Study of the Inhibitory Effects of Enteral Nutrition Formula on Indomethacin-Induced Gastric Lesions in Mice

Yoshimi, Takeshi; Yamagishi, Yoshiaki; Kanegawa, Issei; Suda, Megumi; Saiki, Rei; Tanaka, Kenichiro; Goda, Hitomi; Kudo, Toshiyuki; K, Ito

doi:10.3390/nu11123058

Cited by 3 publications

(5 citation statements)

References 27 publications

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“…On the other hand, such lesions were present in the groups that had received subcutaneous IND injections ( Figure 2 ), indicating that these injections had successfully produced a mouse model of gastric lesions. The results of these observations were similar to those seen when the same IND dose was administered orally [ 15 ]. Measurements of the number and area of gastric lesions showed that they were both lower in the EN_M + IND and EN_T + IND groups than in the water + IND group (percentage of numbers: EN_M + IND 89%, EN_T + IND 56%; area: EN_M + IND 61%, EN_T + IND 34% compared to the water + IND group) ( Figure 3 ).…”

Section: Discussionsupporting

confidence: 83%

“…We have previously shown that the oral administration of two types of enteral nutrition formula (EN_M and EN_T) was effective in suppressing gastric lesions induced by oral IND administration in mice [ 15 ]. It was suggested that the mechanism whereby orally administered enteral nutrition formulas prevented gastric lesions might involve some sort of interaction between the formula and IND while both were simultaneously present in the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

“…Measurements of the number and area of gastric lesions showed that they were both lower in the EN_M + IND and EN_T + IND groups than in the water + IND group (percentage of numbers: EN_M + IND 89%, EN_T + IND 56%; area: EN_M + IND 61%, EN_T + IND 34% compared to the water + IND group) ( Figure 3 ). Although the effects of these enteral nutrition formulas in inhibiting gastric lesions were weaker in comparison with their effects after the oral administration of IND (percentage of numbers: EN_M + IND 51%, EN_T + IND 60%; area: EN_M + IND 31%, EN_T + IND 24% compared to the water + IND group) [ 15 ], these results suggested that they were not the result of their direct interaction with IND in the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%

“…The enteral nutrition formulas used were Mermed ® One (400 kcal/400 mL) and Terumeal ® 2.0α (400 kcal/200 mL). Each was purchased from Terumo Corporation (Tokyo, Japan), and their ingredients are listed in the supplementary table of our previous report [ 15 ]. The IND was purchased from Nacalai Tesque (Kyoto, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…We have been investigating enteral nutrition formulas with the aim of resolving this issue, and we have previously shown that oral ingestion of two of these (Mermed ® One and Terumeal ® 2.0α, Terumo Corporation, Tokyo, Japan, which are classified as foods) act to suppress gastric lesions induced by the oral administration of indomethacin (IND) in mice. Neither of these two formulas affected the blood concentration of IND when it was administered orally [ 15 ]. These results suggested that these two enteral nutrition formulas may provide an alternative to drugs for the treatment of NSAID-induced ulcers, and, as such, they may be one means of resolving the problem of polypharmacy [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

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Gastroprotective Effect of Enteral Nutrition Formula in Mice Injected Subcutaneously with Indomethacin

et al. 2021

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We have previously shown that two enteral nutrition formulas suppressed gastric lesions induced by the oral administration of indomethacin (IND) in mice. However, the mechanism of their protective effect is unknown. In this study, the effect of the two enteral nutrition formulas on gastric lesions induced by subcutaneous IND injection was investigated, with the objective of exploring the possibility that they may interact directly with IND in the gastrointestinal tract. Ten-week-old, male, ICR mice were fasted, then orally given either purified water, Mermed® One, or 2-fold diluted Terumeal® 2.0α as enteral nutrition formula (25 mL/kg). IND was injected subcutaneously at 20 mg/kg after 30 min, and the stomach was removed 6 h later and fixed in formalin. The number and area of lesions in the stomachs of mice given enteral nutrition formula was reduced to 56–89% and 34–61%, respectively, compared with the mice given purified water. The time courses of plasma IND concentrations were comparable among the three groups. These results suggested that the effect of these enteral nutrition formulas on gastric lesions did not originate from their direct interaction with IND in the gastrointestinal tract or their effect on the disposition of IND.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Gastroprotective Effect of Enteral Nutrition Formula in Mice Injected Subcutaneously with Indomethacin

et al. 2021

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A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy

Hutka,

Várallyay,

László

et al. 2023

Acta Pharmacol Sin

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Lysophosphatidic acid (LPA) is a bioactive phospholipid mediator that has been found to ameliorate nonsteroidal anti-inflammatory drug (NSAID)-induced gastric injury by acting on lysophosphatidic acid type 2 receptor (LPAR2). In this study, we investigated whether LPAR2 signaling was implicated in the development of NSAID-induced small intestinal injury (enteropathy), another major complication of NSAID use. Wild-type (WT) and Lpar2 deficient (Lpar2−/−) mice were treated with a single, large dose (20 or 30 mg/kg, i.g.) of indomethacin (IND). The mice were euthanized at 6 or 24 h after IND treatment. We showed that IND-induced mucosal enteropathy and neutrophil recruitment occurred much earlier (at 6 h after IND treatment) in Lpar2−/− mice compared to WT mice, but the tissue levels of inflammatory mediators (IL-1β, TNF-α, inducible COX-2, CAMP) remained at much lower levels. Administration of a selective LPAR2 agonist DBIBB (1, 10 mg/kg, i.g., twice at 24 h and 30 min before IND treatment) dose-dependently reduced mucosal injury and neutrophil activation in enteropathy, but it also enhanced IND-induced elevation of several proinflammatory chemokines and cytokines. By assessing caspase-3 activation, we found significantly increased intestinal apoptosis in IND-treated Lpar2−/− mice, but it was attenuated after DBIBB administration, especially in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Finally, we showed that IND treatment reduced the plasma activity and expression of autotaxin (ATX), the main LPA-producing enzyme, and also reduced the intestinal expression of Lpar2 mRNA, which preceded the development of mucosal damage. We conclude that LPAR2 has a dual role in NSAID enteropathy, as it contributes to the maintenance of mucosal integrity after NSAID exposure, but also orchestrates the inflammatory responses associated with ulceration. Our study suggests that IND-induced inhibition of the ATX-LPAR2 axis is an early event in the pathogenesis of enteropathy.

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Prevention of gastrointestinal bleeding in critically ill patients

Al‐Dorzi

Arabi

2020

Current Opinion in Critical Care

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Purpose of review This review focuses on the current literature on the epidemiology and prevention of stress-induced clinically important gastrointestinal bleeding in ICU patients. Recent findings The incidence of stress-induced clinically important gastrointestinal bleeding in critically ill patients seems to be decreasing. Observational studies and an exploratory randomized controlled trial suggest that early enteral nutrition may be effective in preventing gastrointestinal bleeding in patients who are not at high risk. Recent systemic reviews and meta-analyses indicate that proton pump inhibitors and H2 receptor antagonists are more effective than placebo in preventing clinically important gastrointestinal bleeding, especially in high-risk and very high-risk patients, but do not reduce mortality. Although observational data suggested an association of proton pump inhibitors and H2 receptor antagonists with Clostridium difficile infection and pneumonia, this association was not confirmed in randomized controlled trials. Summary The incidence of stress-induced clinically important gastrointestinal bleeding in critically ill patients seems to have decreased over time. Even though stress ulcer prophylaxis in critically ill patients has been a research focus for decades, many questions remain unanswered, such as which groups of patients are likely to benefit and what pharmacologic agent is associated with the best benefit-to-harm ratio.

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Study of the Inhibitory Effects of Enteral Nutrition Formula on Indomethacin-Induced Gastric Lesions in Mice

Cited by 3 publications

References 27 publications

Gastroprotective Effect of Enteral Nutrition Formula in Mice Injected Subcutaneously with Indomethacin

Gastroprotective Effect of Enteral Nutrition Formula in Mice Injected Subcutaneously with Indomethacin

A dual role of lysophosphatidic acid type 2 receptor (LPAR2) in nonsteroidal anti-inflammatory drug-induced mouse enteropathy

Prevention of gastrointestinal bleeding in critically ill patients

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