MLK3 Signaling Stimulates Intestinal Mucosal Healing

Stable gastric pentadecapeptide BPC 157 (an anti-ulcer peptide effective in IBD trials, LD1 not achieved) counteracted short bowel syndrome (Sever et al., Dig Dis Sci, 2009) and protected rats against diclofenac gastrointestinal injuries (Ilic et al., J Physiol Pharmacol, 2009). Aim: In this study we tested the effect of pentadecapeptide 157 on induced short bowel syndrome rats aggravated with high dose of diclofenac. Material and methodsWe used 80%-small intestine resection and then short bowel syndrome rats received diclofenac application (12.5 mg/kg i.p.). Medication (BPC 157 10 μg/kg or an equivolume of saline (5 ml/kg ip) was given immediately after diclofenac. Animals were sacrificed 24 h after the surgery. Assessment included bleeding period (sec), gastrointestinal lesions (sum of longest diameters of lesions stomach, small and large intestine), serumAST, ALT, bilirubine levels. Microscopic analysis was also performed. Results All BPC 157 treated animals had shorter bleeding period compared to control group animals (210 +/37s vrs. 480 +/43 s). Bilirubine levels were significantly increased in control group animals compared to BPC 157 treated animals ( 192.3 +/46.7 μmol/ L vrs 6.8+/3.1 μmol/L). AST, ALT, LDH were increased in both tested groups (AST: 308+/-14 u/L (BPC157) vrs 383+/-27 u/L (con.); ALT: 52+/-4 u/L (BPC157) vrs 63+/-6 u/L (con.)) Number of gastrointestinal lesions (gastric, duodenal, small and large intestinal ulcerations) was significantly larger in control animal group compared to BPC 157 treated animals (gastric: 5.6 +/2.7 lesions (con) vrs . 0.5+/0.2 lesions (BPC); duodenal (1.3 +/-0.2 lesions(con) vrs 0 lesions (BPC); jejunum, ileum and rectum score (1ulcerations, 2erosions and erithema, 3normal mucosal surface); Jejunum: 1.6+/0,7(con) vrs 2.8+/-0.2 (BPC); Ileum: 1 +/0,4 (con) vrs 2.8+/-2 (BPC); Rectum 1+/-0.3 (con) vrs 2.6 +/0,4 (BPC)). Conclusion According to our results we could conclude that BPC 157 improves small bowel and liver lesions healing in malnutrition conditions even during high dose diclofenac exposure.