A wider view on gastric erosion: detailed evaluation of complex somatic and behavioral changes in rats treated with indomethacin at gastric ulcerogenic dose

Filaretova, Ludmila; Bagaeva, T. R.; Morozova, Olga; Zelena, Dóra

doi:10.4149/endo_2014_04_163

Cited by 4 publications

(2 citation statements)

References 46 publications

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“…2 The IND-induced gastric mucosal damage and dissociation of the luminal PCs as revealed by our study agree with previous studies. 9,15,37,51,54 . The significant time-dependent (from IND 6-12 hours) decrease in the number of the PCs (stained with anti-proton pump H + , K + -ATPase β-subunit) was consistent with the results of the gross and histopathological assessment, as well as with previous studies.…”

Section: Ind-induced Gastric Mucosal Erosions and Ulcerations Mainlmentioning

confidence: 99%

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis‐ and autophagy‐associated molecules

Gebril

Ito

Shibata

et al. 2020

Int J Experimental Path

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In clinical medicine, indomethacin (IND, a non-steroidal anti-inflammatory drug) is used variously in the treatment of severe osteoarthritis, rheumatoid arthritis, gouty arthritis or ankylosing spondylitis. A common complication found alongside the therapeutic characteristics is gastric mucosal damage. This complication is mediated through apoptosis and autophagy of the gastrointestinal mucosal epithelium. Apoptosis and autophagy are critical homeostatic pathways catalysed by caspases downstream of the gastrointestinal mucosal epithelial injury. Both act through molecular signalling pathways characterized by the initiation, mediation, execution and regulation of the cell regulatory cycle. In this study we hypothesized that dysregulated apoptosis and autophagy are associated with IND-induced gastric damage. We examined the spectra of in vivo experimental gastric ulcers in male Sprague-Dawley rats through gastric gavage of IND. Following an 18-hour fast, IND was administered to experimental rats. They were sacrificed at 3-, 6-and 12-hour intervals. Parietal cells (H + , K +-ATPase β-subunit assay) and apoptosis (TUNEL assay) were determined. The expression of apoptosis-signalling caspase (caspases 3, 8, 9 and 12), DNA damage (anti-phospho-histone H2A.X) and autophagy (MAP-LC3, LAMP-1 and cathepsin B)-related molecules in gastric mucosal cells was examined. The administration of IND was associated with gastric mucosal erosions and ulcerations mainly involving the gastric parietal cells (PCs) of the isthmic and upper neck regions and a time-dependent gradual increase in the number of apoptotic PCs with the induction of both apoptotic (upregulation of caspases 3 and 8) cell death and autophagic (MAP-LC3-II, LAMP-1 and cathepsin B) cell death. Autophagy induced by fasting and IND 3 hours initially prompted the degradation of caspase 8. After 6 and 12 hours, damping down of autophagic activity occurred, resulting in the upregulation of active caspase 8 and its nuclear translocation. In conclusion we report that IND can induce time-dependent apoptotic and autophagic cell death of PCs. Our | 231 GEBRIL Et aL. How to cite this article: Gebril SM, Ito Y, Shibata M-A, et al. Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis-and autophagy-associated molecules.

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Section: Ind-induced Gastric Mucosal Erosions and Ulcerations Mainlmentioning

confidence: 99%

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis‐ and autophagy‐associated molecules

Gebril

Ito

Shibata

et al. 2020

Int J Experimental Path

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“… 12 , 13 Recent research warns that certain NSAID medications affect the gut–brain axis, triggering broad systemic, endocrine, and behavioral changes, including disturbances in heart rate, body temperature, and anxiety-like behavior. 14 …”

Section: Introductionmentioning

confidence: 99%

Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract fromArthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation

Jensen

Drapeau

Lenninger

et al. 2016

Journal of Medicinal Food

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The goal for this study was to evaluate safety regarding anticoagulant activity and platelet activation during daily consumption of an aqueous cyanophyta extract (ACE), containing a high dose of phycocyanin. Using a randomized, double-blind, placebo-controlled study design, 24 men and women were enrolled after informed consent, and consumed either ACE (2.3 g/day) or placebo daily for 2 weeks. The ACE dose was equivalent to ∼1 g phycocyanin per day, chosen based on the highest dose Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. Consuming ACE did not alter markers for platelet activation (P-selectin expression) or serum P-selectin levels. No changes were seen for activated partial thromboplastin time, thrombin clotting time, or fibrinogen activity. Serum levels of aspartate transaminase (AST) showed a significant reduction after 2 weeks of ACE consumption (P < .001), in contrast to placebo where no changes were seen; the difference in AST levels between the two groups was significant at 2 weeks (P < .02). Reduced levels of alanine transaminase (ALT) were also seen in the group consuming ACE (P < .08). Previous studies showed reduction of chronic pain when consuming 1 g ACE per day. The higher dose of 2.3 g/day in this study was associated with significant reduction of chronic pain at rest and when physically active (P < .05). Consumption of ACE showed safety regarding markers pertaining to anticoagulant activity and platelet activation status, in conjunction with rapid and robust relief of chronic pain. Reduction in AST and ALT suggested improvement in liver function and metabolism.

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The Influence of Social Isolation and Enriched Environment on the Activity of the Hypothalamic–Pituitary–Adrenocortical (HPA) Axis, Pain Sensitivity, and Behavior in Rats after Exposure to an Ulcerogenic Stressor

Yarushkina,

Zenko,

Morozova

et al. 2024

J Evol Biochem Phys

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A wider view on gastric erosion: detailed evaluation of complex somatic and behavioral changes in rats treated with indomethacin at gastric ulcerogenic dose

Cited by 4 publications

References 46 publications

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis‐ and autophagy‐associated molecules

Indomethacin can induce cell death in rat gastric parietal cells through alteration of some apoptosis‐ and autophagy‐associated molecules

Clinical Safety of a High Dose of Phycocyanin-Enriched Aqueous Extract fromArthrospira (Spirulina) platensis: Results from a Randomized, Double-Blind, Placebo-Controlled Study with a Focus on Anticoagulant Activity and Platelet Activation

The Influence of Social Isolation and Enriched Environment on the Activity of the Hypothalamic–Pituitary–Adrenocortical (HPA) Axis, Pain Sensitivity, and Behavior in Rats after Exposure to an Ulcerogenic Stressor

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