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Mirtazapin Diyabet Oluşturulan Sıçanların Beyinciklerindeki Hasarı Kısmen Düzeltmektedir

Yıl 2018, Cilt: 40 Sayı: 3, 61 - 69, 01.09.2018
https://doi.org/10.20515/otd.394800

Öz

Diabetes mellitus sistemik bir
hastalık olup çeşitli organlarda hasara neden olmaktadır. Bu organlar arasında beyincik
de yer almaktadır. Mirtazapin ise majör depresyon tedavisinde kullanılan bir
antidepresan madde olup inflamasyon yanıtının düzenlenmesinde de rol
oynamaktadır.
 Bütün bu bilgiler ışığında, çalışmamızda DM oluşturulan sıçanların
beyinciklerinde meydana gelen değişiklikleri ve bu değişiklikler üzerine
mirtazapinin etkilerini araştırmayı amaçladık.
Çalışmamızda toplam 21 adet yetişkin, erkek Sprague Dawley sıçan 3 eşit gruba
ayrıldı (n=7). Kontrol grubuna hiçbir uygulama yapılmadı. DM grubundaki hayvanlara
tek doz 55 mg/kg streptozotosin intraperitoneal olarak verilerek DM
oluşturuldu. Mirtazapin grubuna streptozotosin uygulamasından 28 gün sonra, 14
gün boyunca günde 20 mg/kg mirtazapin
gavaj yoluyla uygulandı. Deney sonunda
alınan beyincik örnekleri %10’luk formaldehit ile fikse edildikten sonra rutin doku
takip işleminin ardından alınan kesitlere hematoksilen ve eozin, krezil viyole boyama
teknikleri ve akson rejenerasyonunu belirlemek amacıyla da GAP-43
immünohistokimyasal boyaması uygulandı.
Kontrol grubunda beyincikte normal histoloji
ile medüllada yüksek GAP-43 ekspresyonu gözlendi. DM grubunda Purkinje
nöronlarında büzüşme ve bazı alanlarda hücre ölümü saptanırken, orta düzeyde GAP-43
immünoreaksiyonu belirlendi. Mirtazapin uygulanan grupta ise Purkinje nöronlarının
ve histolojik yapının kontrol grubuna yakın olduğu gözlenirken GAP-43 ekspresyonunun
DM grubuna benzer olduğu saptandı.
Sonuç olarak, streptozotosinle oluşturulan DM
sıçanların beyinciğinde özellikle Purkinje nöronlarında hasara ve medüllada
miyelin kaybına yol açmakta ve mirtazapin uygulaması Purkinje nöronlarındaki hasarı
azaltmakta, ancak miyelin rejenerasyonunu sağlamada belirgin bir etki göstermemektedir.

Kaynakça

  • Baydas G, Nedzvetskii VS, Tuzcu M, Yasar A, Kirichenko SV. Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E. European journal of pharmacology. 2003;462(1):67-71.
  • Baydas G, Reiter RJ, Yasar A, Tuzcu M, Akdemir I, Nedzvetskii VS. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free Radical Biology and Medicine. 2003;35(7):797-804.
  • Gispen WH, Biessels G-J. Cognition and synaptic plasticity in diabetes mellitus. Trends in neurosciences. 2000;23(11):542-549.
  • Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Frontiers in cellular neuroscience. 2014;8:355
  • Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends in neurosciences. 2001;24(8):450-455.
  • Lai FYX, Shankar K, Ritz S. Mirtazapine-associated peripheral oedema. Australian and New Zealand Journal of Psychiatry. 2016;50(11):1108-1112
  • Ozogula B, Kisaoglua A, Turanb MI, Altunerc D, Senerd E, Cetine N, et al. The effect of mirtazapine on methotrexate-induced toxicity in rat liver. Science Asia. 2013;39:356-362.
  • Carriel V, Garzón I, Campos A, Cornelissen M, Alaminos M. Differential expression of GAP‐43 and neurofilament during peripheral nerve regeneration through bio‐artificial conduits. Journal of tissue engineering and regenerative medicine. 2017;11(2):553-563.
  • Hernández-Fonseca JP, Rincón J, Pedreañez A, Viera N, Arcaya JL, Carrizo E, et al. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats. Experimental Diabetes Research. 2009; Article ID 329632
  • Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012;83(4):650-659.
  • Liu X, Zhang G, Dong L, Wang X, Sun H, Shen J, et al. Repeated administration of mirtazapine attenuates oxaliplatin-induced mechanical allodynia and spinal NR2B up-regulation in rats. Neurochemical research. 2013;38(9):1973-1979.
  • Erem C, İmamoğlu Hİ. Tip-1 Diyabet Hastalarında Serum Karbonik Anhidraz I-II Otoantikor Düzeyleri ile Diyabetik Retinopati Arasındaki İlişki. 2017;47:85-88.
  • Yan Y, Hartono S, Hennedige T, Koh T, Chan C, Zhou L, et al. Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes. Magnetic resonance imaging. 2017;38:71-76.
  • Biessels GJ, ter Laak MP, Kamal A, Gispen WH. Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats. Brain Research. 2005;1035(1):86-93.
  • Atif F, Prunty MC, Turan N, Stein DG, Yousuf S. Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve. Neuroscience. 2017;350:1-12.
  • Kara A, Unal D, Simsek N, Yucel A, Yucel N, Selli J. Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study. Gynecological Endocrinology. 2014;30(3):226-231.
  • Iwasaki H, Sato R, Shichiri M, Hirata Y. A patient with type 1 diabetes mellitus and cerebellar ataxia associated with high titer of circulating anti-glutamic acid decarboxylase antibodies. Endocrine journal. 2001;48(2):261-268.
  • Özdemir NG, Akbaş F, Kotil T, Yilmaz A. Analysis of diabetes-related cerebellar changes in streptozotocin-induced diabetic rats. Turkish journal of medical sciences. 2016; 46(5):1579-1592.
  • Sherif RN. Effect of cerebrolysin on the cerebellum of diabetic rats: An imunohistochemical study. Tissue & cell. 2017;49(6):726-733.
  • David JA, Rifkin WJ, Rabbani PS, Ceradini DJ. The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. Journal of Diabetes Research. 2017; Article ID 4826724.
  • Bursova S, Dubovy P, Vlckova-Moravcova E, Nemec M, Klusakova I, Belobradkova J, et al. Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus. Journal of the Neurological Sciences. 2012;315(1):60-63.
  • Demir E, Yilmaz Ö. Streptozotosin ile tip-2 diyabet oluşturulan sıçanlarda çam yağının antihiperglisemik ve bazı biyokimyasal parametrelere etkisi. Marmara Fen Bilimleri Dergisi. 2013;25(3):140-156.
  • El-Sisi AE, El-Sayad ME, Abdelsalam NM. Protective effects of mirtazapine and chrysin on experimentally induced testicular damage in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017;95:1059-1066.
  • Khedr NF. Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries. Experimental biology and medicine (Maywood, NJ). 2015;240(12):1682-1689.
  • Tok A, Sener E, Albayrak A, Cetin N, Polat B, Suleyman B, et al. Effect of mirtazapine on oxidative stress created in rat kidneys by ischemia-reperfusion. Renal failure. 2012;34(1):103-110.
  • Zhu J, Wei X, Feng X, Song J, Hu Y, Xu J. Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-kappaB in a rat model of neuropathic pain. Neuroscience letters. 2008;433(1):33-37.
  • Altuner D, Gulaboglu M, Yapca OE, Cetin N. The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries. The Scientific World Journal. 2013; Article ID 327240.
  • Fang C-K, Chen H-W, Chiang I-T, Chen C-C, Liao J-F, Su T-P, et al. Mirtazapine inhibits tumor growth via immune response and serotonergic system. PLoS One. 2012;7(7):e38886.

Mirtazapine Partially Ameliorate Damage of the Diabetic Rat Cerebellum

Yıl 2018, Cilt: 40 Sayı: 3, 61 - 69, 01.09.2018
https://doi.org/10.20515/otd.394800

Öz

Diabetes mellitus is a systemic
disease that causes damage to various organs. Among these organs, cerebellum is
also present. Mirtazapine is an antidepressant used in the treatment of major
depression also regulating the inflammatory response. With all this
information, we aimed to investigate the effects of DM on rat cerebellum and
effects of mirtazapine on DM-induced cerebellum damage. In our study 21 adult, male,
Sprague Dawley rats were equaly
divided into 3 groups (n = 7). No treatment was made to the control group.
Animals in the DM group received a single dose of 55 mg/kg streptozotocin
intraperitoneally. Mirtazapine was administered via gavage 20 mg / kg
mirtazapine daily for 14 days after 28 days of streptozotocin administration.
After 28 days of streptozotin administration 20 mg / kg mirtazapine was
administered to the mirtazapine group via gavage per day for 14 days. At the
end of the experiment, cerebellum specimens were fixed with 10% formaldehyde,
following routine tissue processing hematoxylin-eosin, krezil violet dyeing
techniques and GAP-43 immunohistochemical staining made to determine axonal
regeneration. The control group had high GAP-43 expression in medullary with
normal histology in the cerebellum. Moderate GAP-43 immunoreactivity, cell
death in some areas and shrinkage of Purkinje neurons was detected in the DM
group. In the mirtazapine group, Purkinje neurons were found to protect normal
structures relatively better, while GAP-43 expression was found to be similar
to the DM group. As a result, streptozotocin-induced DM leads to loss of myelin
in the brain, especially in Purkinje neurons damage, and mirtazapine
administration, which reduces damage in the Purkinje neurons, but does not have
a significant effect on myelin regeneration.

Kaynakça

  • Baydas G, Nedzvetskii VS, Tuzcu M, Yasar A, Kirichenko SV. Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E. European journal of pharmacology. 2003;462(1):67-71.
  • Baydas G, Reiter RJ, Yasar A, Tuzcu M, Akdemir I, Nedzvetskii VS. Melatonin reduces glial reactivity in the hippocampus, cortex, and cerebellum of streptozotocin-induced diabetic rats. Free Radical Biology and Medicine. 2003;35(7):797-804.
  • Gispen WH, Biessels G-J. Cognition and synaptic plasticity in diabetes mellitus. Trends in neurosciences. 2000;23(11):542-549.
  • Nagayach A, Patro N, Patro I. Experimentally induced diabetes causes glial activation, glutamate toxicity and cellular damage leading to changes in motor function. Frontiers in cellular neuroscience. 2014;8:355
  • Watkins LR, Milligan ED, Maier SF. Glial activation: a driving force for pathological pain. Trends in neurosciences. 2001;24(8):450-455.
  • Lai FYX, Shankar K, Ritz S. Mirtazapine-associated peripheral oedema. Australian and New Zealand Journal of Psychiatry. 2016;50(11):1108-1112
  • Ozogula B, Kisaoglua A, Turanb MI, Altunerc D, Senerd E, Cetine N, et al. The effect of mirtazapine on methotrexate-induced toxicity in rat liver. Science Asia. 2013;39:356-362.
  • Carriel V, Garzón I, Campos A, Cornelissen M, Alaminos M. Differential expression of GAP‐43 and neurofilament during peripheral nerve regeneration through bio‐artificial conduits. Journal of tissue engineering and regenerative medicine. 2017;11(2):553-563.
  • Hernández-Fonseca JP, Rincón J, Pedreañez A, Viera N, Arcaya JL, Carrizo E, et al. Structural and Ultrastructural Analysis of Cerebral Cortex, Cerebellum, and Hypothalamus from Diabetic Rats. Experimental Diabetes Research. 2009; Article ID 329632
  • Kandhare AD, Raygude KS, Ghosh P, Ghule AE, Bodhankar SL. Neuroprotective effect of naringin by modulation of endogenous biomarkers in streptozotocin induced painful diabetic neuropathy. Fitoterapia. 2012;83(4):650-659.
  • Liu X, Zhang G, Dong L, Wang X, Sun H, Shen J, et al. Repeated administration of mirtazapine attenuates oxaliplatin-induced mechanical allodynia and spinal NR2B up-regulation in rats. Neurochemical research. 2013;38(9):1973-1979.
  • Erem C, İmamoğlu Hİ. Tip-1 Diyabet Hastalarında Serum Karbonik Anhidraz I-II Otoantikor Düzeyleri ile Diyabetik Retinopati Arasındaki İlişki. 2017;47:85-88.
  • Yan Y, Hartono S, Hennedige T, Koh T, Chan C, Zhou L, et al. Intravoxel incoherent motion and diffusion tensor imaging of early renal fibrosis induced in a murine model of streptozotocin induced diabetes. Magnetic resonance imaging. 2017;38:71-76.
  • Biessels GJ, ter Laak MP, Kamal A, Gispen WH. Effects of the Ca2+ antagonist nimodipine on functional deficits in the peripheral and central nervous system of streptozotocin-diabetic rats. Brain Research. 2005;1035(1):86-93.
  • Atif F, Prunty MC, Turan N, Stein DG, Yousuf S. Progesterone modulates diabetes/hyperglycemia-induced changes in the central nervous system and sciatic nerve. Neuroscience. 2017;350:1-12.
  • Kara A, Unal D, Simsek N, Yucel A, Yucel N, Selli J. Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study. Gynecological Endocrinology. 2014;30(3):226-231.
  • Iwasaki H, Sato R, Shichiri M, Hirata Y. A patient with type 1 diabetes mellitus and cerebellar ataxia associated with high titer of circulating anti-glutamic acid decarboxylase antibodies. Endocrine journal. 2001;48(2):261-268.
  • Özdemir NG, Akbaş F, Kotil T, Yilmaz A. Analysis of diabetes-related cerebellar changes in streptozotocin-induced diabetic rats. Turkish journal of medical sciences. 2016; 46(5):1579-1592.
  • Sherif RN. Effect of cerebrolysin on the cerebellum of diabetic rats: An imunohistochemical study. Tissue & cell. 2017;49(6):726-733.
  • David JA, Rifkin WJ, Rabbani PS, Ceradini DJ. The Nrf2/Keap1/ARE Pathway and Oxidative Stress as a Therapeutic Target in Type II Diabetes Mellitus. Journal of Diabetes Research. 2017; Article ID 4826724.
  • Bursova S, Dubovy P, Vlckova-Moravcova E, Nemec M, Klusakova I, Belobradkova J, et al. Expression of growth-associated protein 43 in the skin nerve fibers of patients with type 2 diabetes mellitus. Journal of the Neurological Sciences. 2012;315(1):60-63.
  • Demir E, Yilmaz Ö. Streptozotosin ile tip-2 diyabet oluşturulan sıçanlarda çam yağının antihiperglisemik ve bazı biyokimyasal parametrelere etkisi. Marmara Fen Bilimleri Dergisi. 2013;25(3):140-156.
  • El-Sisi AE, El-Sayad ME, Abdelsalam NM. Protective effects of mirtazapine and chrysin on experimentally induced testicular damage in rats. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2017;95:1059-1066.
  • Khedr NF. Protective effect of mirtazapine and hesperidin on cyclophosphamide-induced oxidative damage and infertility in rat ovaries. Experimental biology and medicine (Maywood, NJ). 2015;240(12):1682-1689.
  • Tok A, Sener E, Albayrak A, Cetin N, Polat B, Suleyman B, et al. Effect of mirtazapine on oxidative stress created in rat kidneys by ischemia-reperfusion. Renal failure. 2012;34(1):103-110.
  • Zhu J, Wei X, Feng X, Song J, Hu Y, Xu J. Repeated administration of mirtazapine inhibits development of hyperalgesia/allodynia and activation of NF-kappaB in a rat model of neuropathic pain. Neuroscience letters. 2008;433(1):33-37.
  • Altuner D, Gulaboglu M, Yapca OE, Cetin N. The effect of mirtazapine on cisplatin-induced oxidative damage and infertility in rat ovaries. The Scientific World Journal. 2013; Article ID 327240.
  • Fang C-K, Chen H-W, Chiang I-T, Chen C-C, Liao J-F, Su T-P, et al. Mirtazapine inhibits tumor growth via immune response and serotonergic system. PLoS One. 2012;7(7):e38886.
Toplam 28 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm ORİJİNAL MAKALELER / ORIGINAL ARTICLES
Yazarlar

Erhan Şahin

Ezgi Bektur Bu kişi benim

Dilek Burukoğlu Dönmez

Cengiz Bayçu Bu kişi benim

Devrim Özgür Can

Varol Şahintürk

Yayımlanma Tarihi 1 Eylül 2018
Yayımlandığı Sayı Yıl 2018 Cilt: 40 Sayı: 3

Kaynak Göster

Vancouver Şahin E, Bektur E, Burukoğlu Dönmez D, Bayçu C, Özgür Can D, Şahintürk V. Mirtazapin Diyabet Oluşturulan Sıçanların Beyinciklerindeki Hasarı Kısmen Düzeltmektedir. Osmangazi Tıp Dergisi. 2018;40(3):61-9.


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