.: ORİJİNAL ARAŞTIRMA
The Effects of Levetiracetam as Anti-Epileptic Drug on Bone and Vitamin D Metabolism
Anti-Epileptik İlaç Olarak Levetirasetam'ın Kemik ve D Vitamini Metabolizması Üzerine Etkileri
Turkiye Klinikleri J Med Sci. 2020;40(3):349-57
doi: 10.5336/medsci.2020-73684
Makale Dili: EN
Tam Metin
ABSTRACT
Objective: Levetiracetam (LEV) is one of the new generations of anti-epileptic drugs. There are controversial results reported in the literature for the effects of LEV on bone metabolism. Some studies reported low bone mineral density (BMD) and vitamin D values with high bone turnover markers, while the others reported no effect on BMD. This study is the first report on elucidation of the mechanism of LEV and seizures on vitamin D and bone metabolism. Material and Methods: 100 mg/kg of LEV in each day was given to rats for twelve weeks. 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium, bone turnover markers and parathyroid hormone (PTH) were measured by Enzyme-Linked Immunosorbent Assay (ELISA) while the protein levels of anabolic and catabolic enzymes of vitamin D were measured by western blot. Results: The serum levels of calcium, 25(OH)D and 1,25(OH)2D were significantly reduced in all rats, while there were increased amounts of PTH in just LEV-treated rats compared to the control. High bone turnover markers were also observed for drug-treated groups. Both epileptic seizures and LEV increased the amount of 24-hydroxylase; vitamin D catabolic enzyme. Conclusion: Based on the findings of the current study, both the LEV treatment and seizures cause vitamin D deficiency in rats by increasing the 24-hydroxylase amount in epileptic and LEV-treated groups which resulted in the conversion of active vitamin D to an inactive form and reduction in 25(OH)D and 1,25(OH)2D amounts.
Keywords: Bone; levetiracetam; vitamin D; bone turnover markers; parathyroid hormone (PTH); epilepsy; genetically-induced absence seizures; WAG/Rij rats; calcium; 25(OH)D
Objective: Levetiracetam (LEV) is one of the new generations of anti-epileptic drugs. There are controversial results reported in the literature for the effects of LEV on bone metabolism. Some studies reported low bone mineral density (BMD) and vitamin D values with high bone turnover markers, while the others reported no effect on BMD. This study is the first report on elucidation of the mechanism of LEV and seizures on vitamin D and bone metabolism. Material and Methods: 100 mg/kg of LEV in each day was given to rats for twelve weeks. 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], calcium, bone turnover markers and parathyroid hormone (PTH) were measured by Enzyme-Linked Immunosorbent Assay (ELISA) while the protein levels of anabolic and catabolic enzymes of vitamin D were measured by western blot. Results: The serum levels of calcium, 25(OH)D and 1,25(OH)2D were significantly reduced in all rats, while there were increased amounts of PTH in just LEV-treated rats compared to the control. High bone turnover markers were also observed for drug-treated groups. Both epileptic seizures and LEV increased the amount of 24-hydroxylase; vitamin D catabolic enzyme. Conclusion: Based on the findings of the current study, both the LEV treatment and seizures cause vitamin D deficiency in rats by increasing the 24-hydroxylase amount in epileptic and LEV-treated groups which resulted in the conversion of active vitamin D to an inactive form and reduction in 25(OH)D and 1,25(OH)2D amounts.
Keywords: Bone; levetiracetam; vitamin D; bone turnover markers; parathyroid hormone (PTH); epilepsy; genetically-induced absence seizures; WAG/Rij rats; calcium; 25(OH)D
ÖZET
Amaç: Levetirasetam (LEV) yeni nesil anti-epileptik ilaçlardan biridir. Literatürde LEV'nin kemik metabolizması üzerindeki etkileri için tartışmalı sonuçlar vardır. Bazı çalışmalar, yüksek kemik döngüsü belirteçleri değeri ile düşük kemik mineral yoğunluğu (BMD) ve D vitamini değerleri bildirirken, diğerleri BMD üzerinde herhangi bir etki bildirmemiştir. Bu çalışma, LEV ve nöbetlerin D vitamini ve kemik metabolizması üzerindeki etki mekanizmasının aydınlatılması üzerine ilk rapordur. Gereç ve Yöntemler: On iki hafta boyunca sıçanlara her gün 100 mg/kg LEV verildi.25-hidroksivitamin D [25(OH)D] ve 1,25-dihidroksivitamin D [1,25(OH)2D], kalsiyum, kemik döngüsü belirteçleri ve paratiroid hormonu (PTH) Enzim bağlantılı immunosorbent testi (ELISA) ile, D vitamini anabolik ve katabolik enzimlerinin protein seviyeleri Western Blot tekniği ile ölçüldü. Bulgular: Serum kalsiyum, 25(OH)D ve 1,25(OH)2D seviyeleri tüm sıçanlarda önemli ölçüde azalırken, sadece LEV ile tedavi edilen sıçanlarda kontrole kıyasla artan miktarlarda PTH değeri vardı. İlaçla tedavi edilen gruplar için yüksek kemik döngüsü belirteçleri de gözlenmiştir. Hem epileptik nöbetler hem de LEV, D vitamini katabolik enzimi olan 24-hidroksilazın miktarını arttırdı. Sonuç: Mevcut çalışmanın bulgularına dayanarak, hem LEV tedavisi hem de nöbetler, epileptik ve LEV ile tedavi edilen gruplarda 24-hidroksilaz miktarını artırarak ve buna bağlı olarak aktif D vitamininin aktif olmayan bir forma dönüştürülmesine ve 25(OH)D ve 1,25(OH)2D miktarlarında azalmayı sağlayarak sıçanlarda D vitamini eksikliğine neden olmaktadır.
Anahtar Kelimeler: Kemik; levetiracetam; vitamin D; kemik döngüsü belirteçleri; paratiroid hormone (PTH); epilepsi; genetik olarak indüklenen absans nöbetleri; WAG/Rij sıçanlar; kalsiyum; 25(OH)D
Amaç: Levetirasetam (LEV) yeni nesil anti-epileptik ilaçlardan biridir. Literatürde LEV'nin kemik metabolizması üzerindeki etkileri için tartışmalı sonuçlar vardır. Bazı çalışmalar, yüksek kemik döngüsü belirteçleri değeri ile düşük kemik mineral yoğunluğu (BMD) ve D vitamini değerleri bildirirken, diğerleri BMD üzerinde herhangi bir etki bildirmemiştir. Bu çalışma, LEV ve nöbetlerin D vitamini ve kemik metabolizması üzerindeki etki mekanizmasının aydınlatılması üzerine ilk rapordur. Gereç ve Yöntemler: On iki hafta boyunca sıçanlara her gün 100 mg/kg LEV verildi.25-hidroksivitamin D [25(OH)D] ve 1,25-dihidroksivitamin D [1,25(OH)2D], kalsiyum, kemik döngüsü belirteçleri ve paratiroid hormonu (PTH) Enzim bağlantılı immunosorbent testi (ELISA) ile, D vitamini anabolik ve katabolik enzimlerinin protein seviyeleri Western Blot tekniği ile ölçüldü. Bulgular: Serum kalsiyum, 25(OH)D ve 1,25(OH)2D seviyeleri tüm sıçanlarda önemli ölçüde azalırken, sadece LEV ile tedavi edilen sıçanlarda kontrole kıyasla artan miktarlarda PTH değeri vardı. İlaçla tedavi edilen gruplar için yüksek kemik döngüsü belirteçleri de gözlenmiştir. Hem epileptik nöbetler hem de LEV, D vitamini katabolik enzimi olan 24-hidroksilazın miktarını arttırdı. Sonuç: Mevcut çalışmanın bulgularına dayanarak, hem LEV tedavisi hem de nöbetler, epileptik ve LEV ile tedavi edilen gruplarda 24-hidroksilaz miktarını artırarak ve buna bağlı olarak aktif D vitamininin aktif olmayan bir forma dönüştürülmesine ve 25(OH)D ve 1,25(OH)2D miktarlarında azalmayı sağlayarak sıçanlarda D vitamini eksikliğine neden olmaktadır.
Anahtar Kelimeler: Kemik; levetiracetam; vitamin D; kemik döngüsü belirteçleri; paratiroid hormone (PTH); epilepsi; genetik olarak indüklenen absans nöbetleri; WAG/Rij sıçanlar; kalsiyum; 25(OH)D
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