Mangan ile indüklenen hücre toksisitesinde mitokondriyal hasarın ve oksidatif stresin rolünün araştırılması
Küçük Resim Yok
Tarih
2015
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Mangan (Mn) organizma için esansiyel bir element olup vücutta birçok önemli fizyolojik süreçte görev yapar. Ancak çevresel ve mesleksel kaynaklı aşırı Mn maruziyeti özellikle sinir sisteminde hareket ve kognitif işlevlerde bozukluğa neden olabilir. Mn'ın bu etkilerinin ortaya çıkmasında oksidatif stresin rolünün olduğu bildirilmekle birlikte altta yatan mekanizma henüz tam olarak aydınlatılamamıştır. Bu çalışmadaki amacımız Mn'ın kronik maruziyetinin beyindeki etkilerinin mitokondriyal oksidatif stresle bağlantılı olup olmadığını araştırmaktı. Ayrıca özellikle nörodejeneratif süreçlerdeki antioksidan etkileri bilinen edaravonun (EDA) Mn maruziyetine bağlı gelişen nörotoksisiteye karşı koruyucu etkisi de araştırıldı. Bu amaçla 40 adet erişkin erkek Sprague Dawley sıçan Grup 1: Serum fizyolojik, Grup 2: Mn (10 mg/kg) + serum fizyolojik, Grup 3: Mn + EDA 1mg/kg ve Grup 4: Mn + EDA 5 mg/kg olarak gruplara ayrıldı. Mn ve ilaç uygulamaları 28 gün boyunca intraperitoneal (Mn) ve intramuskuler (EDA) yolla gerçekleştirildi. Bu sürenin sonunda sıçanların kaba motor güçleri ve Mn'ın beyindeki dağılımı MR görüntüleme yöntemi ile tayin edildi. Sonrasında beyin dokuları çıkarıldı ve mitokondri izolasyonu yapıldı. Mitokondriyal örneklerde elektron transport zinciri enzimi kompleks I aktivitesi, lipid peroksid ve protein karbonil düzeyi ölçüldü. Çalışma bulguları tek yönlü varyans analizi (ANOVA) ve post hoc Bonferonni testleri ile değerlendirildi. İstatistiksel değerlendirmeler Mn'ın beyinde kompleks I aktivitesini anlamlı derecede inhibe ettiğini (p<0.0005), lipid peroksid ve protein karbonil düzeylerini de anlamlı dereced yükselttiğini (p<0.0005) ortaya koydu. EDA'nın Mn ile birlikte uygulanmasının bu etkileri doza bağlı azalttığı gözlendi. Sonuç olarak çalışmamız sıçanda kronik Mn maruziyetinin beyinde yarattığı toksisitenin mitokondriyal oksidatif strese bağlı olarak geliştiğini gösterdi. Çalışmamızın bir diğer sonucu ise, bir antioksidan olan edaravonun Mn maruziyetine bağlı gelişen toksisitenin önlenmesinde etkili bir ajan olabileceğinin gösterilmesi oldu
Manganese (Mn), an essential dietary element, has important roles in several physiological processes in the body. However, accumulation of Mn due to excessive environmental and occupational exposure leads to movement abnormalities and cognitive impairment. Although oxidative stress has been hypothesized to play a role in this dysfunction, the underlying mechanisms still need to be elucidated. In the present study, we aim to investigate the effects of chronic Mn toxicity in brain and its relation with mitochondrial oxidative stress. Also, we examined whether edaravone (EDA), a radical scavenger, exerts cytoprotective effects against Mn neurotoxicity. Forty adult male Sprague Dawley rats were included in the study. Study groups were designed as follows: Group 1: Saline, Group 2: Mn (10 mg/kg), Group 3: Mn + EDA 1mg/kg and Group 4: Mn + EDA 5 mg/kg. All treatments were performed intraperitoneally (Mn) and intramuscularly (EDA) through 28 days. At the end of the treatment period, gross motor performance was measured and distribution of Mn in brain regions was detected using MR imaging. Then, brain tissues were dissected and and electron transport chain enzyme complex I activity, lipid peroxide and protein carbonyl levels were determined in mitochondrial fractions. All data were analyzed by one way ANOVA and post-hoc Bonferonni test. According to our findings, complex I activity was significantly decreased in Mn + saline group compared to saline group (p<0.0005) whereas lipid peroxide and protein carbonyl levels were significantly increased (p<0.0005). Administration of edaravone significantly and dose-dependently prevented cytotoxicity against Mn exposure. Overall, our results reveal that chronic Mn exposure may lead to cytotoxicity in rat brain through mitochondrial oxidative stress. Moreover, edaravone, as an antioxidant agent, may have cytoprotective effects against Mn exposure.
Manganese (Mn), an essential dietary element, has important roles in several physiological processes in the body. However, accumulation of Mn due to excessive environmental and occupational exposure leads to movement abnormalities and cognitive impairment. Although oxidative stress has been hypothesized to play a role in this dysfunction, the underlying mechanisms still need to be elucidated. In the present study, we aim to investigate the effects of chronic Mn toxicity in brain and its relation with mitochondrial oxidative stress. Also, we examined whether edaravone (EDA), a radical scavenger, exerts cytoprotective effects against Mn neurotoxicity. Forty adult male Sprague Dawley rats were included in the study. Study groups were designed as follows: Group 1: Saline, Group 2: Mn (10 mg/kg), Group 3: Mn + EDA 1mg/kg and Group 4: Mn + EDA 5 mg/kg. All treatments were performed intraperitoneally (Mn) and intramuscularly (EDA) through 28 days. At the end of the treatment period, gross motor performance was measured and distribution of Mn in brain regions was detected using MR imaging. Then, brain tissues were dissected and and electron transport chain enzyme complex I activity, lipid peroxide and protein carbonyl levels were determined in mitochondrial fractions. All data were analyzed by one way ANOVA and post-hoc Bonferonni test. According to our findings, complex I activity was significantly decreased in Mn + saline group compared to saline group (p<0.0005) whereas lipid peroxide and protein carbonyl levels were significantly increased (p<0.0005). Administration of edaravone significantly and dose-dependently prevented cytotoxicity against Mn exposure. Overall, our results reveal that chronic Mn exposure may lead to cytotoxicity in rat brain through mitochondrial oxidative stress. Moreover, edaravone, as an antioxidant agent, may have cytoprotective effects against Mn exposure.
Açıklama
Anahtar Kelimeler
Fizyoloji, Physiology
