Relationship between SIRT1-ERK1/2 pathway and chikusetsu saponin IVa-induced reduction of isoflurane-elicited neurotoxicity in fetal rats: an in vitro experiment

Abstract

Objective To evaluate the relationship between silent information regulator 1 (SIRT1)-extracellular-regulated kinase1/2 (ERK1/2) pathway and chikusetsu saponin IVa-induced reduction of isoflurane-elicited neurotoxicity in fetal rats in an in vitro experiment. Methods The hippocampal neurons isolated from rats at 16-18 days of gestation were primarily cultured for 7 days and divided into 3 groups (n = 6 each) using a random number table method: control group (Con group), isoflurane group (Iso group) and chikusetsu saponin IVa plus isoflurane group (ChIV+ Iso group). Hippocampal neurons were cultured routinely for 6 h in Con group.Hippocampal neurons were exposed to 1.8% isoflurane for 6 h in an incubator in Iso group.Chikusetsu saponin IVa 25 μg/ml was added to the culture medium, and hippocampal neurons were incubated for 6 h and then exposed to 1.8% isoflurane for 6 h in an incubator in ChIV+ Iso group.The supernatant was collected for determination of the amount of lactic dehydrogenase (LDH) released, neuronal viability (by CCK-8) and expression of SIRT1, ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) (by Western blot). Results Compared with Con group, the neuronal viability was significantly decreased, the amount of LDH released was increased, and the expression of SIRT1 and p-ERK1/2 was down-regulated in Iso group (P<0.05). Compared with Iso group, the neuronal viability was significantly increased, the amount of LDH released was decreased, and the expression of SIRT1 and p-ERK1/2 was up-regulated in ChIV+ Iso group (P<0.05). Conclusion The mechanism by which chikusetsu saponin IVa reduces isoflurane-elicited neurotoxicity is related to activating SIRT1-ERK1/2 pathway in fetal rats in an in vitro experiment. Key words: Isoflurane; Sirtuins; Extracellular signal-regulated MAP kinases; Drug toxicity; Neurons