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

Highlights

  • Mesenteric obstruction leads to intestinal ischemia, and it is associated with complications of surgical emergencies such as hypovolemic shock, sepsis and trauma [1]

  • GK potentiated the effect of KTM100 on ROS production in the intestinal tissue of rats with I/Rinduced injury

  • The results of the present study suggest that KTM100 and GK treatments significantly reduced the levels of cytokines in the intestinal tissues of rats with I/R-induced intestinal injury

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Summary

Introduction

Mesenteric obstruction leads to intestinal ischemia, and it is associated with complications of surgical emergencies such as hypovolemic shock, sepsis and trauma [1]. The intestine is very sensitive to alterations in blood supply. Intestinal tissue reperfusion enhances the production of cytokines and free radicals which alter gastrointestinal motility and damage the mucosal layer, thereby altering the integrity of. -©---2-0--2--1--T--h--e--a--u-t-h--o--r-s-.--T--h-i-s--w--o--r-k--i-s--l-i-c-e--n--s-e--d--u--n--d-e--r--t-h-e---C--r-e--a-t-i-v-e---C--o--m--m---oT-n-r-so--pA--tJ-t-r-Pi-b-hu-a-t-ir-om-n---R4-.-e0-s-,-I-nJ-t-ae-n-r-nu-a-a-tr-i-oy-n-2-a-0-l2-L-1-ic-;-e2--n0-s-(-e1--)-:--1-1 intestinal tissues [3]. Intestinal I/R enhances the protein expression levels of adhesion molecules such as ICAM-1 and selectin [4]. It has been reported that intestinal contractility is altered by intestinal I/R due to damage to the neurons of myenteric plexus [5]. Intestinal ischemia results in necrosis of intestinal tissues which is managed through surgical excision [6]. Very few treatment therapies are available for managing intestinal ischemia

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