Gastric mucosal changes induced by polyethylene glycol 400 administered by gavage in rats

Ueda, Yoshihide; Tsuboi, Masaru; Ota, Yasufumi; Makita, Maki; Aoshima, Takuya; Nakajima, Masahiro; Narama, Isao

doi:10.2131/jts.36.811

Cited by 13 publications

(13 citation statements)

References 15 publications

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“…Only transient vasoconstriction has been observed with recovery after 24 h of observation, which can be probably caused by edema of ectodermic layer. Similar observations of tissue edema were described in other studies [31][32][33]. On the other hand, PEG-400 acts as a skin and mucosa penetration enhancer for diffusion of other molecules and drugs and has been tested as a skin optical clearing agent [34,35].…”

supporting

confidence: 76%

Photodynamic Effect of Hypericin after Topical Application in the Ex Ovo Quail Chorioallantoic Membrane Model

et al. 2014

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Photosensitizing properties of hypericin are well known, and the chicken chorioallantoic membrane has previously been used to test photodynamic effects of hypericin and other substances. In our study the photodynamic effect of hypericin in the ex ovo quail chorioallantoic membrane model was evaluated. Steady-state and time-resolved fluorescence spectroscopy of hypericin solution in PEG-400 and its mixture in PBS was performed to assess and characterize the process of aggregation and disaggregation of hypericin during the drug formulation preparation. A therapeutical formulation (2 µg/g of embryo weight) was topically applied on CAM into the silicone ring. Hypericin was excited by diode laser with wavelength 405 nm, fluence rate 140 mW/cm2, and fluence 16.8 J/cm2. Hypericin in 100% PEG-400 exhibits typical fluorescence spectra with a maximum of about 600 nm, while hypericin 10% PEG-400 formulation exhibits almost no fluorescence. Time resolved spectra analysis showed fluorescence decay of hypericin in 100% PEG-400 solution with a mean lifetime of 5.1 ns and in 10% PEG 4.1 ns. Damage of quail chorioallantoic membrane vasculature after photodynamic therapy ranged from hemorrhage and vanishing of capillary vessels to thrombosis, lysis, and hemorrhage of larger vessels.The presented findings suggest that quail embryos can be used as a suitable model to test the effect of hypericin and other photodynamic compounds.

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confidence: 76%

Photodynamic Effect of Hypericin after Topical Application in the Ex Ovo Quail Chorioallantoic Membrane Model

et al. 2014

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“…50 For example, repeated oral administration of PEG400 (5, 50, or 100%) at a volume of 5 mL per kg per day for 15 days induces mucosal changes in the stomach, but not the intestine of rats. 51 In the study, no signicant changes in the general condition, body weight, food consumption, hematology, or gross ndings at necropsy were observed during the treatment period, with the exception of loose stools in rats treated with 50 or 100 v/v% PEG400. 51 We had veried that oral 50% PEG400 at 20 mL kg À1 did not cause acute toxicity in mice (data not shown).…”

Section: Discussionmentioning

confidence: 82%

“…51 In the study, no signicant changes in the general condition, body weight, food consumption, hematology, or gross ndings at necropsy were observed during the treatment period, with the exception of loose stools in rats treated with 50 or 100 v/v% PEG400. 51 We had veried that oral 50% PEG400 at 20 mL kg À1 did not cause acute toxicity in mice (data not shown). In this study, the results of LDH and protein assays suggested that PEG400 did not cause intestinal membrane damage.…”

Section: Discussionmentioning

confidence: 82%

Polyethylene glycol 400 (PEG400) affects the systemic exposure of oral drugs based on multiple mechanisms: taking berberine as an example

Yang

Dai

et al. 2017

RSC Adv.

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“…The only conspicuous clinical sign of toxicity was watery faeces in one individual rat that received the first low dose (17.5 mg/kg of C2) in the volume of 10 ml/kg, a common side effect of PEG-400 (Hermansky, et al 1995, Ueda, et al 2011). Subsequently, the volume administered was lowered to 5 ml/kg for the other rats, which ameliorated the diarrhoea.…”

Section: Acute Toxicitymentioning

confidence: 99%

Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats

Mahiout

Lindén

Esteban

et al. 2017

Toxicology and Applied Pharmacology

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The aryl hydrocarbon receptor (AHR) mediates the toxicity of dioxins, but also plays important physiological roles. Selective AHR modulators, which elicit some effects imparted by this receptor without causing the marked toxicity of dioxins, are presently under intense scrutiny. Two novel such compounds are IMA-08401 (N-acetyl-N-phenyl-4-acetoxy-5-chloro-1,2-dihydro-1-methyl-2-oxo-quinoline-3-carboxamide) and IMA-07101 (N-acetyl-N-(4-trifluoromethylphenyl)-4-acetoxy-1,2-dihydro-5-methoxy-1-methyl-2-oxo-quinoline-3-carboxamide). They represent, as diacetyl prodrugs, AHR-active metabolites of the drug compounds laquinimod and tasquinimod, respectively, which are intended for the treatment of autoimmune diseases and cancer. Here, we toxicologically assessed the novel compounds in Sprague-Dawley rats, after a single dose (8.75-92.5mg/kg) and 5-day repeated dosing at the highest doses achievable (IMA-08401: 100mg/kg/day; and IMA-07101: 75mg/kg/day). There were no overt clinical signs of toxicity, but body weight gain was marginally retarded, and the treatments induced minimal hepatic extramedullary haematopoiesis. Further, both the absolute and relative weights of the thymus were significantly decreased. Cyp1a1 gene expression was substantially increased in all tissues examined. The hepatic induction profile of other AHR battery genes was distinct from that caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The only marked alterations in serum clinical chemistry variables were a reduction in triglycerides and an increase in 3-hydroxybutyrate. Liver and kidney retinol and retinyl palmitate concentrations were affected largely in the same manner as reported for TCDD. In vitro, the novel compounds activated CYP1A1 effectively in H4IIE cells. Altogether, these novel compounds appear to act as potent activators of the AHR, but lack some major characteristic toxicities of dioxins. They therefore represent promising new selective AHR modulators.

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Gastric mucosal changes induced by polyethylene glycol 400 administered by gavage in rats

Cited by 13 publications

References 15 publications

Photodynamic Effect of Hypericin after Topical Application in the Ex Ovo Quail Chorioallantoic Membrane Model

Photodynamic Effect of Hypericin after Topical Application in the Ex Ovo Quail Chorioallantoic Membrane Model

Polyethylene glycol 400 (PEG400) affects the systemic exposure of oral drugs based on multiple mechanisms: taking berberine as an example

Toxicological characterisation of two novel selective aryl hydrocarbon receptor modulators in Sprague-Dawley rats

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