Maternal sciatic nerve administered bupivacaine induces hippocampal cell apoptosis in offspring
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RESEARCH ARTICLE
Open Access
Maternal sciatic nerve administered bupivacaine induces hippocampal cell apoptosis in offspring Alireza Mirkheshti1, Alireza Shakeri1, Elham Memary1, Mansoureh Baniasadi2, Jalal Zaringhalam2*, Ardeshir Tajbakhsh1, Marzieh Mirzaei3 and Elena Lak4
Abstract Background: Bupivacaine, an amid-type local anesthetic, is widely used for clinical patients especially in pregnant women. In addition to neurotoxicity effect of bupivacaine, it can cross the placenta, accumulates in this tissue and retained in fetal tissues. Nevertheless, whether bupivacaine can cause neurotoxicity in fetus remains unclear. Hence, this study was design to investigate the effects of maternal bupivacaine use on fetus hippocampal cell apoptosis and the possible related mechanism. Methods: On day 15 of pregnancy, sciatic nerve of pregnant wistar rat (180–200 g) were exposed by lateral incision of the right thigh and 0.2 ml of bupivacaine was injected. After their delivery, we randomly selected one male offspring of every mother. On day 30 after of their birth, the rat’s hippocampi were isolated for molecular studies. Western blotting was used to examine the expression of cleaved caspase-3, caspase-8 and p-Akt in fetal hippocampus. Results: Our results showed that maternal bupivacaine use caused a significant increment of cleaved caspase-3 and caspase-8 expression in fetal hippocampus compared with the sham group. In addition, maternally administered bupivacaine could significantly decrease hippocampal P.Akt/T.Akt ratio which was concurrent with an increment of cleaved caspase-3 and caspase-8 expression. Conclusion: Our data suggest that maternal bupivacaine use increases fetal hippocampal cell apoptosis markers such as caspase 8 and cleaved caspase 3, at least in part, via inhibiting the Akt activation. Keywords: Bupivacaine, Apoptosis, Akt, Pregnancy
Background Bupivacaine, an amid-type local anesthetic, is widely used for spinal and epidural anesthesia, peripheral nerve blockade, sympathetic nerve block and postoperative analgesia in clinical patients, especially in pregnant patients by providing excellent sensory anesthesia [1, 2]. However, local anesthetics may have potential neurotoxicity * Correspondence: [email protected] 2 Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Full list of author information is available at the end of the article
and induce nonreversible neurological complications [1, 3–5]. In this regard, a growing body of data indicates that bupivacaine triggers a complex cascade response leading to neuronal apoptosis [6–9]. It has been reported that disruption of calcium homeostasis, reduced mitochondrial membrane potential, ROS generation and DNA damage in the neuronal population are implicated in the pathogenesis of bupivacaine-induced neurotoxicity [3, 10, 11]. The exact mechanisms by which bupivacaine induces apoptosis have not been elucidated entirely. However, different studies have reported that several
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