engleski

Portal hypertension and liver lesions in chronically alcohol drinking rats prevented and reserved by stable gastric pentadecapeptide BPC 157(PL-10, PLD-116), and propranolol, but not ranitidinePortal

Liver lesions and portal hypertension in rats, following chronic alcohol administration, are particuiar 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 counteracted by a stable gastric pentadecapeptide BPC 157, GEPPGKPADDAGLV, M.W.1419, known to have beneficial effect in a variety of models of gastrointestinal or liver lesions(10 ľg or 10 ng/kg b.w. i.p. or i.g.)and propranolol (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 a daily)was throughout either the whole 3 months period(1) or the last month only(2)(last application 24 h before sacrifice).In the background of 7.28 g/kg/daily alcohol regimen similar lesions values were assessed in control rats following alcohol consumption, after 2 or 3 months of drinking.Both prophylactic and therapeutic effects werw shown.After a period of 2 or 3 months, in all control saline(intragastrically, i.g. or intraperitoneally, i.p.)treated rats, the applied alcohol regimen consistentently induced a sagnificant rise of portal blood pressure values over values noted in healthy rats.In rats that recived gastric pentadecapeptide BPC 157 or propranolol the otherwise raised portal pressure was reduced to the values noted in healthy rats.Besides, a raised surface area (ľm2) and increased circumference (micrometr)of hepatocyte 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, aii together parallel a raised portal pressure in controls.Some of them were completely eliminated(not different from healthy rats, i.e. portal pressure, the circumference and area of hepatocytes, liver weight), while others were markedly attenuated(values less than in drinking controls, still higher than ih healthy rats, i.e.circumference and area of hepatocytes nucleus).On the other hand, ranitidine application attenuated only steatosis development.In summary, despite continuous chronic alcohol drinking, pentadecapeptide BPC 157, and propranolol may prevent portal hypertension as well as reverse already established portal hypertension along with related liver disturbances.

pentadecapeptide BPC 157; rats; portal hypertension; liver lesion; chronically alcohol drinking

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