PİNEALEKTOMİLİ RATLARIN BEYİN DOKUSUNDA AKRİLAMİD İLE OLUŞTURULAN NÖROTOKSİSİTE ÜZERİNE EKZOJEN MELATONİNİN KORUYUCU ETKİLERİNİN ARAŞTIRILMASI
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2022-06
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info:eu-repo/semantics/openAccess
Özet
Akrilamid oda sıcaklığında, kokusuz, beyaz, katı kristal bir yapıya sahiptir. Suda çözünürlüğü yüksek olan, polar çözücülerde iyi çözünürken, polar olmayan çözücülerde ise çok az çözünen kimyasal bir maddedir. Doğada serbest olarak bulunmayıp kimyasal yollarla sentezlenir. Akrilamid, karbonhidrat açısından zengin gıdaların yüksek sıcaklıklarda veya diğer termal işlemlerde hazırlanması nedeniyle oluşan toksik bir kimyasal kanserojendir. Akrilamid toksik kimyasal bir madde olması sebebiyle reprodüktif sistemi etkilemekle birlikte ayrıca genotoksik, karsinojenik, ve nörotoksik etkileri bulunmaktadır. Akrilamidin özellikle nörotoksisite alanındaki araştırmaları büyük ilgi görmüştür. Akrilamid insanlarada olduğu kadar ratlarda da nörolojik bozuklukların ciddiyeti ve semptomların ilerlemesinin doz hızı ve konsantrasyonuna bağlı olarak alınan doz miktarına göre nöropatiye sebep olduğu hatta artan dozlarda ölümcül olduğu görülmüştür. Memelilerin pineal bezinden salgılanan ve çeşitli sirkadiyen ritimleri düzenleyen melatonin hormonunun, nöroprotektif etki, anti-amiloid etki, antilipidemik, antihipertansif ve antioksidan savunma gibi fizyolojik ve metabolik olaylarda önemli rol oynamaktadır. Ayrıca serbest radikal süpürücü özelliğinin keşfinden sonra yapılan araştırmalar sonucu radikallerin detoksifikasyonunda işlev gördüğünde oluşan metabolitleri de radikal süpürücü özelliktedir. Çalışmamızda, ratlara pinealektomi işlemi uygulanarak melatonin yoksunluğu oluşturuldu. Ardından pinealektomi ve Sham pinealektomi uygulanan ratlar, art arda 21 gün boyunca tek başına veya eksojen melatonin (10 mg/kg vücut ağırlığı, i.p.) varlığında akrilamide (25 mg/kg vücut ağırlığı, ağızdan) maruz bırakıldı. Böylelikle Wistar albino ratların beyin/beyincik dokusundaki oksidatif stres belirteçlerini ve serum melatonin düzeylerini ayrıca histopatolojik ve beyin/beyincik dokusunun immünohistokimyasal değerlendirmeleri göz önünde bulundurularak, akrilamid ile kombine edilmiş eksojen melatonin tedavisinin nörotoksisite üzerindeki olası etkilerini ve akrilamid kaynaklı nörotoksisitesinin olası rolünü değerlendirmeyi amaçladık. Bu amaçla altmış rat Sham ve pinealektomi olmak üzere iki ana gruba ayrıldıktan sonra bu iki ana grupta kendi içlerinde üçer gruba ayrıldı; (a) Sham (%0,5 ‘lik etanol çözeltisinden 21 gün boyunca i.p olarak uygulandı), (b) Sham+AKR grubu (deney süresince 25 mg/kg/gün akrilamid olacak şekilde 21 gün boyunca gavajla verildi), (c) Sham+AKR+MLT (deney süresince akrilamid 25 mg/kg/gün olacak şekilde 21 gün boyunca gavajla, melatonin ise 10 mg/kg/gün olacak şekilde 21 gün boyunca 0,5 ml hacminde i.p olarak uygulandı), (d) PINX grubu (Epifiz bezi pinealaktomi ile çıkarıldıktan sonra deney süresince 21 gün boyunca i.p olarak %0,5 ‘lik etanol çözeltsi uygulandı) (e) PINX + AKR grubu (Epifiz bezi pinealaktomi ile çıkarıldıktan sonra deney süresince 21 gün boyunca i.p olarak %0,5 ‘lik etanol çözeltisi, 21 gün boyunca 25 mg/kg/gün akrilamid olacak şekilde gavajla uygulandı), (f) PINX+AKR+MLT (Epifiz bezi pinealaktomi ile çıkarıldıktan sonra deney süresince 21 gün boyunca i.p olarak %0,5 ‘lik etanol çözeltisi, 21 gün boyunca 25 mg/kg/gün akrilamid olacak şekilde gavajla, melatonin ise 21 gün boyunca 10 mg/kg/gün olacak şekilde uygulandı). Çalışmamıza göre pinealektomize ratlarda akrilamide maruz kalma sırasında beyin oksidan/antioksidan durumu, inflamatuar mediatörler ve apoptoz değişiklikleri, pinealektomize olmayan ratlardan daha fazlaydı. Ayrıca, akrilamid uygulamasından sonra pinealektomize ratların beyin dokusunda histopatolojik değişiklikler daha fazlaydı. Eksojen melatonin tedavisi, süperoksit dismutaz (SOD) ve katalaz (CAT) gibi antioksidan enzimlerin aktivitelerini arttırdı ve beyin toplam antioksidan durumunu (TAS) iyileştirdi. Ayrıca melatonin, akrilamide maruz kalmış beyin dokularında lipid peroksidasyonunu, inflamatuar yolları ve apoptozu baskılamıştır. Ek olarak, akrilamide maruz kalmış ratlara eksojen melatonin müdahalesi, nöronal dokuların yapısını önemli ölçüde onarmıştır. Sonuç olarak, bu çalışma ilk kez ekzojen melatonin tedavisinin antioksidan enzimlerin aktivitelerini artırarak, lipid peroksidasyonunu ve inflamasyonu inhibe ederek ve akrilamid uygulamasından sonra pinealektomize ratların beyin dokusundaki histopatolojik değişiklikleri iyileştirerek oksidatif hasarı azaltabileceğini öne sürdü.
Acrylamide is a chemical substance with high solubility in water, soluble well in polar solvents, and very slightly soluble in non-polar solvents. It is not found freely in nature and is synthesized by chemical means. Acrylamide is a toxic chemical carcinogen formed due to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. Since acrylamide is a toxic chemical substance, it affects the reproductive system, but also has genotoxic, carcinogenic, and neurotoxic effects. Acrylamide's researches, especially in the field of neurotoxicity, have received great attention. It has been observed that acrylamide causes neuropathy in rats as well as in humans depending on the dose rate and concentration of the severity of neurological disorders and the progression of symptoms, and even fatal at increasing doses. The hormone melatonin, which is secreted from the pineal gland of mammals and regulates various circadian rhythms, plays an important role in physiological and metabolic events such as neuroprotective effect, anti-amyloid effect, antilipidemic, antihypertensive and antioxidant defense. In addition, as a result of the research carried out after the discovery of its free radical scavenging feature, its metabolites formed when it functions in the detoxification of radicals also have radical scavenging properties. In our study, melatonin deprivation was created by applying pinealectomy to rats. Subsequently, rats undergoing pinealectomy and Sham pinealectomy were exposed to acrylamide (25 mg/kg body weight, orally) alone or in the presence of exogenous melatonin (10 mg/kg body weight, i.p.) for 21 consecutive days. Thus, we aimed to evaluate the possible effects of exogenous melatonin combined with acrylamide on neurotoxicity and the possible role of acrylamide-induced neurotoxicity, considering the oxidative stress markers and serum melatonin levels in the brain/cerebellum tissue of Wistar albino rats, as well as the histopathological and immunohistochemical evaluations of the brain/cerebellum tissue. For this purpose, after sixty rats were divided into two main groups as Sham and pinealectomy, they were divided into three groups in each of these two main groups; (a) Sham (0.5% ethanol solution administered i.p. for 21 days), (b) Sham+AKR group (25 mg/kg/day acrylamide was given by gavage for 21 days during the experiment), (c) Sham+AKR+MLT (acrylamide 25 mg/kg/day was administered by gavage for 21 days, melatonin 10 mg/kg/day was administered as ip for 21 days in 0.5 ml volume during the experiment), (d) PINX group (After the pineal gland was removed by pinealactomy, 0.5% ethanol solution was applied i.p for 21 days during the experiment) (e) PINX + AKR group (after the pineal gland was removed by pinealactomy, i.p for 21 days during the experiment) 0.5% ethanol solution was gavaged at 25 mg/kg/day acrylamide for 21 days), (f) PINX+AKR+MLT (After pineal gland removal by pinealactomy, 0% i.p. for 21 days during the experiment. A 5% ethanol solution was administered by gavage at 25 mg/kg/day acrylamide for 21 days, and melatonin at 10 mg/kg/day for 21 days). According to our study, brain oxidant/antioxidant status, inflammatory mediators, and apoptosis changes during acrylamide exposure were higher in pinealectomized rats than in non-pinealectomized rats. In addition, histopathological changes were more common in the brain tissue of pinealectomized rats after acrylamide administration. Exogenous melatonin treatment increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS). In addition, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in acrylamide-exposed brain tissues. In addition, exogenous melatonin intervention in acrylamide-exposed rats significantly restored the structure of neuronal tissues. In conclusion, this study suggested for the first time that exogenous melatonin treatment may reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological changes in the brain tissue of pinealectomized rats after acrylamide administration."
Acrylamide is a chemical substance with high solubility in water, soluble well in polar solvents, and very slightly soluble in non-polar solvents. It is not found freely in nature and is synthesized by chemical means. Acrylamide is a toxic chemical carcinogen formed due to the preparation of carbohydrate-rich foods at high temperatures or other thermal processes. Since acrylamide is a toxic chemical substance, it affects the reproductive system, but also has genotoxic, carcinogenic, and neurotoxic effects. Acrylamide's researches, especially in the field of neurotoxicity, have received great attention. It has been observed that acrylamide causes neuropathy in rats as well as in humans depending on the dose rate and concentration of the severity of neurological disorders and the progression of symptoms, and even fatal at increasing doses. The hormone melatonin, which is secreted from the pineal gland of mammals and regulates various circadian rhythms, plays an important role in physiological and metabolic events such as neuroprotective effect, anti-amyloid effect, antilipidemic, antihypertensive and antioxidant defense. In addition, as a result of the research carried out after the discovery of its free radical scavenging feature, its metabolites formed when it functions in the detoxification of radicals also have radical scavenging properties. In our study, melatonin deprivation was created by applying pinealectomy to rats. Subsequently, rats undergoing pinealectomy and Sham pinealectomy were exposed to acrylamide (25 mg/kg body weight, orally) alone or in the presence of exogenous melatonin (10 mg/kg body weight, i.p.) for 21 consecutive days. Thus, we aimed to evaluate the possible effects of exogenous melatonin combined with acrylamide on neurotoxicity and the possible role of acrylamide-induced neurotoxicity, considering the oxidative stress markers and serum melatonin levels in the brain/cerebellum tissue of Wistar albino rats, as well as the histopathological and immunohistochemical evaluations of the brain/cerebellum tissue. For this purpose, after sixty rats were divided into two main groups as Sham and pinealectomy, they were divided into three groups in each of these two main groups; (a) Sham (0.5% ethanol solution administered i.p. for 21 days), (b) Sham+AKR group (25 mg/kg/day acrylamide was given by gavage for 21 days during the experiment), (c) Sham+AKR+MLT (acrylamide 25 mg/kg/day was administered by gavage for 21 days, melatonin 10 mg/kg/day was administered as ip for 21 days in 0.5 ml volume during the experiment), (d) PINX group (After the pineal gland was removed by pinealactomy, 0.5% ethanol solution was applied i.p for 21 days during the experiment) (e) PINX + AKR group (after the pineal gland was removed by pinealactomy, i.p for 21 days during the experiment) 0.5% ethanol solution was gavaged at 25 mg/kg/day acrylamide for 21 days), (f) PINX+AKR+MLT (After pineal gland removal by pinealactomy, 0% i.p. for 21 days during the experiment. A 5% ethanol solution was administered by gavage at 25 mg/kg/day acrylamide for 21 days, and melatonin at 10 mg/kg/day for 21 days). According to our study, brain oxidant/antioxidant status, inflammatory mediators, and apoptosis changes during acrylamide exposure were higher in pinealectomized rats than in non-pinealectomized rats. In addition, histopathological changes were more common in the brain tissue of pinealectomized rats after acrylamide administration. Exogenous melatonin treatment increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) and improved brain total antioxidant status (TAS). In addition, melatonin suppressed lipid peroxidation, inflammatory pathways and apoptosis in acrylamide-exposed brain tissues. In addition, exogenous melatonin intervention in acrylamide-exposed rats significantly restored the structure of neuronal tissues. In conclusion, this study suggested for the first time that exogenous melatonin treatment may reduce oxidative damage by increasing the activities of antioxidant enzymes, inhibiting lipid peroxidation and inflammation, and improving histopathological changes in the brain tissue of pinealectomized rats after acrylamide administration."
Açıklama
Anahtar Kelimeler
Pinealektomi, Melatonin, Nörotoksisite, Lipid Peroksidasyon, İnflamasyon, Akrilamid, Oksidatif Stres, Pinealectomy, Melatonin, Neurotoxicity, Lipid Peroxidation, Inflammation, Acrylamide, Oxidative Stress.
