Ticlopidine prevents the formation but delays the healing of ethanol-induced gastric lesions in the rat

Sibilia, V.; Pagani, F.; Lattuada, N.; Luca, Veronica De; Guidobono, F.; Soglian, A.; Netti, C.

doi:10.1016/j.phrs.2007.01.017

Cited by 11 publications

(11 citation statements)

References 42 publications

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“…), a selective COX-1 inhibitor. At the doses used in these experiments, none of the COX inhibitors had any gastric lesions per se (data not shown), in agreement with previous studies (Brzozowski et al, 2006a;Sibilia et al, 2007). One hour after EtOH administration, the rats were killed and the ulcer index was assessed as described above.…”

Section: Drugssupporting

confidence: 89%

Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross‐talk

Sibilia

Pagani

Rindi

et al. 2008

British J Pharmacology

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Background and purpose: Ghrelin, a gut-brain peptide, is considered a gastroprotective factor in gastric mucosa. We investigated the role of prostaglandins (PG) and the possible interplay between PGs and nitric oxide (NO) in ghrelin gastroprotection against ethanol (EtOH)-induced gastric lesions. Experimental approach: We examined the effects of (1) central ghrelin (4 mg per rat) injection on PGE 2 accumulation in normal or EtOH-lesioned gastric mucosa, (2) pretreatment with indomethacin (10 mg kg À1 , p.o.), a non-selective cyclooxygenase (COX) inhibitor, and with a selective COX-1, SC560 (5 mg kg À1 , p.o.) or COX-2 inhibitor, celecoxib (3.5 mg kg À1 , p.o.) on ghrelin gastroprotection against 50% EtOH (1 mL per rat)-induced gastric lesions, (3) the NO synthase inhibitor, L-NAME (70 mg kg À1 , s.c), on gastric PGE 2 content in ghrelin-treated rats and (4) central ghrelin on the expression of constitutive and inducible NOS and COX mRNA and on the localization of the immunoreactivity for COX-2 in the gastric mucosa exposed to EtOH. Key results: Ghrelin increased PGE 2 in normal mucosa, whereas, it reversed the EtOH-induced PGE 2 surge. Ghrelin had no effect on mucosal COX-1 expression but reduced the EtOH-induced increase in COX-2 expression and immunoreactivity. Indomethacin and SC560, but not celecoxib, removed ghrelin gastroprotection. L-NAME prevented the PGE 2 surge induced by ghrelin and, like indomethacin, reduced EtOH-induced PGE 2 increase. Ghrelin enhanced eNOS expression and reduced iNOS mRNA. Conclusions and implications:This study shows that COX-1-derived PGs are mainly involved in ghrelin gastroprotection and that the constitutive-derived NO together with PGE 2 are involved in ghrelin gastroprotective activity.

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Section: Drugssupporting

confidence: 89%

Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross‐talk

Sibilia

Pagani

Rindi

et al. 2008

British J Pharmacology

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“…Control rats were treated intracerebroventricularly with an equal volume of saline and orally with the corresponding vehicle. At the dose used, INDO per se failed to induce any gastric lesions (data not shown), which is in agreement with previous studies [26,28]. …”

Section: Methodssupporting

confidence: 93%

TLQP-21, a VGF-Derived Peptide, Prevents Ethanol-Induced Gastric Lesions: Insights into Its Mode of Action

et al. 2010

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Background and Aim: TLQP-21, a peptide derived from the vgf gene, has been reported to play a role in the regulation of rat gastric motility, but its influence on gastric mucosal integrity is unknown. Experimental Approach: We investigated the effects of central (0.8–8 nmol/rat) or peripheral (48–240 nmol/kg) TLQP-21 administration on ethanol- (EtOH, 50%, 1 ml/rat) induced gastric lesions in the rat. The mechanisms involved in such activity were also examined. Results: Central TLQP-21 injection dose-dependently reduced EtOH-induced gastric lesions (ED₅₀ = 3.16 nmol), while peripheral TLQP-21 administration had no effect. The TLQP-21 gastroprotective effect against EtOH injury was accompanied by a significant increase in gastric prostaglandin E₂ (PGE₂) production linked to an increase in constitutive cyclooxygenase (COX) expression. The nitric oxide (NO) synthase inhibitor L-NAME (70 mg/kg, s.c.), the nonselective COX inhibitor indomethacin (10 mg/kg, orally) and capsaicin denervation removed TLQP-21 gastroprotection. Conclusions: This study shows for the first time that central TLQP-21 exerts a protective action on the gastric mucosa exposed to the noxious agent EtOH. TLQP-21 gastroprotection is mediated by constitutive-derived NO and PGE₂, and requires the integrity of sensory nerve fibers.

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“…Two principal mechanisms-decreased mucosal blood flow (MBF) and delayed mucosal cell proliferation-have been proposed to explain the basis for ethanol-induced AGML. Both ethanol-induced decrease of nitric oxide (NO) production and release, and a decrease of calcitonin gene-related peptide (CGRP) secretion from afferent nerves in the gastric mucosa lead to disturbances in MBF (Sibilia et al 2007;Brzozowski et al 2003Brzozowski et al , 2008Szolcsányi and Barthó 2001). Ethanol-induced increased oxidative stress and decreased levels of PGs (COX-2 derived) delay mucosal cell proliferation (Hernández-Muñoz et al 2000;Areche et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

et al. 2009

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In rats, ventromedial hypothalamic (VMH) lesions induce cell proliferation in the visceral organs (stomach, small intestine, liver, and pancreas) due to hyperactivity of the vagus nerve. To investigate the effects of selective gastric vagotomy on VMH lesion-induced cell proliferation and secretion of gastric acid, we assessed the mitotic index (the number of proliferating cell nuclear antigen (PCNA)-immunopositive cells per 1,000 cells in the gastric mucosal cell layer) and measured the volume of secreted basal gastric acid. Furthermore, to explore whether or not ethanol-induced acute gastric mucosal lesions (AGML) lead to ulcer formation in VMH-lesioned rats, we assessed the ulcer index of both sham-operated and VMH-lesioned rats after administration of ethanol. VMH lesions resulted in an increased mitotic index and thickness of the gastric mucosal cell layer and gave rise to the hypersecretion of gastric acid. Selective gastric vagotomy restored these parameters to normal without affecting cell proliferation in other visceral organs. Ethanol-induced AGML caused ulcers in sham VMH-lesioned rats, whereas VMH-lesioned rats were less likely to exhibit such ulcers. These results suggest that VMH lesion-induced vagally mediated cell proliferation in the visceral organs is associated with hyperfunction in these organs, and VMH lesion-induced resistance to ethanol may be due to thickening of the gastric mucosal cell layer resulting from cell proliferation in the gastric mucosa-this in turn is due to hyperactivity of the vagus nerve.

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Ticlopidine prevents the formation but delays the healing of ethanol-induced gastric lesions in the rat

Cited by 11 publications

References 42 publications

Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross‐talk

Central ghrelin gastroprotection involves nitric oxide/prostaglandin cross‐talk

TLQP-21, a VGF-Derived Peptide, Prevents Ethanol-Induced Gastric Lesions: Insights into Its Mode of Action

Effects of Gastric Vagotomy on Visceral Cell Proliferation Induced by Ventromedial Hypothalamic Lesions: Role of Vagal Hyperactivity

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