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The effect of sodium valproate on acetic acid-induced colitis in rats

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Abstract

Ulcerative colitis is a chronic recurrent disease with incomplete treatment options. The current article evaluated the effect of sodium valproate on acetic acid-induced ulcerative colitis in rats. Rats were randomly distributed into six groups including Sham group, colitis control group, sodium valproate treatment groups (50, 100 and 300 mg/kg, i.p.) and dexamethasone-treatment group. Dexamethasone was used as a reference drug. Colitis was induced by intracolonic instillation of 2 mL of 3% acetic acid solution. The efficacy of sodium valproate was evaluated by macroscopical and histopathological scoring systems, hematocrit measurement as well as biochemical analysis including myeloperoxidase (MPO) and pro-inflammatory cytokines assessment. Sodium valproate, particularly with doses of 100 and 300 mg/kg significantly improved weight loss, and macroscopic damage, reduced ulcer area, colon weight, microscopic colitis index and elevated hematocrit level. Biochemical experiments showed elevated levels of colonic MPO activity, interleukin 1β (IL-1β), interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in colitis control group. Treatment with sodium valproate at the doses of 100 and 300 mg/Kg) decreased the MPO activity and colonic concentrations of IL-1β, IL-6 and TNF-α. The results provide evidence that sodium valproate has a protective effect in acetic acid-induced ulcerative colitis which might be due to its anti-inflammatory activities, and it may be useful in patients with ulcerative colitis.

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References

  • Baeuerle P, Henkel T (1994) Function and activation of NF-B in the immune system. Annu Rev Immunol 12:141–179

    Article  CAS  PubMed  Google Scholar 

  • Blanchard F, Chipoy C (2005) Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov Today 10:197–204

    Article  CAS  PubMed  Google Scholar 

  • Bosetti F, Weerasinghe GR, Rosenberger TA, Rapoport SI (2003) Valproic acid down-regulates the conversion of arachidonic acid to eicosanoids via cyclooxygenase-1 and-2 in rat brain. J Neurochem 85:690–696

    Article  CAS  PubMed  Google Scholar 

  • Bradley PP, Priebat DA, Christensen RD, Rothstein G (1982) Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 78:206–209

    Article  CAS  PubMed  Google Scholar 

  • Cardinale JP, Sriramula S, Pariaut R, Guggilam A, Mariappan N, Elks CM, Francis J (2010) HDAC inhibition attenuates inflammatory, hypertrophic, and hypertensive responses in spontaneously hypertensive rats. Hypertension 56:437–444

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Davis LL, Ryan W, Adinoff B, Petty F (2000) Comprehensive review of the psychiatric uses of valproate. J Clin Psychopharmacol 20:1–17

    Article  Google Scholar 

  • Dieleman LA, Palmen M, Akol H, Bloemena A, Pen A, Meuwissen SGM, Van Rees EP (1998) Chronic experimental colitis induced by dextran sulphate sodium (DSS) is characterized by Th1 and Th2 cytokines. Clin Exp Immunol 114:385–391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong W-G, Mei Q, Yu J-P, Xu J-M, Xiang L, Xu Y (2003) Effects of melatonin on the expression of iNOS and COX-2 in rat models of colitis. World J Gastroenterol 9:1307–1311

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  • Gelbmann CM (2000) Prediction of treatment refractoriness in ulcerative colitis and Crohn’s disease-do we have reliable markers? Inflamm Bowel Dis 6:123–131

    Article  CAS  PubMed  Google Scholar 

  • Halili MA, Andrews MR, Sweet MJ, Fairlie DP (2009) Histone deacetylase inhibitors in inflammatory disease. Curr Top Med Chem 9:309–319

    Article  CAS  PubMed  Google Scholar 

  • He J, Liang J, Zhu S, Zhao W, Zhang Y, Sun W (2011) Protective effect of taurohyodeoxycholic acid from Pulvis Fellis Suis on trinitrobenzene sulfonic acid induced ulcerative colitis in mice. Eur J Pharmacol 670:229–235

    Article  CAS  PubMed  Google Scholar 

  • Henry TR (2002) The history of valproate in clinical neuroscience. Psychopharmacol Bull 37:5–16

    Google Scholar 

  • Herias M, Koninkx J, Vos J, In’t Veld JH, Van Dijk J (2005) Probiotic effects of Lactobacillus casei on DSS-induced ulcerative colitis in mice. Int J Food Microbiol 103:143–155

    Article  CAS  PubMed  Google Scholar 

  • Hoesel B, Schmid JA (2013) The complexity of NF-κB signaling in inflammation and cancer. Mol Cancer 12:1

    Article  Google Scholar 

  • Ichiyama T, Okada K, Lipton JM, Matsubara T, Hayashi T, Furukawa S (2000) Sodium valproate inhibits production of TNF-α and IL-6 and activation of NF-κB. Brain Res 857:246–251

    Article  CAS  PubMed  Google Scholar 

  • Johannessen CU, Johannessen SI (2003) Valproate: past, present, and future. CNS Drug Rev 9:199–216

    Article  CAS  PubMed  Google Scholar 

  • Kankaanranta H et al (2010) Histone deacetylase inhibitors induce apoptosis in human eosinophils and neutrophils. J Inflamm 7:1–15

    Article  Google Scholar 

  • Karmeli F, Cohen P, Rachmilewitz D (2000) Cyclo-oxygenase-2 inhibitors ameliorate the severity of experimental colitis in rats. Eur J Gastroenterol Hepatol 12:223–231

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Nagao A, Terao J, Osawa T (2003) Inhibition of myeloperoxidase-catalyzed tyrosylation by phenolic antioxidants in vitro. Biosci Biotechnol Biochem 67:1136–1139

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Rowe M, Ren M, Hong JS, Chen PS, Chuang DM (2007) Histone deacetylase inhibitors exhibit anti-inflammatory and neuroprotective effects in a rat permanent ischemic model of stroke: multiple mechanisms of action. J Pharmacol Exp Ther 321:892–901

    Article  CAS  PubMed  Google Scholar 

  • Lampinen M et al (2005) Eosinophil granulocytes are activated during the remission phase of ulcerative colitis. Gut 54:1714–1720

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Shimoyama T, Suzuki K, Umeda T, Nakaji S, Sugawara K (2001) Effect of sodium butyrate on reactive oxygen species generation by human neutrophils. Scand J Gastroenterol 36:744–750

    Article  CAS  PubMed  Google Scholar 

  • MacPherson B, Pfeiffer C (1978) Experimental production of diffuse colitis in rats. Digestion 17:135–150

    Article  CAS  PubMed  Google Scholar 

  • Maeda S et al (2005) Nod2 mutation in Crohn’s disease potentiates NF-kappaB activity and IL-1beta processing. Science 307:734–738

    Article  CAS  PubMed  Google Scholar 

  • Millar A et al (1996) Evaluating the antioxidant potential of new treatments for inflammatory bowel disease using a rat model of colitis. Gut 39:407–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Minaiyan M, Hajhashemi V, Rabbani M, Fattahian E, Mahzouni P (2015) Evaluation of anti-colitic effect of fluvoxamine against acetic acid-induced colitis in normal and reserpinized depressed rats. Eur J Pharmacol 746:293–300

    Article  CAS  PubMed  Google Scholar 

  • Motaghi E, Hajhashemi V, Mahzouni P, Minaiyan M (2016) The effect of memantine on trinitrobenzene sulfonic acid-induced ulcerative colitis in mice. Eur J Pharmacol. doi:10.1016/j.ejphar.2016.10.032 (in press)

    PubMed  Google Scholar 

  • Motavallian A, Minaiyan M, Rabbani M, Andalib S, Mahzouni P (2012) Involvement of 5HT3 receptors in anti-inflammatory effects of tropisetron on experimental TNBS-induced colitis in rat. Bioimpacts 3:169–176

    Google Scholar 

  • Motavallian-Naeini A, Minaiyan M, Rabbani M, Mahzuni P (2012) Anti-inflammatory effect of ondansetron through 5-HT3 receptors on TNBS-induced colitis in rat. EXCLI 11:30–44

    Google Scholar 

  • Packey C, Sartor RB (2008) Interplay of commensal and pathogenic bacteria, genetic mutations, and immunoregulatory defects in the pathogenesis of inflammatory bowel diseases. J Intern Med 263:597–606

    Article  CAS  PubMed  Google Scholar 

  • Pervin M, Hasnat MA, Lim J-H, Lee Y-M, Kim EO, Um B-H, Lim BO (2016) Preventive and therapeutic effects of blueberry (Vaccinium corymbosum) extract against DSS-induced ulcerative colitis by regulation of antioxidant and inflammatory mediators. J Nutr Biochem 28:103–113

    Article  CAS  PubMed  Google Scholar 

  • Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276:36734–36741

    Article  CAS  PubMed  Google Scholar 

  • Raza M, Dhariwal MA, Ageel AM, Qureshi S (1996) Evaluation of the antiinflammatory activity of sodium valproate in rats and mice. Gen Pharmacol 27:1395–1400

    Article  CAS  PubMed  Google Scholar 

  • Roderburg C et al (2011) Micro RNA profiling reveals a role for miR 29 in human and murine liver fibrosis. Hepatology 53:209–218

    Article  CAS  PubMed  Google Scholar 

  • Schwertheim S, Worm K, Schmid K, Sheu-Grabellus S (2014) Valproic acid downregulates NF-κB p50 activity and IRAK-1 in a progressive thyroid carcinoma cell line. Horm Metab Res 46:181–186

    Article  CAS  PubMed  Google Scholar 

  • Shang Y, Jiang YX, Ding ZJ, Shen AL, Xu SP, Yuan SY, Yao SL (2010) Valproic acid attenuates the multiple-organ dysfunction in a rat model of septic shock. Chin Med J 123:2682–2687

    CAS  PubMed  Google Scholar 

  • Shiah IS, Yatham LN, Yeh CB, Ravindran AV (2005) Effect of valproate on plasma levels of interleukin-6 in healthy male humans. Int Clin Psychopharmacol 20:295–298

    Article  PubMed  Google Scholar 

  • Tanaka T et al (2008) In patients with ulcerative colitis, adsorptive depletion of granulocytes and monocytes impacts mucosal level of neutrophils and clinically is most effective in steroid naïve patients. Dig Liver Dis 40:731–736

    Article  CAS  PubMed  Google Scholar 

  • Ten Hove T et al (2001) Blockade of endogenous IL-18 ameliorates TNBS-induced colitis by decreasing local TNF-α production in mice. Gastroenterology 121:1372–1379

    Article  PubMed  Google Scholar 

  • Thoreson R, Cullen JJ (2007) Pathophysiology of inflammatory bowel disease: an overview. Surg Clin North Am 87:575–585

    Article  PubMed  Google Scholar 

  • Ximenes JCM et al (2013) Valproic acid: an anticonvulsant drug with potent antinociceptive and anti-inflammatory properties. Naunyn Schmiedebergs Arch Pharmacol 386:575–587

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Zhang Z, Fauser U, Schluesener H (2008) Valproic acid attenuates inflammation in experimental autoimmune neuritis. Cell Mol Life Sci 24:4055–4065

    Article  Google Scholar 

  • Zhang Y, Cardell L-O, Edvinsson L, Xu C-B (2013) MAPK/NF-κB-dependent upregulation of kinin receptors mediates airway hyperreactivity: a new perspective for the treatment. Pharmacol Res 71:9–18

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Financial support for this study was received from School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. (Grant Number: 384589).

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Authors and Affiliations

  1. Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Ali Najafi, Ehsan Motaghi & Mohammad Javad Hosseini

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

    Ehsan Motaghi

  3. Department of Immunology, Shahrekord University of Medical Science, Shahrekord, Iran

    Masoumeh Ghasemi-Pirbaluti

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  1. Ali Najafi
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  2. Ehsan Motaghi
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  3. Mohammad Javad Hosseini
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  4. Masoumeh Ghasemi-Pirbaluti
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Correspondence to Ehsan Motaghi.

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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted.

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Najafi, A., Motaghi, E., Hosseini, M.J. et al. The effect of sodium valproate on acetic acid-induced colitis in rats. Inflammopharmacol 25, 137–145 (2017). https://doi.org/10.1007/s10787-016-0304-1

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