M1274 Diclofenac Encephalopathy, Liver and Gastrointestinal Lesions in Rat and Stable Gastric Pentadecapeptide BPC 157

Abstract

Combined diclofenac encephalopathy, liver and gastrointestinal lesions have not yet been established in rats. The stable gastric pentadecapeptide, BPC 157 (GEPPPGKPADDAGLV, MW 1419, efficient in inflammatory bowel disease trials (PL 14736) and various wound treatment, no toxicity reported) is an anti-ulcer peptide with hepatoprotective effects that may also affectmany central disturbances. Diclofenac (12.5mg/kg)was given intraperitoneally once daily for 3 subsequent days. BPC 157 (10μg/kg, 10ng/kg) was given either (i) intraperi-toneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/ml, 0.16 ng/ml) up until the end of the experiment. At 3 h following the last diclofenac challenge, we evidenced severe gastric, intestinal and liver lesions, increased bilirubin, AST, ALT serum values, liver weight, prolonged sedation/unconsciousness (after any diclofenac challenge) and finally (hepatic) encephalopathy (Fig.1, C (control) B (BPC 157)). Brain edema was particularly present in the cerebral cortex and cerebellum, more in white than in gray matter, damaged (balloonized) red neurons were particularly expressed in the cerebral cortex and cerebellar nuclei, Purkinje cells and less expressed in hippocampal neurons. This was consistently counteracted in diclofenac-rats that received BPC 157 (μg- or ng-regimen, intraperitoneally or per-orally). In conclusion, the successful counteraction of combined diclofenac encephalopathy, liver and gastrointestinal lesions by BPC 157 regimens means that besides inflammatory bowel disease, diclofenac toxicity may be a new domain for possible BPC 157 therapy.