Skip to main content
SpringerLink
Log in

Cold-restraint- and TRH-induced ulcer models demonstrate different biochemical and morphological manifestations in gastric and hepatic tissues in rats

Role of calcitonin

  • Esophageal, Gastric, and Duodenal Disorders
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

In the present study, two ulcer models—central thyrotropin-releasing hormone (TRH) injection and cold-restraint stress (CRS) application—were compared. Animals were treated either with salmon calcitonin (sCT) or saline intracerebroventricularly (ICV) before CRS exposure or ICV TRH injection. In both models, besides ultrastructural properties, ulcer indexes and lipid peroxidation (LP) and glutathione (GSH) levels of liver and stomach were determined. While TRH treatment did not affect GSH and LP levels of the stomach and led to a slight decrease in hepatic GSH levels. CRS induced a marked reduction in gastric and hepatic GSH and an increase in LP levels of both tissues. sCT pretreatment prevented the reduction of gastric and hepatic GSH levels and morphological damage of both tissues in the CRS group. However, the same treatment did not prevent the TRH-induced reduction of hepatic GSH levels and, interestingly, it worsened the ultrastructural disturbances in the liver. Although sCT prevented macroscopic ulcer formation in both models, it did not totally reverse the microscopic effects of TRH.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Takagi K, Kasuya Y, Watanabe K: Studies on the drugs for peptic ulcer: A reliable method for producing stress ulcer in rats. Chem Pharmacol Bull 12:456–472, 1964

    Google Scholar 

  2. Goto Y, Tache Y: Gastric erosions induced by intracisternal injection of thyrotropin releasing hormone (TRH). Peptides 61:153–156, 1985

    Google Scholar 

  3. Tache Y, Kolue E, Hagiwara MM, Kauffman G: Central nervous system action of calcitonin to alter experimental gastric ulcers in rats. Gastroenterology 94:145–150, 1988

    Google Scholar 

  4. Morley JE, Levine AS, Siluis SE: Intraventricular calcitonin inhibits gastric asid seeretion. Science 214:671–673, 1981

    Google Scholar 

  5. Guth PH, Kozbur X: Pathogenesis of gastric microcirculatory and mast cell changes in restraint stress. Am J Dig Dis 13:530–535, 1968

    Google Scholar 

  6. Guth PH: Gastric blood flow in restraint stress. Am J Dig Dis 17:807–813, 1972

    Google Scholar 

  7. Hemmer J, Hofmann W: Effect of cimetidine upon gastric secretion and mucosal blood flow in rat stressed by restraint. Res Exp Med 176:207–217, 1980

    Google Scholar 

  8. Garrick T, Buack S, Bass P: Gastric motility is a major factor in cold restraint-induced lesion formation in rats. Am J Physiol 250:G191-G199, 1986

    Google Scholar 

  9. Yeĝen B, Dedeoĝlu A, Aykaç I, Oktay S, Yalçin AS: Effects of cold-restraint stress on glutathione and lipid peroxidation in the liver and glandular stomach of rats. Pharmacol Res 22:45–48, 1990

    Google Scholar 

  10. Maeda-Hagiwara M, Watanabe H, Kanaoka R, Watanaber K: Effects of calcitonin in the gastric mucosa in the rat.In New Pharmacology of Ulcer Disease: Experimental and New Therapeutic Approaches. S Szabo, G Mozsic (eds). Boston, Praeger, 1977, pp 395–403

    Google Scholar 

  11. Bueno L, Ferre JP, Fioramonti J, Honde C: Effects of intracerobroventricular administration of neurotensin, substance P and calcitonin on gastrointestinal motility in normal and vagotomized rats. Regul Pept 6:197–205, 1983

    Google Scholar 

  12. Erin N, Atine N, Özkutlu U, Yalçin S, Oktay Ş: The effects of calcitonin on stress-induced gastric ulcers, glutathione and lipid peroxidation in rats. Marmara Med J 6:91–94, 1993

    Google Scholar 

  13. Arancibia S, Tabia-Arancibia L, Assenmacher I, Astier H: Direct evidence short term cold induced TRH release in the median eminence of unaesthetized rats. Neuroendocrinology 37:225–228, 1983

    Google Scholar 

  14. Tache Y, Stephens KL, Ishikawa T. Central nervous system action of TRH to influence gastrointestinal function and ulceration. Ann NY Acad Sci 553:269–285, 1989

    Google Scholar 

  15. Inoue M, Kinne R, Tran T, Arias IM: Glutathione transport across hepatocyte plasma membrane. Eur J Biochem 138:491–495, 1984

    Google Scholar 

  16. Hirota M, Inoue M, Ando Y, Hirayama K, Morino Y, Sakamoto K, Akagi M: Inhibition of stress induced injury in rat by glutathione. Gastroenterology 97:853–859, 1989

    Google Scholar 

  17. Poli G: Liver damage due to free radicals. Br Med Bull 49:604–620, 1993

    Google Scholar 

  18. Arai I, Muramatsu M, Aihara H: Effect of restrain and waterimmersion stress and insulin on gastric secretion in rats. Physiol Behav 40:357–361, 1987

    Google Scholar 

  19. Kreider MS, Engber TM, Nilaver G, Zimmermen EA, Winokur A: Immunohistochemical locolization of TRH in rat CNS: Comparison with RIA studies. Peptides 6:997–1000, 1985

    Google Scholar 

  20. Palkovits M, Mezey E, Eskay RL, Brownstein MJ: Innervation of the nucleus of the solitary tract and the dorsal vagal nucleus by thyrotropin-releasing hormone-containing raphe neurons. Brain Res 373:246–251, 1986

    Google Scholar 

  21. Rinaman L, Miselis RR: Thyrotropin-releasing hormone-immunoreactive nerve terminals synapse on the dentrites of gastric vagal motoneurons in the rat. J Comp Neurol 294:235–251, 1990

    Google Scholar 

  22. Garric T, Stephens R, Ishikawa T, Sierra A, Avidan A, Weiner H, Tache Y: Medullary sites for TRH analogue stimulation of gastric contractility in the rat. Am J Physiol 256:G1011-G1015, 1989

    Google Scholar 

  23. Ishikawa T, Yang H, Tache Y: Medullary sites for TRH analogue, RX 77368, to stimulate gastric acid secretion in the rat. Gastroenterology 95:1470–1476, 1988

    Google Scholar 

  24. Goto Y, Tache Y: Gastric erosions induced by thyrotropin-releasing hormone (TRH) in rats. Peptides 6:153–156, 1985

    Google Scholar 

  25. Maeda-Hagiwara M, Watanabe H: Intracerebroventricular injection of a TRH analogue, γ-butyrolactone-γ—carbonyl-l-histidyl-prolinamide, induces gastric lesions and gastric acid stimulation in rats. Naunyn-Schmiedebergs Arch Pharmacol 330:142–146, 1985

    Google Scholar 

  26. Kiraly A, Süto G, Livingston EH, Guth PH, Pierre S, Tache Y: Central vagal activation by TRH induces gastric hyperemia: role of CGPR in capsaicin sensitive afferents in rats. Am J Physiol 267(Gastrointest Liver Physiol 30):G1041-G1049, 1994

    Google Scholar 

  27. Zanelli JM, Stracca-Gasser M, Gaines-Das RE, Guidobono F: The short term effect of peripherally adminestered brain-gut peptides on gastric acid secretion in rats. Agents Actions 35:122–129, 1992

    Google Scholar 

  28. Raggenbass M, Vozzi C, Tribollet E, Dubois-Dauphin M, Dreifuss JJ: Thyrotropin-releasing hormone causes direct excitation of dorsal vagal and solitary tract neurons in rat brainstem slices. Brain Res 530:85–90, 1990

    Google Scholar 

  29. Ishigura T, Iguchi A, Kunoh Y, Goto M, Uemura K, Miura H, Nonogaki K, Sakamoto N: Relative contribution of nervous system and hormones to hyperglycemia induced by thyrotropin releasing hormone in fed rats. Neuroendocrinology 54:1–6, 1991

    Google Scholar 

  30. Maruhashi S, Kunii Y, Tominaga M: Modulation of plasma glucose levels by thyrotropin-releasing hormone administered intraventricularly in the rat. Neuroendocrinology 48:640–644, 1988

    Google Scholar 

  31. Kakkar P, Mehrotra S, Viswanathan PN: Interrelationship of active oxygen species, calcium dynamics and biomembrane functions as central mechanism in cytoxicity.In Biomembranes in Health and Disease, Vol 1. AM Kidwai, RK Upreti, PK Ray (eds). New Dehli, Today & Tomorrow's Printer and Publishers, 1990, pp 205–215

    Google Scholar 

  32. Mehrotra S, Kakkar P, Viswanathan PN: Mitocondrial damage by active oxygen species in vitro. Free Rad Biol Med 10:277–285, 1991

    Google Scholar 

  33. Brown MR: Thyrotropin releasing hormone: A putative CNS regulator of the autonomic nervous system. Dife Sci 28:1789–1795, 1981

    Google Scholar 

  34. Yamaguchi M: Stimulatory effect of calcitronin on calcium inflow in isolated rat hepatocytes. Mol Cell Endocrinol 75:65–70, 1991

    Google Scholar 

  35. Yamaguchi M, Williamson JR: Stimulatory effect of calcitonin on calcium uptake and glucose production in isolated rat hepatocytes. Horm Metal Res 15:176–180, 1983

    Google Scholar 

  36. Nelson EJ, Hinkle PM: Thyrotropin-releasing hormone activates Ca+2 efflux. J Biol Chem 269(49):30854–30860, 1994

    Google Scholar 

  37. Levine AS, Morley JE: Reduction of feeding in rats by calcitonin. Brain Res 222:187–191, 1981

    Google Scholar 

  38. Hiraishi H, Akira T, Ota S, Mutoh H, Sugimoto T, Razandi M, Ivey JK: Oxygen metabolites stimulates mucous glycoprotein secretion from cultured rat gastric mucous cells. Am J Physiol 261:G662-G668, 1991

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Histology, Marmara University School of Medicine, 81326, Haydarpaşa-Istanbul, Turkey

    Nuray Erin MD, Imer Okar MD, Şule Oktay MD, PhD, Feriha Ercan, Serap Arbak PhD & Berrak Ç. Yeĝen MD

  2. Department of Pharmacology, Marmara University School of Medicine, 81326, Haydarpaşa-Istanbul, Turkey

    Nuray Erin MD, Imer Okar MD, Şule Oktay MD, PhD, Feriha Ercan, Serap Arbak PhD & Berrak Ç. Yeĝen MD

  3. Department of Physiology, Marmara University School of Medicine, 81326, Haydarpaşa-Istanbul, Turkey

    Nuray Erin MD, Imer Okar MD, Şule Oktay MD, PhD, Feriha Ercan, Serap Arbak PhD & Berrak Ç. Yeĝen MD

Authors
  1. Nuray Erin MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Imer Okar MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Şule Oktay MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Feriha Ercan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Serap Arbak PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Berrak Ç. Yeĝen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Erin, N., Okar, I., Oktay, Ş. et al. Cold-restraint- and TRH-induced ulcer models demonstrate different biochemical and morphological manifestations in gastric and hepatic tissues in rats. Digest Dis Sci 41, 55–64 (1996). https://doi.org/10.1007/BF02208584

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02208584

Key Words

Search

Navigation