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.
Lojo. Nermin N; Rasic. Zarko Z; Zenko Sever. Anita A; Kolenc. Danijela D; Vukusic. Darko D; Drmic. Domagoj D; Zoricic. Ivan I; Sever. Marko M; Seiwerth. Sven S; Sikiric. Predrag P
Key Findings
- BPC‑157 completely prevented worsening of gut, liver and brain lesions in rats after massive small‑bowel resection, even when they were also given diclofenac or the NOS blocker L‑NAME.
- Diclofenac alone, and especially combined with L‑NAME, dramatically increased tissue damage and impaired intestinal adaptation.
- L‑arginine only improved outcomes when the nitric‑oxide pathway was blocked (L‑NAME), but did not add benefit beyond BPC‑157 alone.
Practical Outcomes
- For biohackers, BPC‑157 looks promising as a protective agent for gut healing and to counteract NSAID‑related damage, especially after major abdominal surgery or severe intestinal stress. A dose around 10 µg/kg (roughly 0.7 mg for a 70 kg human) given intraperitoneally was effective in rats, but human dosing and safety are not established. Pairing BPC‑157 with L‑arginine might help if nitric‑oxide pathways are compromised, but the main takeaway is that BPC‑157 alone showed strong protective effects in this animal model.
Summary
In rats that had most of their small intestine removed, the peptide BPC‑157 (given right after surgery) stopped the severe gut, liver and brain damage that normally gets worse when NSA‑painkillers like diclofenac are taken. Adding L‑arginine helped a bit when the nitric‑oxide system was blocked, but BPC‑157 alone was enough to protect the animals.
Abstract
Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing 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 anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the 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 ameliorated symptoms in massive intestinal resection-, massive intestinal resection plus diclofenac-, and massive intestinal resection plus diclofenac plus L-NAME-treated short bowel rats that presented with cyclooxygenase (COX)-NO-system inhibition. L-arginine ameliorated only L-NAME-induced aggravation of symptoms in rats subjected to massive intestinal resection and administered diclofenac plus L-NAME.
Study Information
pubmed
2016
2016-09-14T00:00:00.000Z
10.1371/journal.pone.0162590
51
41