Medicinal Plants Classification Biosynthesis and ... - Index of

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Aracely E. Chávez-Piña and Andrés Navarrete
RvE1 owns counter regulatory actions to inhibit PMN transendothelial migration in vitro
and also acts as a potent inhibitor of leukocyte infiltration [57]. Furthermore, administration
of EPA and aspirin in a model of mouse peritonitis model induced RvE1 generation in
exudates and reduced leukocyte infiltration. Also, in a model of colitis, RvE1 protected
against the damage by the decrement of leukocyte infiltration and proinflammatory gene
expression of TNF-α and other cytokines [58].
Resolvins has not been studied as a gastroprotective substance, however considering that
an increment on leukocyte adherence is involved in the pathogenesis for gastric injury for
several compounds and resolving anti-inflammatory properties. Resolvins could exert a
protective effect on compounds-induced gastric injury. This statement should be explored.
3.2.5. Hydrogen sulfide (H2S)
Hydrogen sulfide is synthesized endogenously from L-cysteine primarily via two
enzymes: cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS). In some tissues,
CSE and CBS are both required for H2S synthesis, whereas in others only one enzyme is
necessary [59]. CBS and CSE are expressed to different extents in neurons in brain and in the
enteric nervous system in the gut. H2S was studied first in vascular smooth muscle, where as
NO, H2S exhibits relaxing effect by direct action on ATP-sensitive K + channels [60]. CSE
and CBS are expressed in gastric mucosa and endogenous H2S apparently plays the role of a
protective factor against mucosal injury; H2S regulates gastric mucosal blood flow and
leukocyte adherence to the vascular endothelium [4]. Furthermore, aspirin and other NSAIDs
reduce H2S generation by directly modulating the expression activity of CSE and a releasing
of H2S (NaHS) protects against the reduction of mucosal blood flow cause by aspirin.
Glibenclamide, a KATP blocker reduced the anti-adhesive effects of H2S, whereas pinacidil, a
KATP opener, protects against mucosal injury caused by aspirin [4]. KATP channels mediate
gastric mucosa homeostasis [61].
Anti-inflammatory drugs have been synthesized to release H2S, for example a derivate of
diclofenac (ATB-337), which is linked to a H2S-releasing moiety, spares gastrointestinal
mucosa of injury. This compound did not stimulate leukocyte adherence to the vascular
endothelium of postcapillary mesenteric venules, in contrast to the effects of diclofenac [5],
this event is related with a lack on the increment in gastric granulocyte infiltration or
expression of leukocyte or endothelial adhesion molecules.
Furthermore, TNF-α contributes to gastric injury induced by NSAIDs and alcohol. ATB-
429, reduces the expression of many proinflammatory cytokines, while it did not change IL-
10 expression, an anti-inflammatory cytokine. ATB-429 consists of a molecule of
mesalamine linked via an ester bond to a molecule of ADT-OH [62]. ADT-OH has been
shown to liberate H2S when incubated in buffer and even greater generation was observed
when it was incubated on homogenate liver [63].
Besides, NaHS, a donor of H2S, possesses a dual effect on H2O2-caused cell death in
mucosal epithelial cells. This was performed in the experiments where NaHS induced a
strong protective action at 1.5 mM but slight aggravation of the toxicity at 0.5-1 mM. With
those results, it can be concluded that NaHS may directly protect gastric mucosal epithelial
cells against oxidative stress, and further studies give the tools for the elucidation that this via