Ginkgolide K potentiates the protective effect of ketamine against intestinal ischemia/reperfusion injury by modulating NF-κB/ERK/JNK signaling pathway

Abstract

Purpose: To investigate the effect of ginkgolide K and ketamine treatments, alone and in combination, on intestinal  ischemia/reperfusion injury (I/R)-induced injury in rats, as well as the mechanism involved. Methods: Rats were treated with ginkgolide K (GK, 15 mg/kg i.v) and ketamine (KTM, 100 mg/kg i.p.), either alone or in combination 30 min before the induction of intestinal I/R. The effects of GK and KTM were determined by assessing the levels of cytokines in serum, and parameters of oxidative stress and ROS production in the intestinal tissues of I/R rats. Moreover, intestinal mRNA expressions of JNK, ERK, p38 and NF-kB were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: GK and KTM treatments, alone and in combination, reduced cytokine levels in serum and oxidative stress parameters in intestinal tissues, when compared to I/R group of rats. Treatments with GK and KTM, alone and in combination, mitigated the altered mRNA expressions of JNK, ERK, p38 and NF-kB in intestinal tissues of I/R-injured rats. Conclusion: These results reveal that GK potentiates the protective effect of KTM100 on I/R-induced intestinal injury in rats by regulating the NF-kB/ERK/JNK signaling pathway. Therefore, GK and KTM may find use in the management of I/R Keywords: Ginkgolide K, Ketamine, Intestinal injury, Ischemia/Reperfusion, Inflammation