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Effects of dexfenfluramine on serotonin levels of mice ileum, contractility, glutathione and malondialdehyde level

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Abstract

Dexfenfluramine is one of the anorectic drugs that suppresses food intake which acts via inhibition of reuptake of serotonin into brain terminal. Gastrointestinal tract is the main source of peripheral serotonin which is involved in the regulation of gastrointestinal motility. During the use of anorectic drugs, the antioxidant defence is affected especially by reactive oxygen species.

The purpose of this study to search: The effect of dexfenfluramine on serotonin levels of ileum and the effect of dexfenfluramine on ileal contractility and oxidative stress.

Materials and Methods: Twenty-two adult male Swiss-albino mice were divided two groups (1) Control, (2) Dexfenfluramine treated (i.p. twice a day 0.2 mg kg−1 in 0.2 ml saline solution for 7 days). Animal body weights were recorded at the beginning and at the end of the experimental period. Ileum tissues contractile responses to different concentrations of KCl and acethycholine were recorded on polygraph. In the meantime ileal tissue malondialdehyde, a product of lipid peroxidation, and glutathione, endogenous antioxidant levels were assessed by spectrophotometric methods. Ileal tissue serotonin level determined by immunohistochemical method. Body weights decrease and ileal contractile response of acethycholine increased significantly by dexfenfluramine treatment. Meanwhile, ileum glutathione levels decreased and malondialdehyde levels increased in dexfenfluramine treated group. Immunohistochemical detection showed that ileal serotonin levels increased by dexfenfluramine treatments.

As a conclusion, there is a relationship between increased ileal contractility and oxidant status in dexfenfluramine treated animals. These effects can be related by increased serotonin levels which is induced by dexfenfluramine in ileum. (Mol Cell Biochem xxx: 151–157, 2005)

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References

  1. O'Meara S, Riemsma R, Shirran L, Mather L, ter Riet G: A repid and systematic review of the clinical effectiveness and cost-effectives of orlistat in the management of obesity. Health Technal Assess 5(18): 1–81, 2001

    Google Scholar 

  2. Michelakis E: Anorectic drugs and vascular disease: the role of voltage-gated K+ channels. Vascul Pharmacol 38(1): 51–59, 2002

    Article  PubMed  CAS  Google Scholar 

  3. Kristine A, Perry B, Perry P: Dexfenfluramine hydrochloride: an anorexigenic agent. Am J Health-Syst Pharm 54(15): 2059–2072, 1997

    Google Scholar 

  4. Leibowitz SF, Shor-Posner G: Brain serotonin and eating behaviour. Appetite 7 (Suppl): 1–14, 1986

    PubMed  CAS  Google Scholar 

  5. Mc Cormack JG, Dean HG, Jennings GJ, Blundell JE: Effects of chronic low doses of d-Fenfluramine on weight gain and calorie intake, brown adipose tissue thermogenic parameters and brain neurotransmitter content in rats fed chow or palatable diet. In J Obes 13: 625–633, 1989

    CAS  Google Scholar 

  6. Bubenik GA, Ball RO, Pang SF: The effect of rood deprivation on brain and gastrointestinal tissue levels of tryptophan, serotonin, 5-hydroxyindoleacetic acid and melotonin. J Pineal Res 7–16, 1992

  7. Rother BA, Prelusky DB, Thomoson BK: The role of tryptophan in don-induced feed rejection. J Environ Sci Health 31(6): 1279–1288, 1996

    Google Scholar 

  8. Meyer T, Brinck U: Differential distribution of serotonin and tryptophan hydroxylase in the human gastrointestinal tract. Digestion 60(1): 63–68, 1999

    Article  PubMed  CAS  Google Scholar 

  9. Noguchi T, Nishino M, Kido R: Tryptophan 5-hydroxylase in rat intestine. Biochem J 131: 375–380, 1973

    PubMed  CAS  Google Scholar 

  10. Read NW, Gwee KA: The importance of 5-hyroxytryptamine receptors in the gut. Pharmacol Ther Apr–May 62 (1–2): 159–173, 1994

    CAS  Google Scholar 

  11. Yamamato I, Kuwahara A, Fujimura M, Kadowaki M, Fujimiya M: Involvement of 5-HT3 and 5-HT4 receptors in the motor activity of isolated vascularly perfused rat duodenum. Neurogastroenterol Motil Dec 11(6): 457–465, 1999

    Google Scholar 

  12. Hopkinson GB, Hinsdale J, Jaffe BM: Contraction of canine stomach and small bowel by intravenous administration of serotonin. Scand J Gastroenterol 24: 923–932, 1989

    PubMed  CAS  Google Scholar 

  13. Bennett MR: The concept of transmitter receptors: 100 years on. Neuropharmacology 39: 523–546, 2000

    Article  PubMed  CAS  Google Scholar 

  14. Sabeur G: Effect of temparature on the contractile response of isolated rat small intestine to acetlycholine and KCl: calcium dependence. Arch Physiol Biochem 104(2): 220–228, 1996

    Article  PubMed  CAS  Google Scholar 

  15. Boschmann M, Frenz U, Murphy CM: Changes in energy metabolizm and metabolite patterns of obese rats after application of dexfenfluramine. Pharmacol Biochem Behav 53(3): 549–558, 1996

    Article  PubMed  CAS  Google Scholar 

  16. Gershon MD: Serotonin: its role and receptors in enteric neurotransmission. Adv Exp Med Biol 294: 221–230, 1991

    PubMed  CAS  Google Scholar 

  17. Almeida VD, Camarini R, Azzalis LA, Jungueria VBC, Carlini EA: Chronic fenfluramine treatment of rats with different ages: effects on brain oxidative stress-related parameters. J Biochem Toxicology 11(4): 197–201, 1996

    Google Scholar 

  18. Babior BM : Superoxide: a two-edged sword. Braz J Med Biol Res 30: 141–155, 1997

    Article  PubMed  CAS  Google Scholar 

  19. Rothman RB, Baumann MH: Serotonin releasing agents Neurochemical, therapeutic and adverse effects. Pharmacol Biochem Behav 71: 825–836, 2002

    Article  PubMed  CAS  Google Scholar 

  20. Casini A, Ferrali M, Pompelam A, Maellaro A, Comborti M: Lipid peroxidation and cellular damage in extrahepatic tissues of bromobenzene intoxicated mice. Am J Pathol 123: 520–531, 1986

    PubMed  CAS  Google Scholar 

  21. Aykaç G, Uysal M, Yalçı n AS, Koçak-Toker N, Sivas A, Öz H: The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36: 71–76, 1985

    PubMed  Google Scholar 

  22. Balcı oglu A, Wurtman RJ: Effects of fenfluramine and phentermine (fenphen) on dopamine and serotonin release in rats striatum: In vivo microdialysis study in conscious animals. Brain Res 813: 67–72, 1998

    PubMed  Google Scholar 

  23. Rowland NE, Roth JD, McMullen MR, Patel A, Cespedes AT: Dexfenfluramine and norfenfluramine: comparison of mechanism of action in feeding and brain Fos-ir studies. Am J Physiol Regul Integr Comp Physiol 278: R390–399, 2000

    PubMed  CAS  Google Scholar 

  24. Wellman PJ, Jones SL, Miller DK: Effects of preexposure to dexfenfluramine, phentermine, dexfenfluramine-phentermine or fluoxetine on sibutramine-induced hypophagia in the adult rat. Pharmacol Biochem Behav 75: 103–114, 2003

    Article  PubMed  CAS  Google Scholar 

  25. Wilding JPH, Gilbey SG, Jones PM, Mannan MM, Ghatei MA, Bloom SR: Dexfenfluramine treatment and hypothalamic neuropeptides in diet – induced obesity in rats. Peptides 13: 557–563, 1992

    Article  PubMed  CAS  Google Scholar 

  26. Taniyama K, Makimato N, Furuichi A, Sakurai-Yamashita Y, Nagase Y, Kaibara M, Kanematsu T: Functions of peripheral 5-hydroxy-tryptamine 4 receptor in gastrointestinal motility. J Gastroenterol 35(8): 575–582, 2000

    Article  PubMed  CAS  Google Scholar 

  27. Salvador MT, Murillo MD, Rodriguez-Yoldi MC, Alcalde AI, Mesonero JE, Rodriguez-Yoldi M: Effect of serotonin on the physiology of the rabbit small intestine. Can J Physiol Pharmacol 78: 359–366, 2000

    Article  PubMed  CAS  Google Scholar 

  28. Wardle KA, Sanger GJ: The guinea-pig distal colon a sensitive preparation for the investigation of 5-HT4 receptor mediated contractions. Br J Pharmacol 110:1593–1599, 1993

    PubMed  CAS  Google Scholar 

  29. Tuladhar BR, Kaisar M, Naylor RJ: Evidence for a 5-HT3 receptor involvement in the facilitation of peristalsis on mucosal application of 5-HT in the guinea pig isolated ileum. Br J Pharmacol 122: 1174–1178, 1997

    Article  PubMed  CAS  Google Scholar 

  30. Lee YM, Chen HR, Hsiao G, Sheu JR, Wang JJ, Yen MH: Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. J Pineal Res 33: 72–80, 2002

    Article  PubMed  CAS  Google Scholar 

  31. Lee SH, Wang WW, Fanburg BL: Superoxide as an intermediate signal for serotonin-induced mitogenesis. Free Rad Biol Med 24(5): 855–858, 1998

    Article  PubMed  Google Scholar 

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Correspondence to Çiüdem Özer.

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Özer, Ç., Gönül, B., Elmas, Ç. et al. Effects of dexfenfluramine on serotonin levels of mice ileum, contractility, glutathione and malondialdehyde level. Mol Cell Biochem 280, 151–157 (2005). https://doi.org/10.1007/s11010-005-8842-7

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  • DOI: https://doi.org/10.1007/s11010-005-8842-7

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