Portal hypertension and liver lesions in chronically alcohol drinking ratsprevented and reversed by stable gastric pentadecapeptide BPC 157 (PL-10, PLD-116), and propranolol, but not ranitidine

Liver lesions and portal hypertension in rats, following chronic alcohol ad ministration, are a particular target for therapy. Portal hypertension (mm Hg) assessed directly into the portal vein, and liver lesions induced by 7. 28 g/kg b.w, of alcohol given in drinking water for 3 months, were countera cted by a stable gastric pentadecapeptide BPC 157. GEPPPGKPADDAGLV, M.W.141 9, known to have a beneficial effect in a variety of models of gastrointest inal or liver lesions (10 mug or 10 ng/kg b.w. i.p. or i.g.) and propranolo l (10 mg/kg b.w. i.g.), but not ranitidine (10 mg/kg b.w. i.g.) or saline ( 5 ml/kg b.w. i.p./i.g.; control). The medication (once daily) was throughou t either the whole 3 months period (1) or the last month only (2) (last app lication 24 h before sacrifice). In the background of 7.28 g/kg/daily alcoh ol regimen similar lesions values were assessed in control rats following a lcohol consumption, after 2 or 3 months of drinking. Both prophylactic and therapeutic effects were shown. After a period of 2 or 3 months, in all con trol saline [intragastrically (i.g.) or intraperitoneally (i.p.)] treated r ats, the applied alcohol regimen consistently induced a significant rise of portal blood pressure values over values noted in healthy rats. In rats th at received gastric pentadecapeptide BPC 157 or propranolol the otherwise r aised portal pressure was reduced to the values noted in healthy rats. Besi des, a raised surface area (mum(2)) and increased circumference (mum) of he patocyte or hepatocyte nucleus [HE staining, measured using PC-compatibile program ISSA (VAMS, Zagreb, Croatia)] and an advanced steatosis [scored (0- 4), Oil Red staining] (on 100 randomly assigned hepatocytes per each liver) , an increased liver weight, all together parallel a raised portal pressure in controls. Some of them were completely eliminated (not different from h ealthy rats, i.e. portal pressure, the circumference and area of hepatocyte s, liver weight), while others were markedly attenuated (values less than i n drinking controls, still higher than in healthy rats, i.e. circumference and area of hepatocytes nucleus). On the other hand, ranitidine application attenuated only steatosis development. In summary, despite continuous chro nic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hyperten sion along with related liver disturbances. (C) 2001 Elsevier Science Ltd. All rights reserved.