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Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

Asano T, Aida S, Suemasu S, Tahara K, Tanaka K, Mizushima T - Sci Rep (2015)

Bottom Line: Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying.Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity.We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT
Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

No MeSH data available.


Related in: MedlinePlus

Effect of gastroprotective drugs on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose of aldioxa, geranylgeranylacetone (GGA) or sucralfate. One hour later, 20 mg kg−1 of indomethacin was orally administered and 8 h later, stomachs were removed and gastric mucosal lesions were measured (a). The effect of GGA or sucralfate at indicated dose on clonidine-induced delayed gastric emptying was examined using the phenol red method as described in the legend of Fig. 1 (b). Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
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f2: Effect of gastroprotective drugs on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose of aldioxa, geranylgeranylacetone (GGA) or sucralfate. One hour later, 20 mg kg−1 of indomethacin was orally administered and 8 h later, stomachs were removed and gastric mucosal lesions were measured (a). The effect of GGA or sucralfate at indicated dose on clonidine-induced delayed gastric emptying was examined using the phenol red method as described in the legend of Fig. 1 (b). Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.

Mentions: Aldioxa is the generic name for the metal complex, dihydroxyaluminum allantoinate, which is hydrolyzed to allantoin and aluminium hydrate at the gastric mucosa2425. The molecular mechanism governing the gastroprotective effect of aldioxa is unclear; however, it was suggested that both the direct coating of the gastric mucosa with aluminium hydrate and the anti-inflammatory effect of allantoin are involved2627. To understand the relationship between aldioxa’s gastroprotective effect and its stimulatory effect on gastric emptying, we compared its dose-response profiles on these effects. As shown in Fig. 2a, compared to its actions on delayed gastric emptying (Fig. 1a), a much higher dose of aldioxa (1,600 mg kg−1) was required to suppress indomethacin-induced gastric lesions. We also examined the effects of other gastroprotective drugs on clonidine-induced delayed gastric emptying. Neither geranylgeranylacetone (GGA) nor sucralfate affected clonidine-induced delayed gastric emptying (Fig. 2b) at doses that could suppress indomethacin-induced gastric lesions (Fig. 2a).


Aldioxa improves delayed gastric emptying and impaired gastric compliance, pathophysiologic mechanisms of functional dyspepsia.

Asano T, Aida S, Suemasu S, Tahara K, Tanaka K, Mizushima T - Sci Rep (2015)

Effect of gastroprotective drugs on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose of aldioxa, geranylgeranylacetone (GGA) or sucralfate. One hour later, 20 mg kg−1 of indomethacin was orally administered and 8 h later, stomachs were removed and gastric mucosal lesions were measured (a). The effect of GGA or sucralfate at indicated dose on clonidine-induced delayed gastric emptying was examined using the phenol red method as described in the legend of Fig. 1 (b). Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664916&req=5

f2: Effect of gastroprotective drugs on clonidine-induced delayed gastric emptying.Mice fasted for 18 h were orally administered indicated dose of aldioxa, geranylgeranylacetone (GGA) or sucralfate. One hour later, 20 mg kg−1 of indomethacin was orally administered and 8 h later, stomachs were removed and gastric mucosal lesions were measured (a). The effect of GGA or sucralfate at indicated dose on clonidine-induced delayed gastric emptying was examined using the phenol red method as described in the legend of Fig. 1 (b). Values are mean ± s.e.m. *P < 0.05; **P < 0.01 (Tukey test). n.s., not significant. Experiments were replicated at least two times.
Mentions: Aldioxa is the generic name for the metal complex, dihydroxyaluminum allantoinate, which is hydrolyzed to allantoin and aluminium hydrate at the gastric mucosa2425. The molecular mechanism governing the gastroprotective effect of aldioxa is unclear; however, it was suggested that both the direct coating of the gastric mucosa with aluminium hydrate and the anti-inflammatory effect of allantoin are involved2627. To understand the relationship between aldioxa’s gastroprotective effect and its stimulatory effect on gastric emptying, we compared its dose-response profiles on these effects. As shown in Fig. 2a, compared to its actions on delayed gastric emptying (Fig. 1a), a much higher dose of aldioxa (1,600 mg kg−1) was required to suppress indomethacin-induced gastric lesions. We also examined the effects of other gastroprotective drugs on clonidine-induced delayed gastric emptying. Neither geranylgeranylacetone (GGA) nor sucralfate affected clonidine-induced delayed gastric emptying (Fig. 2b) at doses that could suppress indomethacin-induced gastric lesions (Fig. 2a).

Bottom Line: Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying.Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity.We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

View Article: PubMed Central - PubMed

Affiliation: Department of Drug Discovery and Development, Faculty of Pharmacy, Keio University, 1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan.

ABSTRACT
Delayed gastric emptying and impaired gastric accommodation (decreased gastric compliance) play important roles in functional dyspepsia (FD). Here we screen for a clinically used drug with an ability to improve delayed gastric emptying in rats. Oral administration of aldioxa (dihydroxyaluminum allantoinate) partially improved clonidine- or restraint stress-induced delayed gastric emptying. Administration of allantoin, but not aluminium hydroxide, restored the gastric emptying. Both aldioxa and allantoin inhibited clonidine binding to the α-2 adrenergic receptor, suggesting that antagonistic activity of the allantoin moiety of aldioxa on this receptor is involved in the restoration of gastric emptying activity. Aldioxa or aluminium hydroxide but not allantoin restored gastric compliance with restraint stress, suggesting that aluminium hydroxide moiety is involved in this restoration. We propose that aldioxa is a candidate drug for FD, because its safety in humans has already been confirmed and its ameliorating effect on both of delayed gastric emptying and impaired gastric compliance are confirmed here.

No MeSH data available.


Related in: MedlinePlus