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https://www.readbyqxmd.com/read/26349493/updates-on-aldose-reductase-inhibitors-for-management-of-diabetic-complications-and-non-diabetic-diseases
#1
REVIEW
Ajmer Singh Grewal, Shashikant Bhardwaj, Deepti Pandita, Viney Lather, Bhupinder Singh Sekhon
Diabetes mellitus occurrence has been associated to the modification of the physiological levels of glucose and is often accompanied by several long-term complications, namely neuropathy, nephropathy, retinopathy, cataract, and cardiovascular. Aldose reductase (AR) is an enzyme of aldoketo reductase super-family that catalyzes the conversion of glucose to sorbitol in the polyol pathway of glucose metabolism. In this context, aldose reductase inhibitors (ARIs) have received much attention worldwide. Decreased sorbitol flux through polyol pathway by ARIs could be an emerging target for the management of major complications of diabetes...
2016: Mini Reviews in Medicinal Chemistry
https://www.readbyqxmd.com/read/26272532/effects-of-aldose-reductase-inhibitor-on-microneurographically-assessed-peripheral-sympathetic-nerve-activity-in-rats
#2
Daisuke Sato, Masataka Kusunoki, Go Shinzawa, Zhonggang Feng, Atsuyoshi Nishina, Takao Nakamura
Autonomic neuropathy, one of the serious complications of diabetes, decreases quality of life. Aldose reductase inhibitor (ARI) blocks sorbitol production, and results in prevention of damage of nerve fibers. Beneficial effects of ARI have usually been confirmed through nerve conduction velocity tests in motor and sensory nerves. On the other hand, few reports have dealt with the effects of ARI on the small fiber activity such as sympathetic nerve one. In the present study, we administered eparlestat, ARI orally for 3weeks, to streptozotocin-induced diabetic (STZ+ARI) rats, and then recorded peripheral sympathetic nervous signal detected with microneurographic technique...
December 2015: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/25998127/hyperglycemia-promotes-schwann-cell-de-differentiation-and-de-myelination-via-sorbitol-accumulation-and-igf1-protein-down-regulation
#3
Wu Hao, Syoichi Tashiro, Tomoka Hasegawa, Yuiko Sato, Tami Kobayashi, Toshimi Tando, Eri Katsuyama, Atsuhiro Fujie, Ryuichi Watanabe, Mayu Morita, Kana Miyamoto, Hideo Morioka, Masaya Nakamura, Morio Matsumoto, Norio Amizuka, Yoshiaki Toyama, Takeshi Miyamoto
Diabetes mellitus (DM) is frequently accompanied by complications, such as peripheral nerve neuropathy. Schwann cells play a pivotal role in regulating peripheral nerve function and conduction velocity; however, changes in Schwann cell differentiation status in DM are not fully understood. Here, we report that Schwann cells de-differentiate into immature cells under hyperglycemic conditions as a result of sorbitol accumulation and decreased Igf1 expression in those cells. We found that de-differentiated Schwann cells could be re-differentiated in vitro into mature cells by treatment with an aldose reductase inhibitor, to reduce sorbitol levels, or with vitamin D3, to elevate Igf1 expression...
July 10, 2015: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/25519680/an-exploratory-randomised-double-blind-and-placebo-controlled-phase-2-study-of-a-combination-of-baclofen-naltrexone-and-sorbitol-pxt3003-in-patients-with-charcot-marie-tooth-disease-type-1a
#4
RANDOMIZED CONTROLLED TRIAL
Shahram Attarian, Jean-Michel Vallat, Laurent Magy, Benoît Funalot, Pierre-Marie Gonnaud, Arnaud Lacour, Yann Péréon, Odile Dubourg, Jean Pouget, Joëlle Micallef, Jérôme Franques, Marie-Noëlle Lefebvre, Karima Ghorab, Mahmoud Al-Moussawi, Vincent Tiffreau, Marguerite Preudhomme, Armelle Magot, Laurène Leclair-Visonneau, Tanya Stojkovic, Laura Bossi, Philippe Lehert, Walter Gilbert, Viviane Bertrand, Jonas Mandel, Aude Milet, Rodolphe Hajj, Lamia Boudiaf, Catherine Scart-Grès, Serguei Nabirotchkin, Mickael Guedj, Ilya Chumakov, Daniel Cohen
BACKGROUND: Charcot-Marie-Tooth type 1A disease (CMT1A) is a rare orphan inherited neuropathy caused by an autosomal dominant duplication of a gene encoding for the structural myelin protein PMP22, which induces abnormal Schwann cell differentiation and dysmyelination, eventually leading to axonal suffering then loss and muscle wasting. We favour the idea that diseases can be more efficiently treated when targeting multiple disease-relevant pathways. In CMT1A patients, we therefore tested the potential of PXT3003, a low-dose combination of three already approved compounds (baclofen, naltrexone and sorbitol)...
2014: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/25491744/polytherapy-with-a-combination-of-three-repurposed-drugs-pxt3003-down-regulates-pmp22-over-expression-and-improves-myelination-axonal-and-functional-parameters-in-models-of-cmt1a-neuropathy
#5
Ilya Chumakov, Aude Milet, Nathalie Cholet, Gwenaël Primas, Aurélie Boucard, Yannick Pereira, Esther Graudens, Jonas Mandel, Julien Laffaire, Julie Foucquier, Fabrice Glibert, Viviane Bertrand, Klaus-Armin Nave, Michael W Sereda, Emmanuel Vial, Mickaël Guedj, Rodolphe Hajj, Serguei Nabirotchkin, Daniel Cohen
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited sensory and motor peripheral neuropathy. It is caused by PMP22 overexpression which leads to defects of peripheral myelination, loss of long axons, and progressive impairment then disability. There is no treatment available despite observations that monotherapeutic interventions slow progression in rodent models. We thus hypothesized that a polytherapeutic approach using several drugs, previously approved for other diseases, could be beneficial by simultaneously targeting PMP22 and pathways important for myelination and axonal integrity...
2014: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/25454638/hereditary-motor-and-sensory-neuropathies-or-charcot-marie-tooth-diseases-an-update
#6
REVIEW
Meriem Tazir, Tarik Hamadouche, Sonia Nouioua, Stephane Mathis, Jean-Michel Vallat
Hereditary motor and sensory neuropathies (HMSN) or Charcot-Marie-Tooth (CMT) diseases are the most common degenerative disorders of the peripheral nervous system. However, the frequency of the different subtypes varies within distinct populations. Although more than seventy clinical and genetic forms are known to date, more than 80% of CMT patients in Western countries have genetic abnormalities associated with PMP22, MPZ, MFN2 and GJB1. Given the considerable genetic heterogeneity of CMT, we emphasize the interest of both clinical and pathological specific features such that focused genetic testing could be performed...
December 15, 2014: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/25205950/painful-diabetic-neuropathy-an-update
#7
REVIEW
Sharonjeet Kaur, Promila Pandhi, Pinaki Dutta
Diabetes, a silent killer, is a leading cause of neuropathy. Around 50% of diabetic patients develop peripheral neuropathy in 25 years. Painful diabetic neuropathy manifests as burning, excruciating, stabbing or intractable type of pain or presents with tingling or numbness. The pathophysiology of this condition is due to primarily metabolic and vascular factors. There is increase in sorbitol and fructose, glycated endproducts, reactive oxygen species and activation of protein kinase C in the diabetic state...
October 2011: Annals of Neurosciences
https://www.readbyqxmd.com/read/24618902/a-clinical-and-neuropathological-study-of-chinese-patients-with-diabetic-peripheral-neuropathy
#8
Guangren Li, Chenglin Sun, Yanjun Wang, Yujia Liu, Xiaokun Gang, Ying Gao, Fei Li, Xianchao Xiao, Guixia Wang
OBJECTIVE: To examine whether the neuropathological and metabolic changes of peripheral nerves are correlated to clinical features in diabetes mellitus type 2 patients with peripheral neuropathy. METHODS: 147 type 2 diabetic patients with signs/symptoms of diabetic peripheralneuropathy (DPN) aged 53.4 ± 12.3 years and 134 healthy volunteers aged 55.5 ± 11.7 years were investigated for fasting plasma glucose (FPG), hemoglobin A1C (HbA1c), and red blood cell sorbitol (RBC sorbitol) in addition to nerve conduction velocity (NCV)...
2014: PloS One
https://www.readbyqxmd.com/read/24607578/development-of-novel-pyrazolone-derivatives-as-inhibitors-of-aldose-reductase-an-eco-friendly-one-pot-synthesis-experimental-screening-and-in-silico-analysis
#9
Aparna Kadam, Bhaskar Dawane, Manisha Pawar, Harshala Shegokar, Kapil Patil, Rohan Meshram, Rajesh Gacche
Aldose reductase is the key enzyme of polypol pathway leading to accumulation of sorbitol. Sorbitol does not diffuse across the cell membranes easily and therefore accumulates within the cell, causing osmotic damage which leads to retinopathy (cataractogenesis), neuropathy and other diabetic complications. Currently, aldose reductase inhibitors like epalrestat, ranirestat and fidarestat are used for the amelioration of diabetic complications. However, such drugs are effective in patients having good glycemic control and less severe diabetic complications...
April 2014: Bioorganic Chemistry
https://www.readbyqxmd.com/read/23901876/discovery-of-new-selective-human-aldose-reductase-inhibitors-through-virtual-screening-multiple-binding-pocket-conformations
#10
Ling Wang, Qiong Gu, Xuehua Zheng, Jiming Ye, Zhihong Liu, Jiabo Li, Xiaopeng Hu, Arnold Hagler, Jun Xu
Aldose reductase reduces glucose to sorbitol. It plays a key role in many of the complications arising from diabetes. Thus, aldose reductase inhibitors (ARI) have been identified as promising therapeutic agents for treating such complications of diabetes, as neuropathy, nephropathy, retinopathy, and cataracts. In this paper, a virtual screening protocol applied to a library of compounds in house has been utilized to discover novel ARIs. IC50's were determined for 15 hits that inhibited ALR2 to greater than 50% at 50 μM, and ten of these have an IC50 of 10 μM or less, corresponding to a rather substantial hit rate of 14% at this level...
September 23, 2013: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/23671855/effects-of-long-term-treatment-with-ranirestat-a-potent-aldose-reductase-inhibitor-on-diabetic-cataract-and-neuropathy-in-spontaneously-diabetic-torii-rats
#11
Ayumi Ota, Akihiro Kakehashi, Fumihiko Toyoda, Nozomi Kinoshita, Machiko Shinmura, Hiroko Takano, Hiroto Obata, Takafumi Matsumoto, Junichi Tsuji, Yoh Dobashi, Wilfred Y Fujimoto, Masanobu Kawakami, Yasunori Kanazawa
We evaluated ranirestat, an aldose reductase inhibitor, in diabetic cataract and neuropathy (DN) in spontaneously diabetic Torii (SDT) rats compared with epalrestat, the positive control. Animals were divided into groups and treated once daily with oral ranirestat (0.1, 1.0, 10 mg/kg) or epalrestat (100 mg/kg) for 40 weeks, normal Sprague-Dawley rats, and untreated SDT rats. Lens opacification was scored from 0 (normal) to 3 (mature cataract). The combined scores (0-6) from both lenses represented the total for each animal...
2013: Journal of Diabetes Research
https://www.readbyqxmd.com/read/23492276/-systematic-and-management-of-diabetic-neuropathy
#12
Diem, Christ
Diabetic neuropathy (DN) is an important complication contributing to high morbidity and mortality of diabetic subjects. Primarily, interventional strategies aim at normalization hyperglycemia (to prevent development and progression of DN), at early diagnosis and at prevention of ulcers and amputations. In addition, an increasing number of pharmaceutical agents is used to symptomatically treat dysesthesia and pain associated with DN. During recent years attempts have been made to pharmacologically treat DN by acting on underlying patho-physiological mechanisms (e...
August 1, 2002: Therapeutische Umschau. Revue Thérapeutique
https://www.readbyqxmd.com/read/23195764/effect-of-byakangelicin-an-aldose-reductase-inhibitor-on-galactosemic-cataracts-the-polyol-contents-and-na-k-atpase-activity-in-sciatic-nerves-of-strepto-zotocin-induced-diabetic-rats
#13
K H Shin, S S Lim, D K Kim
Byakangelicin, a main furanocoumarin constituent isolated and characterized as an aldose reductase inhibitor from the roots of Angelica dahurica, was evaluated for usefulness in the treatment of galactosemic cataract and diabetic complications in animal experiments. Cataract formation and galactitol accumulation in the lenses of rats fed a 30% galactose diet were significantly prevented by intragastric (i.g.) administration of byakangelicin at a dose of 100 mg/kg for 14 days. Administration of the drug for 18 days was found to suppress sorbitol accumulation and cause a significant reversal of depleted myo-inositol contents as well as Na(+),K(+)ATPase activity in the sciatic nerves of streptozotocin-induced diabetic rats...
April 1998: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/23105858/reactive-oxygen-species-reactive-nitrogen-species-and-antioxidants-in-etiopathogenesis-of-diabetes-mellitus-type-2
#14
P P Singh, Farzana Mahadi, Ajanta Roy, Praveen Sharma
Diabetes mellitus type-2 (DMT-2) is a hyperglycemic syndrome with several characteristic features. It continues to rise unabatedly in all pockets of the world, parallels with affluence and can be controlled but not cured. It has a definite involvement of genetic component but environmental factors play overwhelmingly dominant role in etiopathogenesis. Insulin resistance (IR) and obesity are singular instigators of DMT-2. The various events cause critical defects in insulin signaling cascade followed by beta-cell dysfunction...
October 2009: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/22628202/in-vitro-and-in-vivo-aldose-reductase-inhibitory-activity-of-standardized-extracts-and-the-major-constituent-of-andrographis-paniculata
#15
Ciddi Veeresham, Ettireddy Swetha, Ajmeera Rama Rao, Kaleab Asres
Aldose reductase is the first enzyme in the polyol pathway and catalyzes the reduction of glucose to sorbitol by coupling with the oxidation of NADPH to NADP(+) . This sorbitol accumulation leads to various diabetic complications, including neuropathy, nephropathy, cataracts, and retinopathy. In the present study, aldose reductase inhibitory (ARI) activity of the methanolic as well as standardized extracts of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae) and its chief constituent, andrographolide, were studied using in vitro and in vivo methods...
March 2013: Phytotherapy Research: PTR
https://www.readbyqxmd.com/read/22285226/interplay-of-sorbitol-pathway-of-glucose-metabolism-12-15-lipoxygenase-and-mitogen-activated-protein-kinases-in-the-pathogenesis-of-diabetic-peripheral-neuropathy
#16
Roman Stavniichuk, Hanna Shevalye, Hiroko Hirooka, Jerry L Nadler, Irina G Obrosova
The interactions among multiple pathogenetic mechanisms of diabetic peripheral neuropathy largely remain unexplored. Increased activity of aldose reductase, the first enzyme of the sorbitol pathway, leads to accumulation of cytosolic Ca²⁺, essentially required for 12/15-lipoxygenase activation. The latter, in turn, causes oxidative-nitrosative stress, an important trigger of mitogen activated protein kinase (MAPK) phosphorylation. This study therefore evaluated the interplay of aldose reductase, 12/15-lipoxygenase, and MAPKs in diabetic peripheral neuropathy...
April 1, 2012: Biochemical Pharmacology
https://www.readbyqxmd.com/read/22082324/metabolic-correction-in-the-management-of-diabetic-peripheral-neuropathy-improving-clinical-results-beyond-symptom-control
#17
REVIEW
J R Miranda-Massari, M J Gonzalez, F J Jimenez, M Z Allende-Vigo, J Duconge
Current Clinical Management Guidelines of Diabetic Peripheral Neuropathy (DPN) are based on adequate glucose control and symptomatic pain relief. However, meticulous glycemic control could delay the onset or slow the progression of diabetic neuropathy in patients with DM type 2, but it does not completely prevent the progression of the disease. Complications of DPN as it continues its natural course, produce increasing pain and discomfort, loss of sensation, ulcers, infections, amputations and even death. In addition to the increased suffering, disability and loss of productivity, there is a very significant economic impact related to the treatment of DPN and its complications...
November 2011: Current Clinical Pharmacology
https://www.readbyqxmd.com/read/21833829/novel-insights-into-the-structural-requirements-for-the-design-of-selective-and-specific-aldose-reductase-inhibitors
#18
Hirdesh Kumar, Anup Shah, M Elizabeth Sobhia
Aldose reductase (ALR2) plays a vital role in the etiology of long-term diabetic microvascular complications (DMCs) such as retinopathy, nephropathy and neuropathy. It initializes the polyol pathway and under hyperglycemic conditions, catalyzes the conversion of glucose into sorbitol in the presence of NADPH. Many ALR2 inhibitors have been withdrawn from clinical trial studies due to their cross reactivity with other analogues enzymes or due to impairment with detoxification role of ALR2. To address these issues we characterized the possible rationalities behind the selectivity problem associated with the enzyme-inhibitor interactions...
May 2012: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/21725814/evaluation-of-mechanical-and-rheological-properties-of-metronidazole-gel-as-local-delivery-system
#19
Mitra Jelvehgari, Hassan Montazam
Rosacea is a chronic multifactorial vascular skin disorder that affects about 10 percent of the general population. Metronidazole is an effective antibiotic in the treatment of moderate-to severe rosacea. Metronidazole is a suitable drug in cases of resistance to tetracycline or erythromycin, but it has also been shown that oral metronidazole may increase the side effects (e.g., peripheral neuropathy). Oral metronidazole should not be used for more than three months, and hence topical metronidazole gel is the best therapeutic choice in rosacea (especially during pregnancy)...
June 2011: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/21527327/effective-compounds-group-of-mongolian-prescriptions-baimai-san-protect-against-peripheral-neuropathy-in-lower-limbs-of-rats-through-neuro-protective-effect
#20
Qing-Shan Liu, Zong-Ran Pang, Rui Liu, Guo-Rong He, Jian Cui, Xiao-ying Yin
ETHNOPHARMACOLOGICAL RELEVANCE: BAIMAI-SAN prescription is a famous Chinese minority complex prescription used for curing neuropathy. MATERIALS AND METHODS: The Effective Compounds Groups of BAIMAI-SAN (ECGBM) is determined by high through-put screening, and it includes picroside II, verbascose, taurine and ellagic acid and borneol. To research the potential protective effect of ECGBM on the function of peripheral neuropathy, diabetic rats with peripheral neuropathy were induced by streptozotocin and treated with ECGBM (0...
June 1, 2011: Journal of Ethnopharmacology
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