A colon-specific prodrug of metoclopramide ameliorates colitis in an experimental rat model

Yang, Yunqing; Kim, Wooseong; Kim, Dayoon; Jeong, Seongkeun; Yoo, Jin‐Wook; Jung, Yunjin

doi:10.2147/dddt.s185257

Cited by 7 publications

(5 citation statements)

References 31 publications

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“…TH tyrosine hydroxylase duration of the dopaminergic response by reuptake of released DA [57]. Metoclopramide is a regulator of DA as well as serotonin receptors and commonly used for treating in addition to avoiding nausea and vomiting [58]. Metoclopramide at low dose could block dopamine receptors while at high doses it act as a 5-HT 3 receptor antagonist [10,59].…”

Section: Discussionmentioning

confidence: 99%

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Tian

Qian

et al. 2019

J Nat Med

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Gingerol, a biologically active component in ginger, has shown antiemetic properties. Our study aimed to explore the underlying mechanisms of gingerol on protecting rats and minks from chemotherapy-induced nausea and vomiting. The preventive impact of gingerol was evaluated in the pica model of rats and the vomiting model of minks induced by cisplatin at every 6 h continuously for a duration of 72 h. Animals were arbitrarily separated into blank control group, simple gingerol control group, cisplatin control group, cisplatin + metoclopramide group, cisplatin + three different doses gingerol group (low-dose; middle-dose; high-dose). The area postrema as well as ileum damage were assessed using H&E stain. The levels of 5-TH, 5-HT3 receptor, TPH, SERT, SP, NK1 receptor, PPT, NEP, DA, D2R, TH, and DAT were determined using immunohistochemistry or qRT-PCR in rats and minks. All indicators were measured in the area postrema along with ileum. The kaolin intake by rats and the incidence of CINV of minks were significantly decreased after pretreatment with gingerol in a dosage-dependent way for the duration of 0–24-h and 24–72-h. Gingerol markedly decreased the levels of 5-TH, 5-HT3 receptor, TPH, SP, NK1 receptor, PPT, DA, D2R, TH, alleviated area postrema as well as ileum damage, and increased the accumulation of SERT, NEP, DAT in the area postrema along with ileum of rats and minks. Gingerol alleviates cisplatin-induced kaolin intake of rats and emesis of minks possibly by regulating central and peripheral 5-HT system, SP system and DA system. Graphic abstract

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Section: Discussionmentioning

confidence: 99%

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Tian

Qian

et al. 2019

J Nat Med

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“…Metoclopramide is one of the benzamide prokinetic drugs acting as a 5-hydroxytryptamine 4 (5-HT 4 ) receptor agonist [ 20 - 22 ] and a 5-HT 3 and dopamine (D 2 ) receptor antagonist [ 6 ]. The distribution of 5-HT 4 receptors in the equine gut and the efficacy of different selective 5-HT 4 agonists have previously been investigated.…”

Section: Discussionmentioning

confidence: 99%

Ultrasonographic evaluation of the effects of the administration of neostigmine and metoclopramide on duodenal, cecal, and colonic contractility in Arabian horses: A comparative study

2020

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Background and Aim: As means for enhancing gastrointestinal (GI) motility, prokinetics have previously been evaluated in different breeds of horses with varying success. No previous studies were conducted to evaluate the effect of prokinetics on the intestinal tract of Arabian horses breed. Using B-mode ultrasound in the quantification of intestinal contractility, this study aimed to compare the impact of neostigmine and metoclopramide on the intestinal motility of healthy Arabian horses. Materials and Methods: Twenty-one clinically healthy Arabian horses were equally distributed into three groups. The control group was administered with 5 mL normal saline intramuscularly (IM). The second group was administered with neostigmine (0.044 mg/kg body weight [BW], IM), and the third group was administered with metoclopramide (0.25 mg/kg BW, IM). Duodenal, cecal, and colonic contractions were counted through ultrasonography for 3 min (pre-administration and 15, 30, 60, 120, and 180 min post-administration). Results: In the neostigmine group, a significant (p<0.05) increase in duodenal, cecal, and colonic contractions was observed 15 min post-administration compared with that in the control group (15±1.0, 11.33±1.53, and 12.33±2.31 vs. 11.0±2.0, 6.33±0.58, and 5.33±0.58 contractions per 3 min, respectively), continuing to 60 min post-administration for the duodenum and cecum and 120 min for colon and then returning to the normal; however, the metoclopramide group showed a significant (p<0.05) increase only in cecal and colonic contractions 60 min post-administration compared with the control group (11.0±1.0 and 12.33±0.58 vs. 6±1.0 and 5.67±0.58 contractions per 3 min, respectively), continuing until the end of the experiment. Excessive sweating, excitation, and straining were recorded following the administration of neostigmine, whereas no side effects were observed in the metoclopramide group. Conclusion: Neostigmine improves duodenal, cecal, and colonic contractions in healthy adult Arabian horses, whereas metoclopramide only improves cecal and colonic contractions. Metoclopramide appears to be safer and longer acting than neostigmine in the Arabian horse breed. Ultrasonography is a valuable noninvasive tool for the quantification of intestinal contractility. Future studies should consider the use of various dosages of metoclopramide and administration routes and investigate its impact on horses with GI transit disorders and inclusion in colic post-operative care.

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“…The cytokine concentrations of TNF-α and IL-1β in the culture supernatants from THP-1 cells stimulated with LPS alone, LPS + BMDA, or LPS + DMMA were analyzed with ELISA kits provided by R&D Systems (Minneapolis, MN, United States) in accordance with the manufacturer’s protocols. The level of cytokine-induced neutrophil chemoattractant (CINC)-3 in the agitated distal colon was also quantified with an ELISA kit (R&D Systems) as previously mentioned ( Yang et al, 2019 ).…”

Section: Elisamentioning

confidence: 99%

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis

et al. 2023

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As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1β production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA.

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A colon-specific prodrug of metoclopramide ameliorates colitis in an experimental rat model

Cited by 7 publications

References 31 publications

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Gingerol inhibits cisplatin-induced acute and delayed emesis in rats and minks by regulating the central and peripheral 5-HT, SP, and DA systems

Ultrasonographic evaluation of the effects of the administration of neostigmine and metoclopramide on duodenal, cecal, and colonic contractility in Arabian horses: A comparative study

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis

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