Effect of Long-Term Treatment of L-Ornithine on Visual Function and Retinal Histology in the Rats

Sakamoto, Kenji; Mori, Akira; Nakahara, Tsutomu; Murakami, Masahiko; Ishii, Kunio

doi:10.1248/bpb.b14-00491

Cited by 8 publications

(3 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[20][21][22][23]27,28) Briefly, animals were euthanized with an overdose of sodium pentobarbital. Both eyes were enucleated and fixed with a Davidson solution (37.5% ethanol, 9.3% paraformaldehyde, 12.5% acetic acid) for 24 h at room temperature.…”

Section: )mentioning

confidence: 99%

Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina

Shirai

Mori

Nakahara

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Endoplasmic reticulum stress has been reported to be involved in the pathogenesis of retinitis pigmentosa, macular degeneration and diabetic retinopathy. In the present study, we examined the effects of deferiprone, an iron chelator, on photoreceptor degeneration induced by tunicamycin (300 nmol/eye), an endoplasmic reticulum stress inducer, in the rat retina. Scotopic electroretinogram measurement and morphometric evaluation were done 7 d after the injection of tunicamycin. In the scotopic electroretinogram, intravitreal deferiprone (5 nmol/eye) injected simultaneously with tunicamycin significantly reduced the decreases in aand b-wave amplitudes induced by tunicamycin. Morphometric evaluation showed that deferiprone significantly reduced thinning of the outer nuclear layer, the inner segment and the outer segment. These results suggest that iron chelation therapy may be a good candidate for the treatment of eye diseases related to endoplasmic reticulum stress.Key words deferiprone; tunicamycin; endoplasmic reticulum stress; iron chelation Retinal degeneration involves various ocular disorders that characterized by the progressive death of retinal neurons. Although the mechanisms of photoreceptor cell death are not fully clarified, endoplasmic reticulum (ER) stress is one of candidates that cause macular degeneration, retinitis pigmentosa and diabetic retinopathy. 1) Tunicamycin is an antibiotic that inhibits the biosynthesis of N-acetylglucosaminylpyrophosphoryl polyisoprenol, a key intermediate in the formation of the asparagine-linked oligosaccharides of glycoproteins, 2) and widely known to induce ER stress.3) It has been reported that intravitreal tunicamycin causes photoreceptor-specific degeneration. 4,5) The intravitreal tunicamycin injection model is used for an animal model of photoreceptor-specific degeneration. [6][7][8][9] Increase of reactive oxygen species (ROS) is also known to cause ER stress, Parkinson's disease, 10-12) Alzheimer's disease, [11][12][13] and photoreceptor degeneration. 14) These ROS are believed to be generated at least in part by Fenton reaction, producing hydroxyl radical from hydrogen peroxide. It is well established that labile ferric iron, that does not form a complex with ferritin, is necessary for the Fenton reaction. Previous studies have demonstrated that chemical iron chelators, such as deferoxamine and VK-28, show neuroprotective effects in the animal models of Parkinson's disease 15) and Alzheimer's disease. 16)The aim of the present study was to determine whether iron chelation protects against photoreceptor degeneration induced by tunicamycin. Deferiprone (DFP), a chemical iron chelator that crosses the blood-brain barrier, 17) has shown efficacy with low toxicity in human.18) DFP has also been shown to decrease retinal labile iron without retinal toxicity in the mouse. 19) In the present study, we histologically and functionally examined whether intravitreal injection of DFP protects against tunicamycin-induced retinal degeneration. MATERIALS AND METHODSAnimals E...

show abstract

Section: )mentioning

confidence: 99%

Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina

Shirai

Mori

Nakahara

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…The plasma was separated by centrifugation, and then deproteinized with an equal volume of 3% (w/v) sulfosalicylic acid. The L-citrulline, L-arginine, and L-ornithine concentrations were measured with an amino acid analyzer (JLC-500/V; JEOL, Tokyo, Japan) as described elsewhere (Moinard et al, 2008;Morita et al, 2014;Sakamoto et al, 2015).…”

Section: Measurement Of the Plasma Concentrations Of L-citrulline L-arginine And L-ornithinementioning

confidence: 99%

L-Citrulline ameliorates the attenuation of acetylcholine-induced vasodilation of retinal arterioles in diabetic rats

Mori

Takei

Suzuki

et al. 2021

Heliyon

Self Cite

View full text Add to dashboard Cite

In our previous study, we found that the vasodilation of retinal arterioles induced by acetylcholine and BMS-191011, a large-conductance Ca 2+ -activated K + (BK Ca ) channel opener, were diminished in diabetic rats. Currently, few agents ameliorate the impaired vasodilator responses of retinal blood vessels. Our recent finding that the intravenous infusion of L-citrulline dilated retinal arterioles, suggests that L-citrulline could be a potential therapeutic agent for circulatory disorders of the retina. In this study, we determined the effect of an oral L-citrulline treatment on impaired acetylcholine- and BMS-191011-induced vasodilation in the retinal arterioles of diabetic rats. To induce diabetes, rats were administered an intravenous dose of streptozotocin (65 mg/kg) and a 5% D-glucose solution as drinking water. The L-citrulline (2 g/kg/day) and L-arginine (2 g/kg/day) treatments commenced either 15 days before or just after the streptozotocin injection and continued throughout the experimental period. A 29-day treatment with L-citrulline, but not L-arginine, significantly ameliorated the impaired acetylcholine- and BMS-191011-induced retinal vasodilation in diabetic rats without affecting their plasma glucose levels. The 2-week L-citrulline treatment tended to ameliorate the dysfunction of the acetylcholine-induced retinal vasodilation in diabetic rats. In conclusion, these results showed that the retinal blood vessel dysfunction induced by diabetes mellitus could be prevented by the long-term administration of L-citrulline and suggest that the latter could play a potentially prophylactic role in diabetic retinopathy.

show abstract

“…In this cycle, L-ornithine is a key precursor for the production of L-citrulline, L-proline and L-arginine, and the downstream product of L-ornithine is glutamate. L-ornithine has been attracted great attention for its biological functions [1] such as improving visual function [2] , regulating the secretion of hormones [3] , and is widely used in daily health and medical care such as the positive effect on the protection and vitality recovery of human liver and heart [4][5][6] . In addition, a recent report demonstrates that L-ornithine has a great prospect for the development of new anticancer drugs as raw material [7] .…”

Section: Introductionmentioning

confidence: 99%

Improvement of Xylose Utilization and L-ornithine Production by Metabolic Engineering of Corynebacterium glutamicum

Gao¹,

Zhang²,

Zhou³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: L-ornithine is a basic amino acid, which shows signi cant value in food and medicine industries. Xylose is the most important alternative carbon source of glucose in lignocellulosic hydrolysate. It is urgent to develop a high-e ciency cell factory for L-ornithine production with glucose and xylose. Results: In this study, the genes enconding xylose isomerase and xylulose kinase were introduced into Corynebacterium glutamicum S9114 to establish xylose metabolism pathway, and then xylose became a substitute carbon source of glucose. In addition, the optimization and overexpression of phosphoenolpyruvate carboxylase and pentose transporter had been conducted to promote the synthesis of L-ornithine for the rst time. Furthermore, though optimizing the concentration ratio of glucose and xylose (7:3), adding biotin and thiamine hydrochloride, we arrived at the highest L-ornithine yield 41.5g/L in shaking ask fermentation so far. Conclusions: Our results demonstrate that the combination of metabolic engineering and the optimization of fermentation process can make great potential for L-ornithine production by lignocellulose hydrolysate.

show abstract

Effect of Long-Term Treatment of L-Ornithine on Visual Function and Retinal Histology in the Rats

Cited by 8 publications

References 33 publications

Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina

Deferiprone Protects against Photoreceptor Degeneration Induced by Tunicamycin in the Rat Retina

L-Citrulline ameliorates the attenuation of acetylcholine-induced vasodilation of retinal arterioles in diabetic rats

Improvement of Xylose Utilization and L-ornithine Production by Metabolic Engineering of Corynebacterium glutamicum

Contact Info

Product

Resources

About