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.

Key words: Isoflurane; ketamine; dantrolene; apoptosis