Author/Editor		Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmić, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikirić, Predrag
Title		Effects of diclofenac, L-NAME, L-arginine, and pentadecapeptide BPC 157 on gastrointestinal, liver, and brain lesions, failed anastomosis, and intestinal adaptation deterioration in 24 hour-short-bowel rats
Type		članek
Vol. and No.		Letnik 11, št. 9
Publication year		2016
Volume		str. 1-18
ISSN		1932-6203 - PloS one
Language		eng
Abstract		Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound heal-ing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anasto-mosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac(12 mg/kg), BPC 157 (10[micro]g/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowelrats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated byimmediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAMEinduced further aggravation and lesions gradually worsened. Specifically, rats with surgeryalone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed wide spread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cere-brum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the men-tioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, ratssubjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjectedto surgery and administered diclofenac showed worse symptoms, than the rats subjected tosurgery alone did. Rats subjected to surgery combined with diclofenac and L-NAMEshowed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation ofthe remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and L-NAME. BPC 157 completely amelio-rated symptoms in massive intestinal resection-, massive intestinal resection plus diclofe-nac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowelrats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine amelio-rated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.
Keywords		L-Arginine effects of diclofenac anastomosis L-arginina učinki diklofenaka anastomoza