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Gastroprotective Triterpenoids: Pharmacological Mechanism
adhesion molecules. Pretreatment with pentoxifylline, an inhibitor of TNF-α synthesis, dosedependently
reduced neutrophil accumulation in the gastric microcirculation and gastric
damage [93]. Moreover, acemetacin treatment also decreases TNF-α production and it is
related with its gastric safety [15]. The development of new compounds without the induction
on the expression on TNF- α could help to enhance the gastroprotective properties of some
drugs.
There are many factors that can play the role as gastroprotective substances. The most
studied of them are NO, PGs, and recently lipoxins and H2S. These substances regulate in
orchestra the gastric mucosal inflammation. When the absence of one of them is induced, the
over-expression of the other ones is produced to compose this decrement and maintain the
mucosal gastric defense.
4. Experimental Models to Study Gastroprotection
An experimental model for the study of gastroprotection requires the induction of
mucosa injury with the less as possible suffering of the animal. Between all the experimental
models the induction of injury for ethanol absolute and NSAIDs administration are the most
popular. However, administration of acidified ethanol (HCl:EtOH), NaOH, stress-induced
ulcer, pylorus ligation and acetic acid are used depending of the mechanism and expected
results from the researcher. In this chapter, we will describe the gastric damage induce by
ethanol and NSAIDs administration and the parameters that could be measured.
4.1. Ethanol Induce Gastric Damage
Oral administration of ethanol has been described to induce gastric damage; the severity
of the injury is related with the doses of ethanol. Absolute ethanol induces severe
histopathological changes in oxyntic mucosa of mouse and rat stomach consisting of acute
erosive hemorrhagic lesions, vascular congestion, edema and necrosis [94, 95]. Furthermore,
ethanol causes depletion of the gastric levels of proteins, nucleic acids, NP-SH (non-protein
sulfhydryl groups) and an increment on MDA (malondialdehyde) levels and decrement of
antioxidants substances [96].
Moreover, it has been described that depletion of NP-SH groups by ethanol increases the
content of free radicals mediate tissue injury by stimulating lipid peroxidation and membrane
damage [94].
Low doses of ethanol can induce damage as well; for example, administration of 25 % of
ethanol induced a decrement on mucus secretion and an increment on the acid juice secretion
[97]. However, this effect has been related lately with the termed cytoprotection adaptative.
Furthermore, administration of 50 % of ethanol induces injury by constriction of venules and
this effect is reverted by prostaglandin exogenous administration [98]. Absence of blood flow
develops extensive gastric mucosa damage within a short period of time after contact with
absolute ethanol. In contrast, no changes in blood flow exhibits no injury after ethanol
administration [99, 100].
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