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      In Vivo Models Used for Evaluation of Potential Antigastroduodenal Ulcer Agents

      1 , 2 , 1 , 3 , 4
      Ulcers
      Hindawi Limited

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          Abstract

          Peptic ulcer is among the most serious gastrointestinal diseases in the world. Several orthodox drugs are employed for the treatment of the disease. Although these drugs are effective, they produce many adverse effects thus limiting their use. In recent years, there has been a growing interest in alternative therapies, especially those from plants due to their perceived relative lower side effects, ease of accessibility, and affordability. Plant medicines with ethnomedicinal use in peptic ulcer management need to be screened for their effectiveness and possible isolation of lead compounds. This requires use of appropriate animal models of various ulcers. The limited number of antiulcer models for drug development against gastric and duodenal ulcer studies has hindered the progress of targeted therapy in this field. It is, therefore, necessary to review the literature on experimental models used to screen agents with potential antigastroduodenal ulcer activity and explain their biochemical basis in order to facilitate their use in the development of new preventive and curative antiulcer drugs. Clinical trials can then be carried out on agents/drugs that show promise. In this paper, current in vivo animal models of ulcers and the pathophysiological mechanisms underlying their induction, their limitations, as well as the challenges associated with their use have been discussed.

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          Most cited references55

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          Plants as source of drugs.

          This work presents a study of the importance of natural products, especially those derived from higher plants, in terms of drug development. It describes the main strategies for obtaining drugs from natural sources, fields of knowledge involved, difficulties and perspectives. It also includes a brief discussion of the specific situation in Brazil regarding the use of, trade in, and research into therapeutic resources of natural origin and the general lack of awareness of the use of potentially toxic plants, mainly in folk medicine.
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            Peptic ulcer disease.

            Peptic ulcer disease had a tremendous effect on morbidity and mortality until the last decades of the 20th century, when epidemiological trends started to point to an impressive fall in its incidence. Two important developments are associated with the decrease in rates of peptic ulcer disease: the discovery of effective and potent acid suppressants, and of Helicobacter pylori. With the discovery of H pylori infection, the causes, pathogenesis, and treatment of peptic ulcer disease have been rewritten. We focus on this revolution of understanding and management of peptic ulcer disease over the past 25 years. Despite substantial advances, this disease remains an important clinical problem, largely because of the increasingly widespread use of non-steroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. We discuss the role of these agents in the causes of ulcer disease and therapeutic and preventive strategies for drug-induced ulcers. The rare but increasingly problematic H pylori-negative NSAID-negative ulcer is also examined.
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              NSAID-induced gastric damage in rats: requirement for inhibition of both cyclooxygenase 1 and 2.

              Selective cyclooxygenase (COX)-2 inhibitors produce less gastric damage than conventional nonsteroidal anti-inflammatory drugs (NSAIDs), suggesting that NSAIDs cause damage by inhibiting COX-1. We tested this hypothesis in rats by using a selective COX-1 inhibitor (SC-560). The effects of SC-560, celecoxib (selective COX-2 inhibitor), or a combination of both inhibitors on gastric damage and prostaglandin synthesis were determined. Selectivity of the drugs for COX-1 vs. COX-2 was assessed in the carrageenan-airpouch model. A COX-1-preferential inhibitor, ketorolac, was also evaluated. The effects of these inhibitors on leukocyte adherence to vascular endothelium and on gastric blood flow were assessed. SC-560 markedly reduced gastric prostaglandin synthesis and platelet COX-1 activity, but spared COX-2 and did not cause gastric damage. Celecoxib did not affect gastric prostaglandin E(2) synthesis and did not cause gastric damage. However, the combination of SC-560 and celecoxib invariably caused hemorrhagic erosion formation, comparable to that seen with indomethacin. Ketorolac caused damage only at doses that inhibited both COX isoforms, or when given with a COX-2 inhibitor. Celecoxib, but not SC-560, significantly increased leukocyte adherence, whereas SC-560, but not celecoxib, reduced gastric blood flow. Inhibition of both COX-1 and COX-2 is required for NSAID-induced gastric injury in the rat.
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                Author and article information

                Journal
                Ulcers
                Ulcers
                Hindawi Limited
                2090-1526
                2090-1534
                2013
                2013
                : 2013
                : 1-12
                Affiliations
                [1 ]Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana
                [2 ]Department of Biochemistry, School of Biological Sciences, University of Cape Coast, Cape Coast, Ghana
                [3 ]Department of Molecular Biology and Biotechnology, School of Biological Sciences, University of Cape Coast, Cape Coast, Ghana
                [4 ]Department of Clinical Pathology, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana
                Article
                10.1155/2013/796405
                567b554b-fd18-4af4-a6df-27696b5fa4bc
                © 2013

                http://creativecommons.org/licenses/by/3.0/

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