Effects of thymoquinone on valproic acid-induced oxidative stress in perinatal rat brain

Öz

Thymoquinone (TQ), bioactive molecule of black cumin, has antioxidant and neuroprotective effects. TQ’s hypoglecemic effect while applied prenatally is reported. This study is aimed to find the TQ dose with maximum antioxidant and minimum side effects in valproic acid (VPA) induced oxidative stress. Pregnant Wistar rats were injected i.p. with 400 mg/kg/ml of VPA on embryonic day 12.5 (E12.5). Repeated dose groups were injected i.p. from E11.5- E14.5; RC- repeated control: did not receive TQ, R1: 0.5 mg/kg/ml of TQ, R2: 2 mg/kg/ml of TQ, R3: 4 mg/kg/ml of TQ, R4: 8 mg/kg/ml of TQ. Single dose groups were injected i.p. on E12.5; SC- single control: did not receive TQ, S1: 8 mg/kg/ml of TQ, S2: 15 mg/kg/ml of TQ. Pups were sacrificed on postnatal day 7. Glutathione (GSH), malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured via ELISA method. Prenatal VPA exposure decreased GSH and SOD levels in RC and SC compared to naïve group. R3 group showed improved GSH and SOD levels compared to RC. No significant difference in MDA levels was found between groups. Antioxidant effects of TQ on VPA induced oxidative stress has been showed in R3 group. This dose can be used to investigate TQ’s effects on other parameters that are affected by prenatal VPA exposure.

Anahtar Kelimeler

• Oxidative Stress
• Thymoquinone
• Valproic Acid
• Perinatal Brain
• Rat

Timokinonun perinatal sıçan beyninde valproik asit indüklü oksidatif stres üzerine etkileri

Öz

Timokinon (TQ), çörek otunun aktif maddesi, antioksidan ve nöroprotektif etkileri olan bir maddedir. Prenatal dönemde uygulandığında hipoglisemi etkisi bildirilmiştir. Bu çalışmanın amacı TK’nun perinatal sıçan beyninde Valproik Asit (VPA) indüklenmiş oksidatif streste kullanımı için maksimum antioksidan ve minimum yan etkiye sahip dozunun bulunmasıdır. Gebe Wistar sıçanlara 12,5. embriyonik günde (E12.5), i.p. 400mg/kg VPA enjeksiyonu uygulanmıştır. Tekrarlayan TK doz gruplarına (R) E11,5-E14,5 arası, Tek doz TK gruplarına (S) ise E12,5’de i.p. TK uygulanmıştır. RC: tekrarlayan kontrol, TQ yok; R1: 0.5 mg/kg/ml TK; R2: 2 mg/kg/ml TQ, R3: 4 mg/kg/ml TQ, R4: 8 mg/kg/ml TQ; SC- tek doz kontrol, TQ yok; S1: 8 mg/kg/ml TQ, S2: 15 mg/kg/ml TQ. Yavrular postnatal 7. günde sakrifiye edilerek total beyin dokularında ELISA yöntemiyle glutatyon (GSH), malondealdehit (MDA) ve süperoksit dismütaz (SOD) seviyeleri ölçülmüştür. Prenatal VPA uygulaması RC ve SC gruplarında naive gruba göre GSH ve SOD miktarlarını azaltmıştır. R3 grubunda kontrol grubuna göre artmış GSH ve SOD seviyeleri ölçülmüştür. Hiçbir grupta MDA seviyelerinde farklılık görülmemiştir. TK’nun VPA indüklü oksidatif stres üzerinde yan etki olmaksızın antioksidan etkisi R3 grubunda gösterilmiştir. Bu doz prenatal VPA asit maruziyetinin olumsuz olarak değiştirdiği davranış ve beyin morfolojisi gibi diğer parametrelerin incelenmesinde kullanılmak üzere önerilmektedir.

Anahtar Kelimeler

• Oksidatif Stres
• Timokinon
• Valproik Asit
• Perinatal Beyin
• Sıçan

Kaynakça

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