Medicinal Plants Classification Biosynthesis and ... - Index of

102
Aracely E. Chávez-Piña and Andrés Navarrete
induced gastropathy in rats, and this effect is reversed by concomitant administration of L-
NAME (an inhibitor of NO synthesis). This mechanism is mediated by the reduction of
leukocyte adhesion and maintenance of gastric blood flow [24].
Functional maintenance of gastric blood flow plays an important role in gastric mucosa
defense [25]. This maintenance of normal gastric blood flow occurs even in the presence of
damaging agents such as NSAIDs or ethanol [24, 25].
3.1.3. Motility
Normal gastric motility has been related with the mucosal gastric defense. NSAIDs
induce gastric injury throw PGs inhibition. Those drugs induce hipermotility which is an
important step for gastric damage induction. Furthermore, gastric hipermotility induced by
NSAIDs is associated with a PG deficiency caused by COX-1 inhibition; this was
demonstrated in some experiments where gastric hipermotility was induced after
indomethacin and SC-560 (COX-1 inhibitor) administration but not with rofecoxib (COX-2
inhibitor) treatment [26]. Moreover, sildenafil modifies gastroduodenal motility in both
humans [27] and animals [28].
The basis for the protection from gastric motility is a decrement on it. Glucorticoids are
assumed to protect gastric mucosa via their maintenance of glucose homeostasis, gastric
blood flow, and mucus secretion and their attenuation of enhanced gastric motility and
microvascular permeability [29]. It is thought that gastric hipermotility event decreases
gastric blood flow, explaining its pathogenicity.
3.2. Humoral Factors
3.2.1. Prostaglandins (PGs)
The first knowledge of prostaglandins occurred in 1930 with the observations of von
Euler and Goldblatt of some substances in semen that cause smooth muscle contractions;
their name come due to these substances where study by first time in prostate and was
proposed during Bergström, Samuelson and co-workers studies, who determined
prostaglandins structures. During 1971, Sir John Vane and colleagues discover the action of
aspirin and related anti-inflammatory drug as inhibitors of PGs.
Prostaglandins are eicosanoids derived from arachidonic acid by the initial action of
cyclooxygenase (PG endoperoxide G/H synthase). Arachidonic acid is a fatty acid derived
from dietary sources or is synthesized in the body from an essential fatty acid, linoleic acid. It
is stored in lipid bilayers of cell membranes and is esterified predominantly to phospholipids
such as phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol by an
enzyme named phospholipase A2 (PLA2) [30].
Prostaglandins are divided into series that differ in the oxygen substitution in the
cyclopentane ring and coded by a letter (PGD, PGE, PGF, PGG, and PGH). The subscript
numeral in PG nomenclature indicates the number of double bonds present in the compound
[30]. Cyclooxygenase (COX) is a heme-containing enzyme that is most abundant in the
endoplasmic reticulum. There are two major isoenzymes COX-1 and COX-2 and catalyzes
two reactions: cyclization of arachidonic acid to form PGG2 and hydroperoxidation of PGG2