Introduction
The stable gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGALV, M.W.1419), which has a very safe clinical profile, is promising against inflammatory bowel disease (clinical phase II, PL-10, PLD-116, PL-14736, Pliva), (i.e., Sikiric et al., 1994, Sikiric et al., 1997, Sikiric et al., 1999, Veljaca et al., 2002). Previously, it was shown to counteract and reverse damage induced by acute and chronic alcohol ingestion in stomach and liver (including portal hypertension) (Sikiric et al., 1994, Sikiric et al., 1997, Prkacin et al., 2001a, Prkacin et al., 2001b, Prkacin et al., 2002), and also, when given peripherally, to affect various disturbances supposed to be centrally mediated (Jelovac et al., 1998, Jelovac et al., 1999; Sikiric et al., 1999, 2000, 2001, 2002). We hypothesized that it may have a beneficial effect against acute alcohol intoxication or withdrawal following chronic consumption. We thus tested BPC 157 in dose regimens used previously (Jelovac et al., 1998, Jelovac et al., 1999; Sikiric et al., 1994, 1997, 1999, 2000, 2001, 2002; Prkacin et al., 2001a, Prkacin et al., 2001b, Prkacin et al., 2002) and administered the drug intraperitoneally (i.p.) or intragastrically (i.g).
Section snippets
Materials and method
Male NMRI mice (25–30g, kept at 22 °C ±1–2 °C, 12-h light dark cycle, food and water ad libitum, randomly assigned for experiments, approved by local ethic committee, assessed by an observer blind about treatment) were subjected to either (i) acute alcohol (4 g/kg i.p.)) intoxication or (ii) 20%-alcohol drinking (7.6 g/kg) for 13 days, with withdrawal provocation on the 14th day. (i) We applied saline (5 ml/kg) or BPC 157 (manufactured by Diagen, d.o.o., Ljubljana, Slovenia) (10 pg i.p., 10 ng
Results
In mice that were either acutely intoxicated or physically dependent on alcohol, BPC 157 intraperitoneally or intragastrically strongly prevented the effects of acute intoxication (i.e., quickly produced and sustained anesthesia, hypothermia, increased ethanol blood values, 25% fatality, 90-min assessment period) when given before or after ethanol, and none of the mice died (Table 1). When given after abrupt cessation of chronic ethanol (at 0 or 3 h withdrawal time), it attenuated withdrawal
Discussion
The pharmacological effects of ethanol are non-selective, in as much as alcohol can affect membrane organization, the function of membrane-bound enzymes, enzymes and proteins involved in signal transduction, ion channels, receptor-coupled ionophores, carrier proteins and gene expression (Fadda and Rossetti, 1998). In contrast, its effects are specific in as much as ethanol interacts with discrete sites on particular proteins that are critical for protein function and for cell functioning (Fadda