Nitric oxide in gastroprotection by aluminium-containing antacids

Konturek, Stanisław J.; Brzozowski, Tomasz; Majka, Jolanta; Szlachcic, Aleksandra; Nauert, C; Slomiany, Bronislaw L.

doi:10.1016/0014-2999(92)90550-n

Cited by 28 publications

(9 citation statements)

References 20 publications

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“…The capsaicin-induced protection seems to involve en dogenous PG because both the protective and circulatory effects of topical capsaicin were abolished by the pretreat ment with indomethacin in a dose capable of suppressing PG biosynthesis by about 90% [17][18][19]. Thus, our data support the concept of the involvement of endogenous PG in the protective and hyperemic action of capsaicin against lesions evoked by ethanol or stress.…”

Section: Discussionsupporting

confidence: 77%

“…This protective ac tion of intragastric capsaicin is accompanied by an in crease in gastric blood flow and both the gastric protective and circulatory effects seem to depend, at least in part, upon mucosal generation of PG because they were abol ished in rats pretreated with indomcthacin at a dose that is known to suppress this PG generation by about 90% [17][18][19]. Furthermore, this study provides evidence that capsaicin inhibits gastric acid and pepsin secretion.…”

Section: Discussionmentioning

confidence: 63%

“…), that was shown in our laboratory to inhibit PGEo activity by about 90% [17][18][19], the area of lesions provoked by 100% ethanol or WRS itself was slightly but significantly increased ( fig. 2).…”

Section: Effect O F Topical or Parenteral Acute Capsaicin Treatment Omentioning

confidence: 99%

“…pretreat Sensory Nerves in Gastroproteclion Digestion 1996;57:424-432 ment with indomethacin, given in the dose that was shown in the previous reports from our laboratory to suppress the generation of mucosal PGE; by about 90% [17,18]. These studies included the following groups of animals: ( I ) vehicle followed by 100% ethanol or WRS: (2) indomethacin injected i.p.…”

Section: Production O F Acute Gastric Lesionsmentioning

confidence: 99%

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Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Brzozowski

Sj²,

Śliwowski³

et al. 1996

Digestion

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Treatment with small doses of topical capsaicin protects the gastric mucosa from the damage by strong irritants but functional ablation of sensory nerves by pretreatment with larger dose of parenteral capsaicin augments the formation of gastric lesions via unknown mechanism. This study was designed to determine the role of gastric acid secretion, mucosal blood flow (GBF) and prostaglandins (PG) generation in the gastroprotection induced by small doses of topical or parenteral capsaicin in rats with intact or capsaicin-deactivated sensory nerves. Gastric lesions were produced in rats with intact sensory nerves (series A) or capsaicin-deactivated nerves (series B) using intragastric (i.g.) application of 100% ethanol, acidified aspirin (ASA) or water immersion and restraint stress (WRS). Pretreatment with i.g. capsaicin (0.12-1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-dependently the mucosal damage caused by ethanol, ASA or WRS, the dose inhibiting the lesion area by 50% (ID₅o) being 0.3, 0.5 and 0.7 mg/kg, respectively. This protection was accompanied by a significant rise in gastric mucosal blood flow (GBF). Parenteral application of capsaicin (1.2-10 mg/kg s.c.) that in intact rats dose-dependently increased GBF, also dose-dependently reduced gastric damage induced by ASA or WRS (but not by ethanol), the ID₅₀ being 5 and 3 mg/kg, respectively. The reduction by i.g. capsaicin of ethanol- or WRS-induced mucosal lesions was accompanied by a rise in GBF and this effect was reversed by indomethacin at a dose that suppressed endogenous PG biosynthesis by about 90%, indicating that PG are involved in the protective activities of topical capsaicin. Furthermore, topical and to a lesser extent parenteral capsaicin given to rats with intact or deactivated sensory nerves inhibited gastric acid and pepsin outputs, suggesting that this inhibition could contribute to the capsaicin-induced gastroprotection against acid-dependent mucosal lesions (ASA or WRS). Capsaicin deactiva-tion of sensory nerves aggravated mucosal lesions induced by all three ulcerogens and this effect was accompanied by a marked decrease in GBF. In such capsaicin-deactivated rats, topical capsaicin also reduced ethanol-, ASA- or WRS-induced lesions, while parenteral capsaicin was effective only in the protection against the damage induced by acidified ASA and WRS but not by ethanol. The protection against WRS lesions and accompanying rise in GBF by parenteral capsaicin were also reversed by the pretreatment with indomethacin applied in a dose suppressing the generation of PG. We conclude that capsaicin is capable of protecting gastric mucosa in rats with both intact and capsaicin-deactivated rats and that this protective activity depends, at least in part, upon its hyperemic and antisecretory effects that may be mediated, at least in part, by endogenous release of PG.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 63%

Section: Effect O F Topical or Parenteral Acute Capsaicin Treatment Omentioning

confidence: 99%

Section: Production O F Acute Gastric Lesionsmentioning

confidence: 99%

See 2 more Smart Citations

Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Brzozowski

Sj²,

Śliwowski³

et al. 1996

Digestion

Self Cite

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“…7). Similar effects have been observed after administration o f 'cytoprotective' drugs such as carbenoxolone [76], sucralfate [77] or aluminum-containing antacids [78] whose protective activity was reduced by the inhibition of NOS and reversed by the addition of L-argi- 8 …”

Section: Implication Of No In Gastric Cytoprotectionsupporting

confidence: 48%

Role of Nitric Oxide in the Digestive System

Konturek¹,

Konturek²

1995

Digestion

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Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa

Calatayud

Barrachina

Esplugues

2001

Microscopy Res & Technique

100

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Nitric oxide (NO) plays a multifaceted role in mucosal integrity. The numerous functions of NO and the double-edged role played by NO in most of them provide a great complexity to the NO action. The three enzymatic sources of NO, neuronal NO-synthase (nNOS), endothelial NOS (eNOS), and inducible NOS (iNOS), have been characterised in the gastrointestinal tract. The protective properties of the NO derived from constitutive NO-synthases (eNOS and nNOS) have already been well established. Less clear is the role assigned to iNOS. The simplistic initial view of low levels of NO synthesised by constitutive NOS being protective while exaggerated NO levels after iNOS induction leading irremediably to cytotoxicity is being questioned by new evidence. As initially reported for constitutive NOS, iNOS activity may be associated to reduced leukocyte-endothelium interaction and platelet aggregation as well as protection of mucosal microcirculation. Moreover, iNOS activity may be important to resolve inflammation by increasing apoptosis in inflammatory cells. It is entirely possible that a low level of expression of iNOS will reflect a positive host-defense response to challenge, but that exaggerated or uncontrolled expression of iNOS itself becomes detrimental. There is no doubt about the protective role of NO in physiological conditions. However, when the mucosa is threatened, the role of NO becomes multiple and the final effect will probably depend on the nature of the insult, the environment involved, and the interaction with other mediators.

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Nitric oxide in gastroprotection by aluminium-containing antacids

Cited by 28 publications

References 20 publications

Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Role of Capsaicin-Sensitive Sensory Nerves in Gastroprotection against Acid-Independent and Acid-Dependent Ulcerogens

Role of Nitric Oxide in the Digestive System

Nitric oxide: Relation to integrity, injury, and healing of the gastric mucosa

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