apoptosis index was determined with help of DNA fragmentation in sciatic nerve.

Results and discussion

Chronic ethanol administration for 10 weeks resulted in significant (P < 0.001) development of neuropathic pain. Chronic treatment with quercetin (20 and 40 mg/kg) for 10 weeks significantly (P < 0.001) attenuated allodynia, hyperalgesia as well as motor coordination and impaired nerve conduction velocity along with decreased level of membrane-bound Na+–K+-ATPase. It also significantly (P < 0.001) decreased elevated levels of MDA, MPO as well as pro-inflammatory mediators, such as NO. It also decreased the extent of DNA fragmentation. This alteration was more significant in vitamin E treated rats (100 mg/kg). Quercetin is a proven antioxidant that might have decreased the oxidative stress produced by chronic alcoholism.

Conclusion

The present investigation elucidates neuroprotective effect of quercetin in alcohol induced neuropathy through modulation of membrane-bound inorganic phosphate enzyme and inhibition of release of oxido-inflammatory mediators, such as MDA, MPO and NO.

Keywords

Alcoholic neuropathy Allodynia DNA fragmentation Hyperalgesia Malondialdehyde Motor nerve conduction velocity Myeloperoxidase Na+–K+-ATPase Nitric oxide 

Notes

Acknowledgments

The authors would like acknowledge Dr. S. S. Kadam, Vice-Chancellor and Dr. K. R. Mahadik, Principal, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Pune, India, for providing necessary facilities to carry out the study. We are also thankful to the All India Council of Technical and Education (AICTE), India for financial support by awarding GATE Scholarship to one of the author Mr. Raygude Kiran for the research work.

Conflict of interest

The authors declare that there are no conflicts of interest.

References

  1. Amaya F, Oh-hashi K, Naruse Y, Iijima N, Ueda M, Shimosato G et al (2003) Local inflammation increases vanilloid receptor 1 expression within distinct subgroups of DRG neurons. Brain Res 963:190–196CrossRefGoogle Scholar
  2. Arruda JL, Colburn RW, Rickman AJ, Rutkowski MD, DeLeo JA (1998) Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain. Brain Res Mol Brain Res 62:228–235CrossRefGoogle Scholar
  3. Bonting SL (1970) Presence of enzyme system in mammalian tissues. Membrane and ion transport. Wiley, New York, pp 257–263Google Scholar
  4. Bradley PP, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Investig Dermatol 78:206–209CrossRefGoogle Scholar
  5. Cavanagh JB (1964) The significance of the “dying back” process in experimental and human neurological disease. Int Rev Exp Pathol 3:219–267Google Scholar
  6. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL (1994) Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 53:55–63CrossRefGoogle Scholar
  7. Cheesman KH (1993) Lipid peroxidation in biological systems. In: Halliwell B, Aruoma OI (eds) DNA and free radicals. Ellis Horwood, London, pp 12–17Google Scholar
  8. Chiu SY (1993) Channel function in mammalian axons and support cells. In: Dyck PJ (ed) Peripheral neuropathy. WB Saunders, Philadelphia, pp 94–108Google Scholar
  9. Cora KC, Cecil RPA (1996) Vasorelaxing activity of reverastrol and quercetin in isolated rat aorta. Gen Pharmacol 27:363–366CrossRefGoogle Scholar
  10. Dobretsov M, Romanovsky D, Stimers JR (2007) Early diabetic neuropathy: triggers and mechanisms. World J Gastroenterol 14:175–191Google Scholar
  11. DokGo H, Lee KH, Kim HJ, Lee EH, Lee J, Songb YS, Lee YH, Jin C, Lee YS, Cho J (2003) Neuroprotective effects of antioxidative flavonoids, quercetin (1)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten. Brain Res 965:130–131CrossRefGoogle Scholar
  12. Ishikawa Y, Kitamura M (2000) Anti-apoptotic effect of quercetin: intervention in the JNK- and ERK-mediated apoptotic pathways. Kidney Int 58:1078–1087CrossRefGoogle Scholar
  13. Jones BJ, Roberts DJ (1968) The quantitative measurement of motor incoordination in naive mice using an accelerating rotarod. J Pharm Pharmacol 20:302–304CrossRefGoogle Scholar
  14. Jung WY, Park SJ, Park DH, Kim JM, Kim DH, Ryu JH (2010) Quercetin impairs learning and memory in normal mice via suppression of hippocampal phosphorylated cyclic AMP response element-binding protein expression. Toxicol Lett 197(2):97–105CrossRefGoogle Scholar
  15. Juntunen J, Teravainen H, Eriksson K, Panula P, Larsen A (1978) Experimental alcoholic neuropathy in the rat: histological and electrophysiological study on the myoneural junctions and the peripheral nerves. Acta Neuropathol (Berl) 4:131–137CrossRefGoogle Scholar
  16. Kahraman A, Erkasap N, Koken T, Serteser M, Aktepe F, Erkasap S (2003) The antioxidative and antihistaminic properties of quercetin in ethanol-induced gastric lesions. Toxicology 183:133–142CrossRefGoogle Scholar
  17. Krawisz JE, Sharon P, Stenson WF (1984) Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gasteroenterology 87:1344–1350Google Scholar
  18. Kumar A, Goyal R (2008) Quercetin protects against acute immobilization stress-induced behaviors and biochemical alterations in mice. J Med Food 11(3):469–473CrossRefGoogle Scholar
  19. Levy D, Zochodne DW (2004) NO pain: potential roles of nitric oxide in neuropathic pain. Pain Pract 4:11–18CrossRefGoogle Scholar
  20. Lin Q, Wu J, Peng YB, Cui M, Willis WD (1999) Nitric oxide-mediated spinal disinhibition contributes to the sensitization of primate spinothalamic tract neurons. J Neurophysiol 81:1086–1094Google Scholar
  21. Liu CM, Zheng YL, Lu J, Zhang ZF, Fan SH, Wu DM, Ma JQ (2010) Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environ Toxicol Pharmacol 29:158–166CrossRefGoogle Scholar
  22. Lowry OH, Rosenbrough NJ, Farr AC, Randell RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275Google Scholar
  23. Mansouri A, Demeilliers C, Amsellem S, Pessayre D, Fromenty B (2001) Acute ethanol administration oxidatively damages and depletes mitochondrial DNA in mouse liver, brain, heart, and skeletal muscles: protective effects of antioxidants. J Pharmacol Exp Ther 298:737–743Google Scholar
  24. Mantle D, Preedy VR (1999) Free radicals as mediators of alcohol toxicity. Adverse Drug React Toxicol Rev 18:235–252Google Scholar
  25. Mawdsley C, Mayer RF (1965) Nerve conduction in alcoholic neuropathy. Brain 88:335–356CrossRefGoogle Scholar
  26. McDonough KH (2003) Antioxidant nutrients and alcohol. Toxicology 189:89–97CrossRefGoogle Scholar
  27. Michael GJ, Priestley JV (1999) Differential expression of the mRNA for the vanilloid receptor subtype 1 in cells of the adult rat dorsal root and nodose ganglia and its down regulation by axotomy. J Neurosci 19:1844–1854Google Scholar
  28. Miranda K, Espy MG, Wink DA (2001) A rapid and simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71CrossRefGoogle Scholar
  29. Miyoshi K, Narita M, Takatsu M, Suzuki T (2007) MGlu5 receptor and protein kinase C implicated in the development and induction of neuropathic pain following chronic ethanol consumption. Eur J Pharmacol 562:208–211CrossRefGoogle Scholar
  30. Monforte R, Estruch R, Valls-Solé J, Nicolás J, Villalta J, Urbano-Marquez A (1995) Autonomic and peripheral neuropathies in patients with chronic alcoholism. A dose-related toxic effect of alcohol. Arch Neurol 52(1):45–51CrossRefGoogle Scholar
  31. Morani A, Bodhankar S (2008) Neuroprotective effect of vitamin E acetate in models of mononeuropathy in rats. Neuroanatomy 7:33–37Google Scholar
  32. Narita M, Miyoshi K, Narita M, Suzuki T (2007) Involvement of microglia in the ethanol-induced neuropathic pain-like state in the rat. Neurosci Lett 414:21–25CrossRefGoogle Scholar
  33. Necker R, Hellon RF (1978) Noxious thermal input from the rat tail: modulation by descending inhibitory influences. Pain 4:231–242CrossRefGoogle Scholar
  34. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefGoogle Scholar
  35. Pace A, Giannarelli D, Galiè E, Savarese A, Carpano S, Della Giulia M, Pozzi A, Silvani A, Gaviani P, Scaioli V, Jandolo B, Bove L, Cognetti F (2010) Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology 74(9):762–766CrossRefGoogle Scholar
  36. Randall LO, Selitto J (1957) A method for measurement of analgesic activity of inflamed tissue. Arch Int Pharmacodyn Ther 111:209–219Google Scholar
  37. Read MA (1995) Flavonoids: naturally occurring anti-inflammatory agents. Am J Pathol 147:235–237Google Scholar
  38. Slater TF, Sawyer BC (1971) The stimulatory effects of carbon tetrachloride and other halogenoalkanes or peroxidative reactions in rat liver fractions in vitro. Biochem J 123:805–814Google Scholar
  39. Tiwari SK, Khan AA, Ahmad KS, Ahmed I, Kauser F, Hussain MA, Ali SM, Alvi A, Habeeb A, Abid Z, Ahmed N, Habibullah CM (2005) Rapid diagnosis of H. pylori infection in dyspeptic patients using salivary secretion: a non invasive approach. Singapore Med J 46:224–228Google Scholar
  40. Tiwari V, Kuhad A, Chopra K (2009) Tocotrienol ameliorates behavioral and biochemical alterations in the rat model of alcoholic neuropathy. Pain 145(1–2):129–135CrossRefGoogle Scholar
  41. Torrejais MM, Soares JC, Matheus SMM, Cassel FD, Mello JM, Basso NA (2002) Histochemical and SEM evaluation of the neuromuscular junctions from alcoholic rats. Tissue Cell 34:117–123CrossRefGoogle Scholar
  42. Tredici G, Minazzi M (1975) Alcoholic neuropathy: an electron-microscopic study. J Neurol Sci 25:333–346CrossRefGoogle Scholar
  43. Valensi P, Le Devehat C, Richard JI, Khodabandehlou T, Rosenbloom RA, LeFante C (2005) A multicenter, doubleblind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications 19:247–253CrossRefGoogle Scholar
  44. Villalta J, Estruch R, Antunez E, Valls J, Urbano-Marquez A (1989) Vagal neuropathy in chronic alcoholics: relation to ethanol consumption. Alcohol Alcohol 24:421–428Google Scholar
  45. Willer JC, Dehen H (1997) Perspective importance of different electrophysiological parameters in alcoholic neuropathy. J Neurol Sci 33:387–396CrossRefGoogle Scholar
  46. Yukari S, Desai SP, Haderer AE, Shinji S, Peter G, Anthony DC, Umberto DG, Ging KW (2004) Neurologic and histopathologic evaluation after high-volume intrathecal amitriptyline. Reg Anesth Pain Med 29:434–440Google Scholar
  47. Zelenka M, Schafers M, Sommer C (2005) Intraneural injection of interleukin-1beta and tumor necrosis factor-alpha into rat sciatic nerve at physiological doses induces signs of neuropathic pain. Pain 116:257–263CrossRefGoogle Scholar
  48. Zimmermann M (2001) Pathobiology of neuropathic pain. Eur J Pharmacol 429:23–37CrossRefGoogle Scholar

Copyright information

© Springer Basel AG 2012

Authors and Affiliations

  • Kiran S. Raygude
    • 1
  • Amit D. Kandhare
    • 1
  • Pinaki Ghosh
    • 1
  • Arvindkumar E. Ghule
    • 1
  • Subhash L. Bodhankar
    • 1
    Email author
  1. 1.Department of Pharmacology, Poona College of PharmacyBharati Vidyapeeth Deemed UniversityPuneIndia

Personalised recommendations