Role of dantrolen and ketamine in the apoptotic effect of isoflurane in rats

Thirty Wistar male rats were randomly assigned to five groups, each containing n=6, in order to investigate the effects of ketamine and/or dantrolen on the isoflurane induced apoptosis. Oxygen 100% was administered into the closed cage for 2 hours in the control group, whereas 1.4% isoflurane in 100% oxygen was administered in the other 4 groups. Six hours after intraperitoneal injection of dantrolen 10 mg/kg (Group Iso+Dant), ketamine 40 mg/kg (Group Iso+Ket) and dantrolen + ketamine (Group Iso+Dant+Ket), rats were sacrified. Immunoreactive cells in the hypocampus CA-1 region for caspase 3 in group Iso+Ket and for caspase 8 and 9 in group Iso, group Iso+Ket, and group Iso+Ket+Dant were significantly higher than the control group. However, no significant differences were observed for caspase 3, 8 and 9 in the group Iso+Dant. Immunoreactive cells in the hypocampus CA-1 region for caspase 3, 8 and 9 in group Iso+Ket were significantly higher than all groups, whereas it was higher in group Iso with respect to only group Iso+Dant and it was higher for group Iso+Ket+Dant than group Iso+Dant. Significantly more immunoreactive cells in the dentat gyrus region for caspase 3 and 8 in groups Iso and Iso+Ket and for caspase 9 in groups Iso, Iso+Ket, and Iso+Ket+Dant versus control were observed. However, no significant differences were found for caspase 3, 8 and 9 in group Iso+Dant. Caspase 3 and 8 in group Iso+Ket was significantly more than the other groups. Whereas caspase 9 results in group Iso+Ket was similar to group Iso but higher than that of groups Iso+Dant and Iso+Ket+Dant. Caspase 3 and 9 results in group Iso+Ket+Dant was significantly lower than only group Iso. Csapase 3, 8 and 9 results were similar between groups Iso+Ket+Dant and Iso+Dant. As a result, isoflurane induced apoptosis increased by ketamine and decreased by dantrolen.