Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

Yıl 2013, Cilt: 2013 Sayı: 1, 94 - 98, 01.01.2013

Suat Kamışlı Arzu Karakurt Ayşe B. Uyumlu Basri Satılmış Abdullah Alagöz Metin F. Genç Kadir Batcıoğlu

https://doi.org/10.5152/balkanmedj.2012.067

Öz

Objective: Diabetic neuropathy (DN) is a common complication in Diabetes Mellitus. The streptozotocin-induced diabetic rodent is the most commonly used animal model of diabetes and increased sodium channel expression and activity were revealed in this model. At this study, we evaluated the effect of three different nafimidone derivatives which have possible anticonvulsant activity on disorders of thermal pain sensation in diabetic mice. Study Design: Randomized animal experiment. Material and Methods: Mice were divided randomly into five groups (5 mice per group): Control, Diabetes, Dibetes+C1, Diabetes+C2, Diabetes+C3. We used hot and cold plate, and tail-immersion tests for assessment of thermal nociceptive responses. Results: Compared with the control group, the hot-plate response time and the number of paw liftings on cold plate as important indicators of loss of sensation increased, but no significant difference (p>0.05) was found in tail-immersion response time test in diabetes group. C3 compound moved it back to control group levels in the all of three tests. C1 and C2 compounds were effective only in cold-plate test. Conclusion: Nafimidone derivatives may be effective in the cases where epilepsy and diabetes occur together since it has shown efficacy against “loss of sensation” which evolves in diabetic neuropathy over time as well as its antiepileptic effect. Turkish Başlık: Diabetik Nöropati Oluşturulmuş Farelerde Yeni Geliştirilmiş Nafimidone Türevlerinin Termal Hipoaljezi Üzerine Etkileri Anahtar Kelimeler: Diabet, Diabetik nöropati, Duyu kaybı, Antikonvülzanlar, Na kanal blokerleri, Nafimidon türevleri Amaç: Nöropati, diabetes mellitusun sık karşılaşılan komplikasyonudur ve periferik duyusal polinöropatinin ensık nedenidir. İlelemiş periferik polinöropati ise azalmış ısı duyarlılığı ile ilişkilidir. Bazı antikonvülzanların, diabetin neden olduğu nöropatinin tedavisindeki etkinliği deneysel ve klinik çalışmalarla gösterilmiştir. Bu çalışmada antikonvülzan etkinliği bilinen nafimidon'un üç farklı türevinin diabet oluşturulmuş farelerdeki termal hipoaljezi üzerine olan etkilerini araştırdık. Gereç ve Yöntemler: Fareler kontrol, diabetik, diabetik+C1, diabetik+C2, diabetik+C3 olmak üzere beşerli beş grub'a ayrıldı. Bütün gruplara, termal hipoaljeziyi değerlendirmek için hot-plate, cold-plate ve tail-immersion testleri uygulandı. Bulgular: Diabet ve kontrol grupları karşılaştırıldığında, termal hipoaljezinin önemli bir göstergesi olarak hot-plate ve cold-plate testindeki pençe çekme süresi ve sayısı diabet grubunda anlamlı ölçüde artış saptandı (p<0.005), tail-immersion süresinde anlamlı bir değişiklik saptanmadı (p˃0.05). C3 türevi, üç test sonucununda kontrol grubu değerlerine gelmesini sağladı, C1 ve C2 türevleri ise sadece cold-plate testinde etkili oldular. Sonuç: Bu çalışmadaki test sonuçları, nafimidon türevi antikonvülzanların diabetin neden olduğu termal hipoaljezinin önlenmesinde etkili oldukları ve bu bileşiklerin gelecekte potansiyel tedavi ajanları olarak kullanılabilecekleri yönünde destekleyici bulgular olarak yorumlandı.

Anahtar Kelimeler

Diabet, diabetic neuropathy, loss of sensation, antiepileptic, Na channel blocker, nafimidone derivatives

Evaluation of the Effects of Novel Nafimidone Derivatives on Thermal Hypoalgesia in Mice with Diabetic Neuropathy

Öz

Kaynakça

• Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Paciorek CJ, et al. National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980:systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet 2011;378:31-40. [CrossRef]
• Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 2004;25:612-28. [CrossRef]
• Oates PJ. Polyol pathway and diabetic peripheral neuropathy. Int Rev Neurobiol 2002;50:325-92. [CrossRef]
• Toth C, Rong LL, Yang C, Martinez J, Song F, Ramji N, et al. Receptor for advanced glycation end products (RAGEs) and experimental diabetic neuropathy. Diabetes 2008;57:1002-17. [CrossRef]
• Tomlinson DR. Mitogen-actiavated protein kinases as glucose transducers for diabetic complications. Diabetologia 1999;42:1271-81. [CrossRef]
• Chan L, Terashima T, Urabe H, Lin F, Kojima H. Pathogenesis of diabetic neuropathy:bad to the bone. Ann NY Acad Sci 2011;1240:70-6. [CrossRef]
• Konrad R, Mikolaenko I, Tolar J, Liu K, Kudlow J. The potential mechanism of the diabetogenic action of streptozotocin:Inhibition of pancreatic beta-cell O-GlcNAc-selective N-acetyl-b-D-glucosaminidase. Biochem J 2001;356:31-41. [CrossRef]
• Elsner M, Guldbakke B, Tiedge M, Munday R, Lenzen S. Relative importance of transport and alkylation for pancreatic b-cell toxicity of streptozotocin. Diabetologia 2000;43:1528-33. [CrossRef] Otto KJ, Wyse BD, Cabot PJ, Smith MT. Insulin implants prevent the temporal development of mechanical allodynia and opioid hyposensitivity for 24-wks in streptozotocin (stz)-diabetic wistar rats. Pain Med 2011;12:782-93. [CrossRef]
• Obrosova IG. Diabetic painful and insensate neuropathy:pathogenesis and potential treatments. Neurotherapeutics 2009;6:638-47. [CrossRef]
• Hong S, Wiley JW. Early painful diabetic neuropathy is associated with differential changes in tetrodotoxin-sensitive and -resistant sodium channels in dorsal root ganglion neurons in the rat. J Bio Chem 2004;279:29341-50.
• Catterall WA. Structural biology:A 3D view of sodium channels. Nature 2001;409:988-90. [CrossRef]
• Bhattacharya A, Wickenden AD, Chaplan SR. Sodium channel blockers for the treatment of neuropathic pain. Neurotherapeutics 2009;6:663-78. [CrossRef]
• Lai J, Hunter JC, Porreca F. The role of voltage-gated sodium channels in neuropathic pain. Curr Opin Neurobiol 2003;13:291-7. [CrossRef]
• Zuliani V, Rivara M, Fantini M, Costantino G. Sodium channel blockers for neuropathic pain. Expert Opin Ther Pat 2010;20:755-79. [CrossRef]
• Dalkara S, Karakurt A. Recent progress in anticonvulsant drug research:strategies for anticonvulsant drug development and applications of antiepileptic drugs for non-epileptic central nervous system disorders. Curr Top Med Chem 2012;12:1033-71. [CrossRef]
• Karakurt A, Özalp M, Işık Ş, Stables JP, Dalkara S. Synthesis, anticonvulsant and antimicrobial activities of some new 2-acetylnaphthalene derivatives. Bioorg Med Chem 2010;18:2902-11. [CrossRef]
• Karakurt A, Dalkara S, Özalp M, Özbey S, Kendi E, Stables JP. Synthesis of some 1-(2-naphthyl)-2-(imidazole-1-yl)ethanone oxime and oxime ether derivatives and their anticonvulsant and antimicrobial activities. Eur J Med Chem 2001;36:421-33. [CrossRef]
• Alagöz A. Studies on new (arylalkyl)imidazole compounds, synthesis and anticonvulsant activities. Master Thesis of Inonu University, Health Sciences Institute, Department of Pharmaceutical Chemistry, 2011.
• Dan M, Chantler JK. A novel pancreatropic coxsackievirus vector expressing glucagon-like peptide 1 reduces hyperglycemia in streptozotocin-treated mice. J Virol 2011;85:12759-68. [CrossRef]
• Bispo MD, Mourao RHV, Franzotti EM, Bomfim KBR, Arrigoni-Blank MF, Moreno MPN, et al. Antinociceptive and antiedematogenic effects of the aqueous extract of Hyptis pectinata leaves in experimental animals. J Ethnopharmacol 2001;76:81-6. [CrossRef]
• Nainwal P, Kalra K, Nanda D, Singh A. Study of analgesic and anti-inflammatory activities of the ethanolic extract arial parts of Fumaria Vaillantii Loisel. Asian J Pharm Clin Res 2011;4:90-1.
• Ahmadi A, Khalili M, Mihandoust F, Barghi L. Synthesis and determination of acute and chronic pain activities of 1-(1-(3-methylphenyl)-(tetralyl))piperidine as a new derivative of phencyclidine via tail immersion and formalin tests. Arzneimittelforschung 2010;60:30-5.
• Berrocoso E, De Benito MD, Mico JA. Role of serotonin 5-HT1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats. Psychopharmacology (Berl) 2007;193:97-105. [CrossRef]
• Jasmin L, Kohan L, Franssen M, Janni G, Goff JR. The cold plate as a test of nociceptive behaviors:description and application to the study of chronic neuropathic and inflammatory pain models. Pain 1998;75:367-82. [CrossRef]
• Haranishi Y, Hara K, Terada T, Nakamura S, Sata T. The antinociceptive effect of intrathecal administration of glycine transporter-2 inhibitor ALX1393 in a rat acute pain model. Anesth Analg 2010;110:615-21. [CrossRef]
• Yasuda H, Terada M, Maeda K, Kogawa S, Sanada M, Haneda M, et al. Diabetic neuropathy and nerve regeneration. Prog Neurobiol 2003;69:229-85. [CrossRef]
• Kamiya H, Zhang W, Sima AA. Degeneration of the Golgi and neuronal loss in dorsal root ganglia in diabetic BioBreeding/ Worcester rats. Diabetologia 2006;49:2763-74. [CrossRef]
• Biessels GJ, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW, et al. Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats. Diabetes 1996;45:1259-66. [CrossRef]
• Andriambeloson E, Baillet C, Vitte PA, Garotta G, Dreano M, Callizot N. Interleukin-6 attenuates the development of experimental diabetes-related neuropathy. Neuropathology 2006;26:32-42. [CrossRef]
• Drel VR, Mashtalir N, Ilnytska O, Shin J, Li F, Lyzogubov VV, et al. The leptin-deficient (ob/ob) mouse:a new animal model of peripheral neuropathy of type 2 diabetes and obesity. Diabetes 2006;55:3335-43. [CrossRef]
• Obrosova IG, Ilnytska O, Lyzogubov VV, Pavlov IA, Mashtalir N, Nadler JL, et al. High-fat diet induced neuropathy of pre-diabetes and obesity:effects of “healthy” diet and aldose reductase inhibition. Diabetes 2007;56:2598-608. [CrossRef]
• Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001;414:813-820. [CrossRef]
• Misawa S, Sakurai K, Shibuya K, Isose S, Kanai K, Ogino J, et al. Neuropathic pain is associated with increased nodal persistent Na(+) currents in human diabetic neuropathy. J Peripher Nerv Syst 2009;14:279-84. [CrossRef]
• Aldrich RW, Corey DP, Stevens CF. A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature 1983;306:436-41. [CrossRef]
• Gold MS. Na+ channel blockers for the treatment of pain:context is everything, almost. Exp Neurol 2008;210:1-6. [CrossRef]
• Weston RM, Subasinghe KR, StaikopoulosV, Jarrott B. Design and assessment of a potent sodium channel blocking derivative of mexiletine for minimizing experimental neuropathic pain in several rat models. Neurochem Res 2009;34:1816-23. [CrossRef] Khan S, Zhou L. Characterization of non-length-dependent smallfiber sensory neuropathy. Muscle Nerve 2012;45:86-91. [CrossRef] Oskarsson P, Ljunggren JG, Lins PE. Efficacy and safety of mexiletine in the treatment of painful diabetic neuropathy. The mexiletine study group. Diabetes Care 1997;20:1594-7. [CrossRef]
• Tesfaye S, Selvarajah D. Advances in the epidemiology, pathogenesis and management of diabetic peripheral neuropathy. Diabetes-Metab Res 2012;28:8-14. [CrossRef]