Effect of Vitamin A Palmitate on Vitamin A-Deficient Rabbits

Kubo, Yoshikazu; Arimura, Akiko; Watanabe, Yasuo; Nakayasu, Kiyoo; Kanai, Atsushi

doi:10.1016/s0021-5155(99)00206-3

Cited by 3 publications

(8 citation statements)

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“… 7 In addition, the effectiveness of VApal in promoting wound healing (according to fluorescein staining evaluation) was confirmed by the results of our previous studies of experimental keratoconjunctival epithelial damage in rabbits 11 and dry eye models in rabbits 10 and rats, 12 as well as in dry eye-like symptoms induced by vitamin A deficiency in rabbits. 9 These results suggest that VApal improved wound healing in the corneal and conjunctival epithelium by promoting hyaluronic acid expression in the ocular tissue in addition to stabilizing the mucin layer as described earlier.…”

Section: Discussionsupporting

confidence: 71%

“…We investigated the pharmacology of VApal and reported improvements in mucin abnormalities (RB staining evaluation) after VApal administration in experimental keratoconjunctival epithelial damage induced by n -heptanol in rabbits11 and in dry eye models treated with alkali solution after the removal of lacrimal glands in rabbits10 and rats 12. We also confirmed that VApal promotes mucin gene12 and protein8,12 expression as well as the recovery of conjunctival goblet cell numbers 9,11. In addition, the dry eye therapeutic agents diquafosol sodium and rebamipide reportedly improve dry eye by decreasing mucin abnormality 21–24.…”

Section: Discussionmentioning

confidence: 58%

“…Furthermore, in studies using animal models for dry eye, we found that the administration of 500–1,500 IU/mL VApal improved corneal epithelial disorders9,10 and mucin covering disorders10,11 and aided in the recovery of conjunctival goblet cell numbers 9–11. Moreover, VApal was confirmed to promote mucin gene and protein expression during the healing of corneal conjunctival wounds 12…”

Section: Introductionmentioning

confidence: 85%

“… 12 We also confirmed that VApal promotes mucin gene 12 and protein 8 , 12 expression as well as the recovery of conjunctival goblet cell numbers. 9 , 11 In addition, the dry eye therapeutic agents diquafosol sodium and rebamipide reportedly improve dry eye by decreasing mucin abnormality. 21 – 24 These results suggest that in the present study of human subjects, VApal improved mucin abnormality in the keratoconjunctival epithelium by promoting mucin expression on the ocular surface and the recovery of conjunctival goblet cells.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

Toshida¹,

Funaki²,

Ono³

et al. 2017

DDDT

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PurposeThe purpose of this study was to investigate the efficacy and safety of the administration of retinol palmitate (VApal) ophthalmic solution (500 IU/mL) for the treatment of patients with dry eye.Patients and methodsThis study included 66 patients with dry eye. After a 2-week washout period, patients were randomized (1:1) into either a VApal ophthalmic solution or a placebo group, and a single drop of either solution was administered six times daily for 4 weeks. Efficacy measures were 12 subjective symptoms, rose bengal (RB) and fluorescein staining scores, tear film breakup time, and tear secretion. Safety measures included clinical blood and urine analyses and adverse event recordings.ResultsIn comparisons of the two groups, the mean change in RB staining score from baseline was significantly lower in the VApal group at 2 and 4 weeks (P<0.05 and P<0.01, respectively). Furthermore, the fluorescein clearance rate (fluorescein staining score) was significantly higher in the VApal group at 4 weeks (P<0.05). The VApal group showed a significant improvement in blurred vision at 1 and 2 weeks (P<0.01 and P<0.05, respectively), and the mean change in the total score for subjective symptoms from baseline was significantly lower in the VApal group at 1 week (P<0.05). In before- and after-intervention comparisons, the fluorescein and RB staining scores showed improvement in both groups. Improvement was noted for 11 subjective symptoms in the VApal group and for seven symptoms in the placebo group. No significant differences in adverse events and reactions were found between the groups.ConclusionVApal ophthalmic solution (500 IU/mL) is safe and effective for the treatment of patients with dry eye.

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Section: Discussionsupporting

confidence: 71%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

Toshida¹,

Funaki²,

Ono³

et al. 2017

DDDT

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“…With regard to the effect of VA on mucin production, we previously reported that retinol palmitate (VApal) promotes mucin production in cultured rabbit conjunctival tissue (in vitro)11 and that topical application of VA markedly improves keratoconjunctival epithelial damage and loss of conjunctival goblet cells 9. It was also reported that topical application of VApal promotes the healing of keratoconjunctival damage and recovery of conjunctival goblet cells and that its effect on keratoconjunctival epithelial damage is particularly strong in the mucin layer 12.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

Odaka¹,

Toshida²,

Ohta³

et al. 2012

OPTH

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PurposeWe examined the efficacy of retinol palmitate (VApal) for dry eyes using dry eye model rabbits whose lacrimal glands were resected.Materials and methodsAfter alkaline injury on keratoconjunctival epithelium, VApal eye drops were administered 6 times a day for 7 days. The efficacy of VApal was also compared with that of 0.1% hyaluronic acid eye drops.ResultsThe fluorescein staining and rose bengal scores showed a significant decrease compared with the score in the vehicle group at 7 days (P < 0.05) in the 1000 IU/mL VApal group and at both 3 days (P < 0.05) and 7 days (P < 0.01) in the 1500 IU/mL VApal group. Histological examination revealed recovery of the corneal epithelium, and PAS staining disclosed the recovery of mucin-producing lower palpebral conjunctival goblet cells after 7 days in the 1500 IU/mL VApal group compared with the vehicle group. Results from impression cytology showed a significant increase in density of conjunctival goblet cells compared with that in the vehicle group after 7 days in the 1000 IU/mL VApal group and after 3 and 7 days in the 1500 IU/mL VApal group. There were no significant changes in tear flow in either group. Topical application of VApal at 1500 IU/mL showed greater improvement than 0.1% hyaluronic acid in both fluorescein and rose bengal score and in the density of conjunctival goblet cells.ConclusionIt is suggested that VApal is effective for the improvement of keratoconjunctival epithelial damage associated with tear abnormalities, such as dry eyes.

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Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

Estrada‐Ortiz

Starokozhko

Steenwijk

et al. 2022

J of Applied Toxicology

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The biocide tetrakis(hydroxymethyl)phosphonium sulphate (THPS) and other members of the tetrakis(hydroxymethyl) phosphonium salts (THPX) family are associated with liver toxicity in several mammalian species and teratogenicity in rabbits. Malformations include skeletal changes and abnormalities in eye development and are very similar to those seen with vitamin A deficiency or excess. For this reason, it was hypothesized that teratogenicity of THPS(X) might be attributed to disturbances in retinol availability and/or metabolism as a result of maternal toxicity, for example, either due to insufficient dietary intake by the mothers or due to liver toxicity. Therefore, in the present study, liver toxicity and vitamin A homeostasis were studied in pregnant rabbits that were exposed to 13.8 or 46.0 mg/kg THPS during organogenesis and in precision‐cut liver slices of rats and rabbits exposed to 0–70 μM THPS. Results show that in vivo exposure to THPS leads to a marked reduction of food intake, increased plasma concentrations of γ‐glutamytransferase, degenerative changes in the liver and to changes in retinoid content in liver and plasma in the rabbits during organogenesis. In addition, THPS, both in vivo and ex vivo, caused a change in expression of proteins related to vitamin A metabolism and transport. Together, these observations could explain the birth defects observed in earlier teratogenicity studies.

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Effect of Vitamin A Palmitate on Vitamin A-Deficient Rabbits

Cited by 3 publications

References 0 publications

Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

Efficacy and safety of retinol palmitate ophthalmic solution in the treatment of dry eye: a Japanese Phase II clinical trial

Efficacy of retinol palmitate eye drops for dry eye in rabbits with lacrimal gland resection

Disruption of vitamin A homeostasis by the biocide tetrakis(hydroxymethyl) phosphonium sulphate in pregnant rabbits

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