Sıçan hipokampüsünde izofluran, ketamin ve dantrolenin apoptozis üzerine etkileri

Abstract

Amaç: Hem izofluran ve ketaminin nörodejeneratif apoptotik etkileri gösterilmiş hem de dantrolenin dejenerasyonu inhibe ettiği bilindiği için biz isoflurane ve/veya ketamine anestezisi altında dantrolenin sitoprotekif bir rolü olup olamayacağını araştırdık. Bu nedenle sıçan hipokampüsünde (CA1 ve dentat girus bölgelerinde) apoptozisin belirteci olan kaspaz aktivasyonunu; izofluranı ketamine ve dantrolen varken veya yokken veya izofluran+ketamin+dantrolen varlığında belirlemeyi amaçladık Gereç ve Yöntemler: Wistar 30 erkek sıçan rastgele beş gruba ayrıldı. Kontrol grubunda 2 saat sadece %100 oksijen verilirken, dört çalışma grubunda (A.B,C ve D) ya sadece %100 oksijen içinde %1.4 izofluran (grup B) veya intraperitoneal (ip) dantrolen 10 mg/kg enjeksiyonundan (grup C), subkutan (sk) ketamin 40 mg/kg enjeksiyonundan (group D) ya da ip dantrolen + sk ketamine enjeksiyonundan (group E) 60 dk sonra %100 oksijen içinde %1.4 izofluran uygulanmıştır. Sonra sıçanlar histopatolojik ve immunohistokimyasal inceleme (hematoxylin boyama ile kaspas aktivasyonu) için sakrifiye edilmişlerdir. Bulgular: Sadece izofluran (grup B) ve izofluran+ketamine (grup D) maruz kalan sıçanlarda kontrol grubuna (grup A) göre hipokampüsde kaspas aktivasyonunda önemli artış ile dantrolenin izofluran+ketaminle indüklenmiş apoptozisi inhibe ettiği gözlendi. Sonuç: İzofluranın ketamine varken ya da yokken sıçanda nöroapoptozise neden olduğu ve dantrolenle; izofluran ve izofluran+ketaminin apoptotik etkisinin azalan kaspaz aktivasyonuyla olduğu gösterilmiştir. Bu sonuçlar ileri klinik çalışmalardan sonra duyarlı grupların anestezi seçimde rol oynabilir.

Keywords

• Izofluran
• ketamin
• dantrolen
• apoptozis

Project Number

110S514

Effects of isoflurane, ketamine and dantrolene on apoptosis in the rat hippocampus

Abstract

Aim: Since both isoflurane and ketamine were already known to cause neurodegenerative apoptotic effects and dantrolene was known to inhibit degeneration, we investigated whether dantrolene could play a cytoprotective role under isoflurane and/or ketamine anesthesia. Therefore, we aimed to determine caspase activation as a marker of apoptosis in hippocampus (CA1 and dentate gyrus regions) of rats exposed to either administration of isoflurane with or without ketamine and dantrolene or isoflurane+ketamine+dantrolene. Material and Methods: Thirty Wistar male rats were randomly assigned to five groups. Only oxygen 100% was administered into the closed cage for 2 hours in the control group (group A) whereas in the four study groups (as B,C,D and E), either 1.4% isoflurane alone in 100% oxygen was administered (group B) or 1.4% isoflurane in 100% oxygen was administered 60 minutes after intraperitoneal (ip) injection of dantrolene 10 mg/kg (group C), subcutaneous (sc) ketamine 40 mg/kg (group D) or ip dantrolene + sc ketamine (group E). Rats were sacrified to perform histopathologic and immunohistochemical analysis (hematoxylin staining caspase activation). Results: Isoflurane alone (group B) and isoflurane+ketamine (group D) exposure to rats resulted in a significantly increased caspase activation when compared to control (group A) and dantrolene inhibited isoflurane + ketamine induced apoptosis in the hippocampus. Conclusion: Isoflurane with or without ketamine caused neuroapoptosis in rats and dantrolene attenuated the apoptotic effect of both isoflurane and isoflurane+ketamine by decreasing caspase activation. These results might have an important promising role in anesthetic choice for specific susceptible group after further clinical studies.

Keywords

• Isoflurane
• ketamine
• dantrolene
• apoptosis

Supporting Institution

TUBİTAK

Project Number

110S514

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