Sorbinil, an Aldose Reductase Inhibitor, in Fighting Against Diabetic Complications

Author(s): Qi Huang, Qiong Liu, Dongsheng Ouyang*.

Journal Name: Medicinal Chemistry

Volume 15 , Issue 1 , 2019

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Abstract:

Background: Aldose reductase (AR) is involved in the pathogenesis of diabetes, which is one of the major threats to global public health.

Objective: In this review article, we have discussed the role of sorbinil, an AR inhibitor (ARI), in preventing diabetic complications.

Results: AR contributes in diabetes by generating excess intracellular superoxide and other mediators of oxidative stress through polyol pathway. Inhibition of AR activity thus might be a potential approach for the management of diabetic complications. Experimental evidences indicated that sorbinil can decrease AR activity and inhibit polyol pathway. Both in vitro and animal model studies reported the efficacy of sorbinil in controlling the progression of diabetes. Moreover, Sorbinil has been found to be comparatively safer than other ARIs for human use. But, it is still in earlyphase testing for the treatment of diabetic complications clinically.

Conclusion: Sorbinil is an effective ARI, which could play therapeutic role in treating diabetes and diabetic complications. However, advanced clinical trials are required for sorbinil so that it could be applied with the lowest efficacious dose in humans.

Keywords: Aldose reductase, diabetes, polyol pathway, sorbinil, β-cell dysfunction, blood glucose levels.

[1]
Andrés, R.C.; Helena, B.C.; Juliana, P.P.; Viviana, A.M.; Margarita, G.B.; Marisa, C.G. Diabetes-related neurological implications and pharmacogenomics. Curr. Pharm. Des., 2018, 24, 1695-1710.
[2]
Hugill, A.J.; Stewart, M.E.; Yon, M.A.; Probert, F.; Cox, I.J.; Hough, T.A.; Scudamore, C.L.; Bentley, L.; Wall, G.; Wells, S.E.; Cox, R.D. Loss of arylformamidase with reduced thymidine kinase expression leads to impaired glucose tolerance. Biol. Open, 2015, 4, 1367-1375.
[3]
Testa, R.; Bonfigli, A.R.; Genovese, S.; De Nigris, V.; Ceriello, A. The possible role of flavonoids in the prevention of diabetic complications. Nutrients, 2016, 8, E310.
[4]
Gu, J.; Yan, J.; Wu, W.; Huang, Q.; Ouyang, D. Research progress in aldose reductase. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2010, 35, 395-400.
[5]
Vedantham, S.; Ananthakrishnan, R.; Schmidt, A.M.; Ramasamy, R. Aldose reductase, oxidative stress and diabetic cardiovascular complications. Cardiovasc. Hematol. Agents Med. Chem., 2012, 10, 234-240.
[6]
Thiagarajan, D.; Ananthakrishnan, R.; Zhang, J.; O’Shea, K.M.; Quadri, N.; Li, Q.; Sas, K.; Jing, X.; Rosario, R.; Pennathur, S.; Schmidt, A.M.; Ramasamy, R. Aldose Reductase Acts as a Selective Derepressor of PPARγ and the Retinoic Acid Receptor. Cell Rep, 2016, 15, 181-196.
[7]
Forbes, J.M.; Cooper, M.E. Mechanisms of diabetic complications. Physiol. Rev., 2013, 93, 137-188.
[8]
El Gamal, H.; Eid, A.H.; Munusamy, S. Renoprotective Effects of Aldose Reductase Inhibitor Epalrestat against High Glucose-Induced Cellular Injury. Biomed Res. Int., 2017, 2017, 5903105.
[9]
Abdul Nasir, N.A.; Agarwal, R.; Sheikh Abdul Kadir, S.H.; Vasudevan, S.; Tripathy, M.; Iezhitsa, I.; Mohammad Daher, A.; Ibrahim, M.I.; Mohd Ismail, N. Reduction of oxidative-nitrosative stress underlies anticataract effect of topically applied tocotrienol in streptozotocin-induced diabetic rats. PLoS One, 2017, 12, e0174542.
[10]
Dodda, D.; Ciddi, V. Plants used in the management of diabetic complications. Indian J. Pharm. Sci., 2014, 76, 97-106.
[11]
Tammali, R.; Srivastava, S.K.; Ramana, K.V. Targeting aldose reductase for the treatment of cancer. Curr. Cancer Drug Targets, 2011, 11, 560-571.
[12]
Grewal, A.S.; Bhardwaj, S.; Pandita, D.; Lather, V.; Sekhon, B.S. Updates on Aldose Reductase Inhibitors for Management of Diabetic Complications and Non-diabetic Diseases. Mini Rev. Med. Chem., 2016, 16, 120-162.
[13]
Chang, K.C.; Snow, A.; LaBarbera, D.V.; Petrash, J.M. Aldose reductase inhibition alleviates hyperglycemic effects on human retinal pigment epithelial cells. Chem. Biol. Interact., 2015, 234, 254-260.
[14]
Brings, S.; Fleming, T.; Freichel, M.; Muckenthaler, M.U.; Herzig, S.; Nawroth, P.P. Dicarbonyls and advanced glycation end-products in the development of diabetic complications and targets for intervention. Int. J. Mol. Sci, 2017, 18, E984.
[15]
Yadav, U.C.; Srivastava, S.K.; Ramana, K.V. Understanding the role of aldose reductase in ocular inflammation. Curr. Mol. Med., 2010, 10, 540-549.
[16]
Wu, J.; Jin, Z.; Yan, L.J. Redox imbalance and mitochondrial abnormalities in the diabetic lung. Redox Biol., 2017, 11, 51-59.
[17]
ElGamal, H.; Munusamy, S. Aldose reductase as a drug target for treatment of diabetic nephropathy: Promises and challenges. Protein Pept. Lett., 2017, 24, 71-77.
[18]
Forbes, J.M.; Coughlan, M.T.; Cooper, M.E. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes, 2008, 57, 1446-1454.
[19]
Huang, Z.; Hong, Q.; Zhang, X.; Xiao, W.; Wang, L.; Cui, S.; Feng, Z.; Lv, Y.; Cai, G.; Chen, X.; Wu, D. Aldose reductase mediates endothelial cell dysfunction induced by high uric acid concentrations. Cell Commun. Signal., 2017, 15, 3.
[20]
Javed, S.; Alam, U.; Malik, R.A. Burning through the pain: treatments for diabetic neuropathy. Diabetes Obes. Metab., 2015, 17, 1115-1125.
[21]
Østergaard, L.; Finnerup, N.B.; Terkelsen, A.J.; Olesen, R.A.; Drasbek, K.R.; Knudsen, L.; Jespersen, S.N.; Frystyk, J.; Charles, M.; Thomsen, R.W.; Christiansen, J.S.; Beck-Nielsen, H.; Jensen, T.S.; Andersen, H. The effects of capillary dysfunction on oxygen and glucose extraction in diabetic neuropathy. Diabetologia, 2015, 58, 666-677.
[22]
Li, Q.R.; Wang, Z.; Zhou, W.; Fan, S.R.; Ma, R.; Xue, L.; Yang, L.; Li, Y.S.; Tan, H.L.; Shao, Q.H.; Yang, H.Y. Epalrestat protects against diabetic peripheral neuropathy by alleviating oxidative stress and inhibiting polyol pathway. Neural Regen. Res., 2016, 11, 345-351.
[23]
Robinson, R.; Barathi, V.A.; Chaurasia, S.S.; Wong, T.Y.; Kern, T.S. Update on animal models of diabetic retinopathy: from molecular approaches to mice and higher mammals. Dis. Model. Mech., 2012, 5, 444-456.
[24]
Pradhan, P.; Upadhyay, N.; Tiwari, A.; Singh, L.P. Genetic and epigenetic modifications in the pathogenesis of diabetic retinopathy: a molecular link to regulate gene expression. New Front Ophthalmol, 2016, 2, 192-204.
[25]
Safi, S.Z.; Qvist, R.; Kumar, S.; Batumalaie, K.; Ismail, I.S. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets. Biomed Res. Int., 2014, 2014, 801269.
[26]
Watarai, A.; Nakashima, E.; Hamada, Y.; Watanabe, G.; Naruse, K.; Miwa, K.; Kobayashi, Y.; Kamiya, H.; Nakae, M.; Hamajima, N.; Sekido, Y.; Niwa, T.; Oiso, Y.; Nakamura, J. Aldose reductase gene is associated with diabetic macroangiopathy in Japanese Type 2 diabetic patients. Diabet. Med., 2006, 23, 894-899.
[27]
Yang, B.; Millward, A.; Demaine, A. Functional differences between the susceptibility Z-2/C-106 and protective Z+2/T-106 promoter region polymorphisms of the aldose reductase gene may account for the association with diabetic microvascular complications. Biochim. Biophys. Acta, 2003, 1639, 1-7.
[28]
Hao, X.; Han, Z.; Zhu, C. Topical composition for treating diabetic cataracts: a patent evaluation (WO2015026380A1). Expert Opin. Ther. Pat., 2016, 26, 731-735.
[29]
Coppey, L.J.; Gellett, J.S.; Davidson, E.P.; Dunlap, J.A.; Yorek, M.A. Effect of antioxidant treatment of streptozotocin-induced diabetic rats on endoneurial blood flow, motor nerve conduction velocity, and vascular reactivity of epineurial arterioles of the sciatic nerve. Diabetes, 2001, 50, 1927-1937.
[30]
Obrosova, I.G.; Fathallah, L. Evaluation of an aldose reductase inhibitor on lens metabolism, ATPases and antioxidative defense in streptozotocin-diabetic rats: an intervention study. Diabetologia, 2000, 43, 1048-1055.
[31]
Ramana, K.V.; Tammali, R.; Reddy, A.B.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase-regulated tumor necrosis factor-alpha production is essential for high glucose-induced vascular smooth muscle cell growth. Endocrinology, 2007, 148, 4371-4384.
[32]
Asnaghi, V.; Gerhardinger, C.; Hoehn, T.; Adeboje, A.; Lorenzi, M. A role for the polyol pathway in the early neuroretinal apoptosis and glial changes induced by diabetes in the rat. Diabetes, 2003, 52, 506-511.
[33]
Sun, W.; Gerhardinger, C.; Dagher, Z.; Hoehn, T.; Lorenzi, M. Aspirin at low-intermediate concentrations protects retinal vessels in experimental diabetic retinopathy through non-platelet-mediated effects. Diabetes, 2005, 54, 3418-3426.
[34]
Dagher, Z.; Park, Y.S.; Asnaghi, V.; Hoehn, T.; Gerhardinger, C.; Lorenzi, M. Studies of rat and human retinas predict a role for the polyol pathway in human diabetic retinopathy. Diabetes, 2004, 53, 2404-2411.
[35]
Gerhardinger, C.; Dagher, Z.; Sebastiani, P.; Park, Y.S.; Lorenzi, M. The transforming growth factor-beta pathway is a common target of drugs that prevent experimental diabetic retinopathy. Diabetes, 2009, 58, 1659-1667.
[36]
Nencetti, S.; La Motta, C.; Rossello, A.; Sartini, S.; Nuti, E.; Ciccone, L.; Orlandini, E.N. -(Aroyl)-N-(arylmethyloxy)-α-alanines: Selective inhibitors of aldose reductase. Bioorg. Med. Chem., 2017, 25, 3068-3076.
[37]
Chang, K.C.; Ponder, J.; Labarbera, D.V.; Petrash, J.M. Aldose reductase inhibition prevents endotoxin-induced inflammatory responses in retinal microglia. Invest. Ophthalmol. Vis. Sci., 2014, 55, 2853-2861.
[38]
Ramana, K.V.; Friedrich, B.; Tammali, R.; West, M.B.; Bhatnagar, A.; Srivastava, S.K. Requirement of aldose reductase for the hyperglycemic activation of protein kinase C and formation of diacylglycerol in vascular smooth muscle cells. Diabetes, 2005, 54, 818-829.
[39]
Bhatnagar, A.; Ruef, J.; Liu, S.; Srivastava, S.; Srivastava, S.K. Regulation of vascular smooth muscle cell growth by aldose reductase. Chem. Biol. Interact., 2001, 130-132, 627-636.
[40]
Tammali, R.; Saxena, A.; Srivastava, S.K.; Ramana, K.V. Aldose reductase regulates vascular smooth muscle cell proliferation by modulating G1/S phase transition of cell cycle. Endocrinology, 2010, 151, 2140-2150.
[41]
Song, X.M.; Yu, Q.; Dong, X.; Yang, H.O.; Zeng, K.W.; Li, J.; Tu, P.F. Aldose reductase inhibitors attenuate β-amyloid-induced TNF-α production in microlgia via ROS-PKC-mediated NF-κB and MAPK pathways. Int. Immunopharmacol., 2017, 50, 30-37.
[42]
Reddy, A.B.; Ramana, K.V.; Srivastava, S.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase regulates high glucose-induced ectodomain shedding of tumor necrosis factor (TNF)-alpha via protein kinase C-delta and TNF-alpha converting enzyme in vascular smooth muscle cells. Endocrinology, 2009, 150, 63-74.
[43]
Demiot, C.; Tartas, M.; Fromy, B.; Abraham, P.; Saumet, J.L.; Sigaudo-Roussel, D. Aldose reductase pathway inhibition improved vascular and C-fiber functions, allowing for pressure-induced vasodilation restoration during severe diabetic neuropathy. Diabetes, 2006, 55, 1478-1483.
[44]
Ramana, K.V.; Chandra, D.; Srivastava, S.; Bhatnagar, A.; Srivastava, S.K. Aldose reductase mediates the mitogenic signals of cytokines. Chem. Biol. Interact., 2003, 143-144, 587-596.
[45]
Schmidt, R.E.; Dorsey, D.A.; Beaudet, L.N.; Plurad, S.B.; Parvin, C.A.; Yarasheski, K.E.; Smith, S.R.; Lang, H.J.; Williamson, J.R.; Ido, Y. Inhibition of sorbitol dehydrogenase exacerbates autonomic neuropathy in rats with streptozotocin-induced diabetes. J. Neuropathol. Exp. Neurol., 2001, 60, 1153-1169.
[46]
Obrosova, I.G.; Van Huysen, C.; Fathallah, L.; Cao, X.C.; Greene, D.A.; Stevens, M.J. An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. FASEB J., 2002, 16, 123-125.
[47]
Sellers, D.J.; Chess-Williams, R. The effects of streptozotocin-induced diabetes and aldose reductase inhibition with sorbinil, on left and right atrial function in the rat. J. Pharm. Pharmacol., 2000, 52, 687-694.
[48]
Rusak, T.; Misztal, T.; Rusak, M.; Branska-Januszewska, J.; Tomasiak, M. Involvement of hyperglycemia in the development of platelet procoagulant response: The role of aldose reductase and platelet swelling. Blood Coagul. Fibrinolysis, 2017, 28, 443-451.
[49]
Coppey, L.J.; Gellett, J.S.; Davidson, E.P.; Dunlap, J.A.; Yorek, M.A. Effect of treating streptozotocin-induced diabetic rats with sorbinil, myo-inositol or aminoguanidine on endoneurial blood flow, motor nerve conduction velocity and vascular function of epineurial arterioles of the sciatic nerve. Int. J. Exp. Diabetes Res., 2002, 3, 21-36.


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Article Details

VOLUME: 15
ISSUE: 1
Year: 2019
Page: [3 - 7]
Pages: 5
DOI: 10.2174/1573406414666180524082445
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