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Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats

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Abstract

Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK2/gastrin receptor antagonist) and ranitidine (histamine H2 receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and NG-nitro l-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine & Health Sciences, UAE University, P.O. Box-17666, Al Ain, United Arab Emirates

    S. I. Chandranath, S. M. A. Bastaki & A. Adem

  2. School of Forensic and Investigative Sciences, University of Central Lancashire, Preston, PR1 2HE, England, UK

    A. D’Souza & J. Singh

  3. School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, England, UK

    A. D’Souza & J. Singh

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  1. S. I. Chandranath
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  2. S. M. A. Bastaki
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  3. A. D’Souza
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  4. A. Adem
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  5. J. Singh
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Correspondence to J. Singh.

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Chandranath, S.I., Bastaki, S.M.A., D’Souza, A. et al. Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats. Mol Cell Biochem 349, 205–212 (2011). https://doi.org/10.1007/s11010-010-0675-3

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