Clopidogrel-Induced Gastric Injury in Rats is Attenuated by Stable Gastric Pentadecapeptide BPC 157.
Wu. Hailu H; Wei. Ming M; Li. Nan N; Lu. Qin Q; Shrestha. Sachin Mulmi SM; Tan. Jiacheng J; Zhang. Zhenyu Z; Wu. Guoqiu G; Shi. Ruihua R
Key Findings
- Clopidogrel caused ulcer recurrence, inflammation, ER‑stress‑related cell death, and lowered angiogenic factors in rat stomachs.
- BPC‑157 markedly reduced ulcer recurrence, lowered apoptosis, restored VEGF‑A/VEGFR1 signaling, and activated AKT and p38/MAPK pathways.
- Blocking nitric‑oxide with L‑NAME weakened BPC‑157’s protective effects, indicating NO involvement.
Practical Outcomes
- For biohackers taking clopidogrel or other ulcer‑risk drugs, BPC‑157 may serve as a gut‑protective supplement. The data suggest it works by dampening stress‑related cell death and boosting healing signals, but human studies are still needed. If you choose to try it, start with low microgram doses, monitor stomach comfort, and consider that its benefits may rely on intact nitric‑oxide pathways.
Summary
In rats, the peptide BPC‑157 helped heal stomach ulcers that came back after taking the blood‑thinner drug clopidogrel. It reduced cell death and inflammation in the stomach lining and boosted blood‑vessel growth signals, but blocking nitric‑oxide made it less effective. This shows BPC‑157 can protect the gut from drug‑induced damage, at least in animal tests.
Abstract
Although Clopidogrel is safe in healthy volunteers, it can induce recurrence of gastric ulcers in high-risk patients. Here, we investigated the protective effect of the natural product, stable gastric pentadecapeptide 157 (BPC 157) on Clopidogrel-induced gastric injury. We used acetic acid to induce gastric ulcer in Sprague Dawley rats. Clopidogrel alone or in combination with BPC 157 or L-NAME (nitric oxide system blockade) were administered after healing of acetic acid-induced ulcer. One percent methylcellulose solution was used as control. Ulcer recurrence rate and the ulcer index were compared between these groups. Gastric mucosal apoptosis rate, microscopic inflammation activity and angiogenesis markers vascular endothelial growth factor A (<i>VEGF-A</i>) and <i>CD34</i> were examined by TUNEL, histological evaluations (HE) and immunohistochemistry (IHC). Pathways involved, expressions of endoplasmic reticulum (ER) stress apoptosis marker <i>CHOP</i>, angiogenic markers <i>VEGF-A</i> and its receptor <i>VEGFR1</i>, and endothelial NO synthase (<i>eNOS</i>) were all analyzed by Western blot. This study indicated that Clopidogrel significantly induced the gastric ulcers recurrence, severe inflammation and ER stress related apoptosis of the gastric mucosa, suppressed the synthesis of angiogenic markers and <i>eNOS</i>. Furthermore, Clopidrogel intervention resulted in the activation of protein kinase B (<i>AKT</i>) and p38 mitogen-activated protein kinase (<i>p38/MAPK</i>). BPC 157 attenuated the gastric mucosal damage caused by Clopidogrel and reversed these molecular effects. However, NO blockade L-NAME weakened the protective effect and thus the molecular effects of BPC 157 on gastric mucosa. In conclusion, these results suggest that BPC 157 inhibited Clopidogrel-induced gastric mucosa injury partially by inhibition of gastric mucosa cell ER stress-mediated apoptosis and inflammation, and promoting gastric mucosa angiogenesis via <i>VEGF-A/VEGFR1</i> mediated-<i>AKT/p38/MAPK</i> signaling pathways.
Study Information
pubmed
2020
2020-12-21T00:00:00.000Z
10.2147/dddt.s284163