WordNet

limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
limit the range or extent of; "Contact between the young was inhibited by strict social customs"
a substance that retards or stops an activity
an enzyme that catalyses the biochemical reduction of some specified substance
a monosaccharide sugar that contains the aldehyde group or is hemiacetal

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〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
抑制する人(物) / 化学反応抑制剤

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/11/22 22:50:27」(JST)

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Aldose reductase inhibitors are a class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes.

Mechanism

Their target, aldose reductase, is an enzyme that is normally present in many other parts of the body, and catalyzes one of the steps in the sorbitol(polyol) pathway that is responsible for fructose formation from glucose. Aldose reductase activity increases as the glucose concentration rises in diabetes in those tissues that are not insulin sensitive, which include the lenses, peripheral nerves and glomerulus. Sorbitol does not diffuse through cell membranes easily and therefore accumulates, causing osmotic damage which leads to retinopathy and neuropathy.

Examples

Examples of aldose reductase inhibitors include:

tolrestat (withdrawn from market)
epalrestat
ranirestat^[1]
fidarestat

Diabetic cataract

Diabetic cataract formation follows an increase in sugars in the lens. The excess sugar within the lens is reduced by aldose reductase to its alcohol, but the lens capsule is relatively impermeable to sugar alcohols. Because of the excess sugar alcohol (polyol), the lens imbibes water, causing osmotic imbalance. Eventually, increased sodium and decreased potassium levels and decreased glutathione levels lead to cataract formation. Topical administration of aldose reductase inhibitors have been shown to prevent the cataract in rats.^[2]

Asthma and COPD

This class of drugs is also under investigation as a possible root pathology modulating treatment for asthma and COPD since it has been shown^[3] that they inhibit goblet cell metaplasia in the respiratory epithelium, thereby reducing the copious mucous secretion associated with these.

References

^ Várkonyi T, Kempler P (2007). "Diabetic neuropathy: new strategies for treatment". Diabetes, Obesity and Metabolism 10 (2): 070626012134005. doi:10.1111/j.1463-1326.2007.00741.x. PMID 17593238.
^ Newell, FW. Ophthalmology: Principles and Concepts, Fifth Edition. London: The CV Mosby Company, 1982, p. 332.
^ University of Texas Medical Branch at Galveston (2011, January 27). Discovery could lead to new therapies for asthma, COPD. ScienceDaily. Retrieved January 27, 2011, from http://www.sciencedaily.com /releases/2011/01/110127101325.htm?utm_source=feedburner&utm_medium=feed&utm_campaign=Feed%3A+sciencedaily+%28ScienceDaily%3A+Latest+Science+News%29&utm_content=Google+Reader

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1. 糖尿病合併症の予防におけるアルドース還元酵素阻害剤 aldose reductase inhibitors in the prevention of diabetic complications
2. 糖尿病性神経障害の治療 treatment of diabetic neuropathy
3. 糖尿病性網膜症：予防および治療 diabetic retinopathy prevention and treatment
4. 糖尿病における糸球体過剰ろ過の機序 mechanisms of glomerular hyperfiltration in diabetes mellitus
5. Chapter 4C：細胞容積の維持 chapter 4c maintenance of cell volume

English Journal

LC-MS/MS method for the quantification of aldose reductase inhibitor - Epalrestat and application to pharmacokinetic study.

Nirogi R, Kandikere V, Ajjala DR, Bhyrapuneni G, Muddana NR.SourceBiopharmaceutical Research, Suven Life Sciences Ltd., Serene Chambers, Road - 5, Avenue - 7, Banjara Hills, Hyderabad 500034, India. Electronic address: ramakrishna_nirogi@yahoo.co.in.
Journal of pharmaceutical and biomedical analysis.J Pharm Biomed Anal.2013 Feb 23;74:227-34. doi: 10.1016/j.jpba.2012.10.020. Epub 2012 Oct 23.
A simple and rapid LC-MS/MS method was developed and validated for the quantification of epalrestat, an aldose reductase inhibitor for the treatment of diabetic neuropathy. Following protein precipitation epalrestat and IS were eluted with 10mM ammonium acetate and acetonitrile using a rapid gradien
PMID 23245255

X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP(+) and the potent aldose reductase inhibitor fidarestat: Implications for inhibitor binding and selectivity.

Ruiz FX, Cousido-Siah A, Mitschler A, Farrés J, Parés X, Podjarny A.SourceInstitut de Génétique et de Biologie Moléculaire et Cellulaire, 1 rue Laurent Fries 67404 Illkirch CEDEX, France; Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, E-08193 Bellaterra, Barcelona, Spain.
Chemico-biological interactions.Chem Biol Interact.2013 Jan 4. pii: S0009-2797(12)00283-9. doi: 10.1016/j.cbi.2012.12.013. [Epub ahead of print]
Only one crystal structure is currently available for tumor marker AKR1B10, complexed with NADP(+) and tolrestat, which is an aldose reductase inhibitor (ARI) of the carboxylic acid type. Here, the X-ray structure of the complex of the V301L substituted AKR1B10 holoenzyme with fidarestat, an ARI of
PMID 23295227

Aldo-keto reductases mediate constitutive and inducible protection against aldehyde toxicity in human neuroblastoma SH-SY5Y cells.

Lyon RC, Li D, McGarvie G, Ellis EM.SourceStrathclyde Institute of Pharmacy & Biomedical Sciences, 161 Cathedral Street, University of Strathclyde, Glasgow G4 0RE, Scotland, UK; School of Science, University of the West of Scotland, Hamilton Campus, Almada Street, Hamilton ML3 0JB, Scotland, UK.
Neurochemistry international.Neurochem Int.2013 Jan;62(1):113-21. doi: 10.1016/j.neuint.2012.10.007. Epub 2012 Oct 22.
Reactive aldehydes including methyl glyoxal, acrolein and 4-hydroxy-2-nonenal (4-HNE) have been implicated in the progression of neurodegenerative diseases. The reduction of aldehydes to alcohols by the aldo-keto reductase (AKR) family of enzymes may represent an important detoxication route within
PMID 23084985