Skip to main content

Advertisement

SpringerLink
Log in

Protective Effects of Lithium on Acetic Acid-Induced Colitis in Rats

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Inflammatory bowel disease (IBD) is a multifactorial disease with unknown etiology characterized by oxidative stress, leukocyte infiltration, and rise in inflammatory cytokines such as tumor necrosis factor (TNF-α). Lithium, as a therapeutic agent for bipolar disorder, exerts some anti-inflammatory properties. In this study we have investigated the effects of lithium on acetic-acid-induced colitis in rats. Lithium (5, 10, and 20 mg/kg) was administered 1 h before the introduction of acetic acid. Colonic status was investigated 24 h following colitis induction through macroscopic, histological, and biochemical analyses. Lithium (20 mg/kg) ameliorated macroscopic and microscopic scores. These observations were accompanied by a reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malondialdehyde content in inflamed colon as well as a decrease in TNF-α levels. These findings suggest that lithium exerts beneficial effects on experimental colitis and therefore might be useful in the treatment of IBD.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Brown SJ, Mayer L. The immune response in inflammatory bowel disease. Am J Gastroenterol. 2007;102:2058–2069.

    Article  PubMed  CAS  Google Scholar 

  2. Papadakis KA, Targan SR. Role of cytokines in the pathogenesis of inflammatory bowel disease. Annu Rev Med. 2000;51:289–298.

    Article  PubMed  CAS  Google Scholar 

  3. Barnes PJ. Nuclear factor-kappa B. Int J Biochem Cell Biol. 1997;29(6):867–870.

    Article  PubMed  CAS  Google Scholar 

  4. Cross RK, Wilson KT. Nitric oxide in inflammatory bowel disease. Inflamm Bowel Dis. 2003;9(3):179–189.

    Article  PubMed  Google Scholar 

  5. Szanto I, Rubbia-Brandt L, Kiss P, et al. Expression of NOX1, a superoxide-generating NADPH oxidase, in colon cancer and inflammatory bowel disease. J Pathol. 2005;207:164–176.

    Article  PubMed  CAS  Google Scholar 

  6. Krieglstein CF, Cerwinka WH, Laroux FS, et al. Regulation of murine intestinal inflammation by reactive metabolites of oxygen and nitrogen: divergent roles of superoxide and nitric oxide. J Exp Med. 2000;194(9):1207–1218.

    Article  Google Scholar 

  7. Goodwin FK, Jamison KR. Manic-Depressive Illness. New York: Oxford University Press; 1990.

    Google Scholar 

  8. Ebstein RP, Hermoni M, Belmaker RH. The effect of lithium on noradrenalineinduced cyclic AMP accumulation in rat brain: inhibition after chronic treatment and absence of supersensitivity. J Pharmacol Exp Ther. 1980;213(1):161–167.

    PubMed  CAS  Google Scholar 

  9. Oppenheim G, Ebstein RP, Belmaker RH. Effect of lithium on the physostigmine-induced behavioral syndrome and plasma cyclic GMP. J Psychiatr Res. 1979;15:133–138.

    Article  PubMed  CAS  Google Scholar 

  10. Harvey BH, Carstens ME, Taljaard JJ. Evidence that lithium induces a glutamatergic nitric oxide mediated response in rat brain. Neurochem Res. 1994;19:469–474.

    Google Scholar 

  11. Rapaport MH, Manji HK. The effects of lithium on ex vivo cytokine production. Biol Psychiat. 2001;50:217–224.

    Article  PubMed  CAS  Google Scholar 

  12. Schwabe RF, Brenner DA. Role of glycogen synthase kinase-3 in TNF-alpha-induced NF-kappaB activation and apoptosis in hepatocytes. Am J Physiol Gastrointest Liver Physiol. 2002;283(1):G204–G211.

    PubMed  CAS  Google Scholar 

  13. MacPherson BR, Pfeiffer CJ. Experimental production of diffuse colitis in rats. Digestion. 1978;17:135–150.

    Article  PubMed  CAS  Google Scholar 

  14. Antonioli L, Fornai L, Colucci R, et al. Inhibition of adenosine deaminase attenuates inflammation in experimental colitis. J Pharmacol Exp Ther. 2007;322:435–442.

    Article  PubMed  CAS  Google Scholar 

  15. Nakase H, Okazaki K, Tabata Y, et al. An oral drug delivery system targeting immuneregulating cells ameliorates mucosal injury in trinitrobenzene sulfonic acidinduced colitis. J Pharmacol Exp Ther. 2001;297:1122–1128.

    PubMed  CAS  Google Scholar 

  16. Morris GP, Beck PL, Herridge MS, Depew WT, Szewezuk MR, Wallace JL. Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology. 1989;96:795–803.

    PubMed  CAS  Google Scholar 

  17. Appleyard CB, Wallace JL. Reactivation of hapten-induced colitis and its prevention by anti-inflammatory drugs. Am J Physiol. 1995;269:G119–G125.

    PubMed  CAS  Google Scholar 

  18. Mullane KM, Kremer R, Smith B. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J Pharmacol Methods. 1985;14:157–167.

    Article  PubMed  CAS  Google Scholar 

  19. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–358.

    Article  PubMed  CAS  Google Scholar 

  20. Reinecker HC, Steffen M, Witthoeft T, Pflueger I, Schreibe S, Mac-Dermatt RP, Raedler A. Enhanced secretion of tumor necrosis factor-alpha, IL-6 and IL-1 beta by isolated lamina propria mononuclear cells from patients with ulcerative colitis and crohn’s disease. Clin Exp Immunol. 1993;94:174–181.

    Google Scholar 

  21. Dehpour AR, Sadr SS, Nouroddini M, et al. Comparison of simultaneous administration of lithium with l-NAME or l-arginine on morphine withdrawal syndrome in mice. Hum Psychopharmacol Clin Exp. 2000;15:87–93.

    Article  Google Scholar 

  22. Reus VL. Mental disorders. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, eds. Harrison’s Principles of Internal Medicine. New York: McGraw-Hill; 2005:2547–2561.

  23. Elson CO, Sartor RB, Tennyson GS, Riddell RH. Experimental models of inflammatory bowel disease. Gastroenterology. 1995;109:1344–1367.

    Article  PubMed  CAS  Google Scholar 

  24. Rogler G. Update in inflammatory bowel disease pathogenesis. Curr Opin Gastroenterol. 2004;20:311–317.

    Article  PubMed  Google Scholar 

  25. Kruidenier L, Kuiper I, Lamers CB. Intestinal oxidative damage in inflammatory bowel disease: semi-quantification, localization, and association with mucosal antioxidants. J Pathol. 2003;201:28–36.

    Article  PubMed  CAS  Google Scholar 

  26. Yoshida N, Yoshikawa T, Yamaguchi T, et al. A novel water-soluble vitamin E derivative protects against experimental colitis in rats. Antiox Redox Signal. 1999;4:555–562.

    Google Scholar 

  27. Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1987;1:441–445.

    PubMed  CAS  Google Scholar 

  28. Dagli U, Balk M, Yucel D. The role of reactive oxygen metabolites in ulcerative colitis. Inflamm Bowel Dis. 1997;3(4):260–264.

    Article  Google Scholar 

  29. Koch TR, Yuan LX, Stryker SJ. Total antioxidant capacity of colon in patients with chronic ulcerative colitis. Dig Dis Sci. 2000;45(9):1814–1819.

    Article  PubMed  CAS  Google Scholar 

  30. Bhaskar L, Ramakrishna BS, Balasubramanian KA. Colonic mucosal antioxidant enzymes and lipid peroxide levels in normal subjects and patients with ulcerative colitis. J Gastroent Hepatol. 1997;10:140–143.

    Google Scholar 

  31. Stucchi AF, Shofer S, Leeman S. NK-1antagonist reduces colonic inflammation and oxidative stress in dextran sulfate-induced colitis in rats. Am J Physiol Gastrointest Liver Physiol. 2000;279:G1298–G1306.

    PubMed  CAS  Google Scholar 

  32. Newberry RD, Stenson WF, Lorenz RG. Cyclooxygenase-2 dependent arachidonic acid metabolites are essential modulators of the intestinal immune response to dietary antigen. Nat Med. 1999;5:900–906.

    Article  PubMed  CAS  Google Scholar 

  33. Hagar HH, Medany AE, Eter EE, Arafa M. Ameliorative effects of pyrrolidinedithiocarbamate on acetic acid-induced colitis in rats. Eur J Pharmacol. 2007;554:69–77.

    Article  PubMed  CAS  Google Scholar 

  34. Lieb J. Lithium and immune function. Med Hypotheses. 1987;23:73–93.

    Article  PubMed  CAS  Google Scholar 

  35. Gallicchio VS, Hughes NK, Tse KF, Ling J, Birch NJ. Effect of lithium in immunodeficiency: improved blood cell formation in mice with decreased hematopoiesis as the result of LP-BM5 MuL V infection. Antiviral Res. 1995;26:189–202.

    Article  PubMed  CAS  Google Scholar 

  36. Lenz SP, Izui S, Benediktsson H, Hart DA. Lithium chloride enhances survival of NZB/W lupus mice: influence of melatonin and timing of treatment. Int J Immunopharmacol. 1995;17:581–592.

    Article  PubMed  CAS  Google Scholar 

  37. Lenz SP, Pak C, Hart DA. Low dose LiCl treatment enhances survival and inhibits pancreatic beta cell destruction in the NOD model of type I diabetes. Lithium. 1994;5:139–146.

    CAS  Google Scholar 

  38. Fillmann H, Kretzmann NA, San-Miguel B, et al. Glutamine inhibits over-expression of pro-inflammatory genes and down-regulates the nuclear factor kappaB pathway in an experimental model of colitis in the rat. Toxicology. 2007;236:217–226.

    Article  PubMed  CAS  Google Scholar 

  39. Martínez-Flores S, Gutiérrez-Fernández B, Sánchez-Campos S, González-Gallego J, Tuñón MJ. Quercetin prevents nitric oxide production and nuclear factor kappa B activation in interleukin-1b-activated rat hepatocytes. J Nutr. 2005;135:1359–1365.

    Google Scholar 

  40. García-Mediavilla MV, Crespo I, Collado PS, Esteller A, Sánchez-Campos S, Tuñón MJ, González-Gallego J. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol. 2007;557:221–229.

    Google Scholar 

  41. Ardite E, Panes J, Miranda M, et al. Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease. Br J Pharmacol. 1998;124:431–433.

    Article  PubMed  CAS  Google Scholar 

  42. Elson CO. The basis of current and future therapy for inflammatory bowel disease. Am J Med. 1996;100(6):656–662.

    Article  PubMed  CAS  Google Scholar 

  43. Dohi T, Fujihashi K, Rennert PD, Iwatani K, Kiyono H, McGhee JR. Hapten-induced colitis is associated with colonic patch hypertrophy and T helper cell 2-type responses. J Exp Med. 1999;189:1169–1179.

    Article  PubMed  CAS  Google Scholar 

  44. Zheng L, Gao ZQ. Wang SX. A chronic ulcerative colitis model in rats. World J Gastroenterol. 2000;6(1):150–152.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran

    Ali Daneshmand, Reza Rahimian, Hamed Mohammadi, Shahram Ejtemaee-Mehr, Roohollah Babaei Kelishomi & Ahamd Reza Dehpour

  2. Endocrinology and Metabolism Research Centre, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Tavangar

  3. Department of Pathology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Seyed Mohammad Tavangar

Authors
  1. Ali Daneshmand
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Reza Rahimian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hamed Mohammadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Shahram Ejtemaee-Mehr
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Seyed Mohammad Tavangar
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Roohollah Babaei Kelishomi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ahamd Reza Dehpour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahamd Reza Dehpour.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Daneshmand, A., Rahimian, R., Mohammadi, H. et al. Protective Effects of Lithium on Acetic Acid-Induced Colitis in Rats. Dig Dis Sci 54, 1901–1907 (2009). https://doi.org/10.1007/s10620-008-0569-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-008-0569-3

Keywords

Search

Navigation