Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats

Overview

Journal Int J Impot Res

Specialties Reproductive Medicine
Urology

Date 2018 Sep 15

PMID 30214006

Citations 5

Authors

Bai-Bing Yang

Zhi-Wei Hong

Zheng Zhang

Wen Yu

Tao Song

Lei-Lei Zhu

He-Song Jiang

Guo-Tao Chen

Yun Chen

Yu-Tian Dai

Affiliations

Soon will be listed here.

Abstract

Epalrestat, an aldose reductase inhibitor (ARI), was adopted to improve the function of peripheral nerves in diabetic patients. The aim of this study was to investigate whether epalrestat could restore the erectile function of diabetic erectile dysfunction using a rat model. From June 2016, 24 rats were given streptozocin (STZ) to induce the diabetic rat model, and epalrestat was administered to ten diabetic erectile dysfunction (DED) rats. Intracavernous pressure (ICP) and mean systemic arterial pressure (MAP), levels of aldose reductase (AR), nerve growth factor (NGF), neuronal nitric oxide synthase (nNOS), α-smooth muscle antigen (α-SMA), and von Willebrand factor (vWF) in the corpus cavernosum were analyzed. We discovered that epalrestat acted on cavernous tissue and partly restored erectile function. NGF and nNOS levels in the corpora were increased after treatment with epalrestat. We also found that the content of α-SMA-positive smooth muscle cells and vWF-positive endothelial cells in the corpora cavernosum were declined. Accordingly, epalrestat might improve erectile function by increasing the upregulation of NGF and nNOS to restore the function of the dorsal nerve of the penis.

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References

Kikkawa R, Hatanaka I, Yasuda H, Kobayashi N, Shigeta Y, Terashima H . Effect of a new aldose reductase inhibitor, (E)-3-carboxymethyl-5-[(2E)-methyl-3-phenylpropenylidene]rhodanine (ONO-2235) on peripheral nerve disorders in streptozotocin-diabetic rats. Diabetologia. 1983; 24(4):290-2. DOI: 10.1007/BF00282716. View

Bivalacqua T, Usta M, Champion H, Kadowitz P, Hellstrom W . Endothelial dysfunction in erectile dysfunction: role of the endothelium in erectile physiology and disease. J Androl. 2003; 24(6 Suppl):S17-37. DOI: 10.1002/j.1939-4640.2003.tb02743.x. View

Vlassara H, Fuh H, Makita Z, Krungkrai S, Cerami A, Bucala R . Exogenous advanced glycosylation end products induce complex vascular dysfunction in normal animals: a model for diabetic and aging complications. Proc Natl Acad Sci U S A. 1992; 89(24):12043-7. PMC: 50694. DOI: 10.1073/pnas.89.24.12043. View

Calcutt N, Freshwater J, Hauptmann N, Taylor E, Mizisin A . Protection of sensory function in diabetic rats by Neotrofin. Eur J Pharmacol. 2006; 534(1-3):187-93. DOI: 10.1016/j.ejphar.2006.01.047. View

Hotta N, Kawamori R, Fukuda M, Shigeta Y . Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on progression of diabetic neuropathy and other microvascular complications: multivariate epidemiological analysis based on patient background factors and severity of diabetic.... Diabet Med. 2012; 29(12):1529-33. PMC: 3533175. DOI: 10.1111/j.1464-5491.2012.03684.x. View

Burnett A, Lue T . Neuromodulatory therapy to improve erectile function recovery outcomes after pelvic surgery. J Urol. 2006; 176(3):882-7. DOI: 10.1016/j.juro.2006.04.020. View

Steele J, Faulds D, Goa K . Epalrestat. A review of its pharmacology, and therapeutic potential in late-onset complications of diabetes mellitus. Drugs Aging. 1993; 3(6):532-55. DOI: 10.2165/00002512-199303060-00007. View

Chen Y, Yang R, Yao L, Sun Z, Wang R, Dai Y . Differential expression of neurotrophins in penises of streptozotocin-induced diabetic rats. J Androl. 2006; 28(2):306-12. DOI: 10.2164/jandrol.106.000794. View

Chen K, Chan J, Chang L, Chen M, Chan S . Intracavernous pressure as an experimental index in a rat model for the evaluation of penile erection. J Urol. 1992; 147(4):1124-8. DOI: 10.1016/s0022-5347(17)37500-6. View

10.

Hamada Y, Nakamura J . Clinical potential of aldose reductase inhibitors in diabetic neuropathy. Treat Endocrinol. 2005; 3(4):245-55. DOI: 10.2165/00024677-200403040-00006. View

11.

Hotta N, Sakamoto N, Shigeta Y, Kikkawa R, Goto Y . Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan. J Diabetes Complications. 1996; 10(3):168-72. DOI: 10.1016/1056-8727(96)00113-4. View

12.

De Young L, Domes T, Lim K, Carson J, Brock G . Endothelial rehabilitation: the impact of chronic PDE5 inhibitors on erectile function and protein alterations in cavernous tissue of diabetic rats. Eur Urol. 2008; 54(1):213-20. DOI: 10.1016/j.eururo.2008.02.034. View

13.

Hayashi R, Hayakawa N, Makino M, Nagata M, Kakizawa H, Uchimura K . Changes in erythrocyte sorbitol concentrations measured using an improved assay system in patients with diabetic complications and treated with aldose reductase inhibitor. Diabetes Care. 1998; 21(4):672-3. DOI: 10.2337/diacare.21.4.672. View

14.

Baba M, Kimura K, Suda T, Yagihashi S . Three-year inhibition of aldose reductase on development of symptomatic neuropathy in diabetic patients. J Peripher Nerv Syst. 2006; 11(2):176-8. DOI: 10.1111/j.1085-9489.2006.00085.x. View

15.

McHugh K . Molecular analysis of smooth muscle development in the mouse. Dev Dyn. 1995; 204(3):278-90. DOI: 10.1002/aja.1002040306. View

16.

Ramirez M, Borja N . Epalrestat: an aldose reductase inhibitor for the treatment of diabetic neuropathy. Pharmacotherapy. 2008; 28(5):646-55. DOI: 10.1592/phco.28.5.646. View

17.

Suzuki T, Sekido H, Kato N, Nakayama Y, Yabe-Nishimura C . Neurotrophin-3-induced production of nerve growth factor is suppressed in Schwann cells exposed to high glucose: involvement of the polyol pathway. J Neurochem. 2004; 91(6):1430-8. DOI: 10.1111/j.1471-4159.2004.02824.x. View

18.

Ohi T, Saita K, Furukawa S, Ohta M, Hayashi K, Matsukura S . Therapeutic effects of aldose reductase inhibitor on experimental diabetic neuropathy through synthesis/secretion of nerve growth factor. Exp Neurol. 1998; 151(2):215-20. DOI: 10.1006/exnr.1998.6821. View

19.

Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M . Long-term clinical effects of epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy: the 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial. Diabetes Care. 2006; 29(7):1538-44. DOI: 10.2337/dc05-2370. View

20.

Terashima H, Hama K, Yamamoto R, Tsuboshima M, Kikkawa R, Hatanaka I . Effects of a new aldose reductase inhibitor on various tissues in vitro. J Pharmacol Exp Ther. 1984; 229(1):226-30. View