The herbal medicine, Dai-Kenchu-to, accelerates delayed gastrointestinal transit after the operation in rats.
BACKGROUND
Post-operative ileus (POI) is a transient bowel dysmotility after operation. We have previously shown that laparotomy alone significantly delayed gastrointestinal (GI) transit, compared to anesthesia alone. The GI transit was further delayed after laparotomy plus intestinal manipulation. Dai-Kenchu-to (DKT), an herbal medicine, has been used for treating adhesive bowel obstruction in Japan. We studied whether DKT improves delayed GI transit after the operation, with or without morphine administration in rats.


METHODS
Under isoflurane anesthesia, POI was induced by laparotomy with intestinal manipulation. Immediately after the operation, the rats received 51Cr by gavage. Three hours after the operation, the rats were sacrificed and GI transit was estimated by calculating the geometric center (GC). DKT (120, 360, and 1,200 mg/kg) were administered by gavage after the operation, with or without morphine administration (1 mg/kg s.c.). A muscarinic receptor antagonist (atropine; 50 mug/kg), a 5HT3 receptor antagonist (ondansetron; 1 mg/kg) and a 5HT4 receptor antagonist (GR113,808; 3 mg/kg) were administered before the operation. Truncal vagotomy was performed preceding the operation.


RESULTS
Laparotomy with intestinal manipulation produced a significant delay in GI transit (GC = 2.93 +/- 0.16), compared to that of anesthesia alone (9.51 +/- 0.45). DKT at the dose of 360 mg/kg (GC = 3.77 +/- 0.10, P < 0.01) and 1,200 mg/kg (GC = 3.77 +/- 0.20, P < 0.01) significantly accelerated delayed GI transit induced by operation. Ondansetron, GR113,808, atropine, and truncal vagotomy abolished the stimulatory effect of DKT (360 mg/kg). When morphine was administered, GI transit was further reduced (GC = 1.97 +/- 0.10). DKT at the dose of 360 mg/kg (GC = 2.81 +/- 0.22, P < 0.05) and 1,200 mg/kg (GC = 2.87 +/- 0.23, P < 0.05) significantly improved delayed GI transit in morphine treated rats.


CONCLUSIONS
DKT accelerates delayed GI transit induced by intestinal manipulation with and without concomitant morphine administration. DKT treatment may be useful for the patients with POI.
Fukuda
Hiroyuki
H
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27705, USA.
Chen
Cindy
C
Mantyh
Christopher
C
Ludwig
Kirk
K
Pappas
Theodore N
TN
Takahashi
Toku
T
D000701:Analgesics, Opioid / Q000009:adverse effects; D000818:Animals; D005772:Gastrointestinal Transit / Q000187:drug effects*; D045823:Ileus / Q000188:drug therapy* / Q000209:etiology; D007813:Laparotomy / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000009:adverse effects; D005894:Panax; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D032106:Zanthoxylum; D030521:Zingiberaceae
D000701:Analgesics, Opioid; D010936:Plant Extracts; C121414:dai-kenchu-to; D009020:Morphine