Stable gastric pentadecapeptide BPC 157 in the treatment of colitis and ischemia and reperfusion in rats: New insights

Abstract

AIMTo provide new insights in treatment of colitis and ischemia and reperfusion in rats using stable gastric pentadecapeptide BPC 157.METHODSMedication [BPC 157, L-NAME, L-arginine (alone/combined), saline] was bath at the blood deprived colon segment. During reperfusion, medication was BPC 157 or saline. We recorded (USB microscope camera) vessel presentation through next 15 min of ischemic colitis (IC-rats) or reperfusion (removed ligations) (IC + RL-rats); oxidative stress as MDA (increased (IC- and IC + RL-rats)) and NO levels (decreased (IC-rats); increased (IC + RL-rats)) in colon tissue. IC + OB-rats [IC-rats had additional colon obstruction (OB)] for 3 d (IC + OB-rats), then received BPC 157 bath.RESULTSCommonly, in colon segment (25 mm, 2 ligations on left colic artery and vein, 3 arcade vessels within ligated segment), in IC-, IC + RL-, IC + OB-rats, BPC 157 (10 μg/kg) bath (1 mL/rat) increased vessel presentation, inside/outside arcade interconnections quickly reappeared, mucosal folds were preserved and the pale areas were small and markedly reduced. BPC 157 counteracted worsening effects induced by L-NAME (5 mg) and L-arginine (100 mg). MDA- and NO-levels were normal in BPC 157 treated IC-rats and IC + RL-rats. In addition, on day 10, BPC 157-treated IC + OB-rats presented almost completely spared mucosa with very small pale areas and no gross mucosal defects; the treated colon segment was of normal diameter, and only small adhesions were present.CONCLUSIONBPC 157 is a fundamental treatment that quickly restores blood supply to the ischemically injured area and rapidly activates collaterals. This effect involves the NO system.

Stable gastric pentadecapeptide BPC 157 in honeybee (Apis mellifera) therapy, to control Nosema ceranae invasions in apiary conditions

“…Therefore, the antioxidant system may play an essential role during midgut invasion, which is however, largely disabled in invaded honeybees (Dussaubat et al., ). Thus, although this was not specifically investigated in insect midgut, it should be noted that various free radicals‐induced lesions in other organs were also counteracted by BPC 157 administration (Ilic et al., ; Luetic et al., ; Sikiric, Seiwerth, et al., ), and in particular, ischemia/reperfusion injuries in rat colitis (Duzel et al., ). Thus, it was suggested that BPC 157 may serve as a possible antioxidant (i.e., BPC 157 contains four carboxylic groups, all of them could be active in scavenger process and if reactivated [e.g., by glutathione or by enzymes], the overall beneficial activity could be very high; Duzel et al., ).…”

“…Thus, although this was not specifically investigated in insect midgut, it should be noted that various free radicals‐induced lesions in other organs were also counteracted by BPC 157 administration (Ilic et al., ; Luetic et al., ; Sikiric, Seiwerth, et al., ), and in particular, ischemia/reperfusion injuries in rat colitis (Duzel et al., ). Thus, it was suggested that BPC 157 may serve as a possible antioxidant (i.e., BPC 157 contains four carboxylic groups, all of them could be active in scavenger process and if reactivated [e.g., by glutathione or by enzymes], the overall beneficial activity could be very high; Duzel et al., ). Additionally, as suggested (Duzel et al., ), BPC 157 is present in the most body tissues where can catch reactive free radicals and inactivate them on crucial positions where other antioxidants cannot reach (Sikiric, Petek, et al., ).…”

“…However, the optimal manner of application of this potential dietary supplement for regular use should be adapted to the optimum concentration and treatment replications, actual working conditions of the individual beekeeper (Botias, Martin‐Hernandez, Meana, & Higes, ), and other zootechnical or environmental factors, before can be used within honeybee colonies disease control management programs. It is, however, noteworthy, that one single initial application may induce a prolonged beneficial effect in ischemia/reperfusion injuries in rat colitis (Duzel et al., ). Nevertheless, considering the chances of approval of this drug for apicultural use in the EU, these findings seem to be favorable with respect to several other alternative products that have been evaluated as possible treatments to control nosemosis in field conditions, for example preparations with the herbal basis (Bekesi, Szalai Matray, Harka, Hegedus, & Albert, ; Chioveanu, Ionescu, & Mardare, ; Maistrello et al., ; Nanetti, ; Tlak Gajger et al., ; Tlak Gajger, Vugrek, Pinter, & Petrinec, ; Tlak Gajger, Petrinec, Pinter, & Kozarić, ), mineral compounds (Tlak Gajger et al., ) or animal lysozymes and essential oils extracted from Vetiveria zizanioides (Maistrello et al., ), with varying effects which were similar or less effective in comparison with BPC 157.…”

“…On the other hand, BPC 157 is an anti‐ulcer peptide used in trials for ulcerative colitis and now is in trials for the treatment of multiple sclerosis that largely interacts with NO‐system and is thought to be novel mediator of Robert's cytoprotection in rat studies (Sikiric et al., , , ). Thereby, BPC 157 exerts endothelium and mucosal protection in stomach, counteracts variously induced gastrointestinal lesions in different species (Duzel et al., ; Sikiric et al., , , , ), but has not been tested in social insects. Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al., ; Chang, Tsai, Hsu, & Pang, ; Chang, Tsai, Lin, Hsu, & Pang, ; Hsieh et al., ; Huang et al., ; Tkalcevic et al., ).…”

“…Several molecular pathways are discussed as possible targets of BPC 157 (Cesarec et al, 2012;Chang, Tsai, Hsu, & Pang, 2014;Chang, Tsai, Lin, Hsu, & Pang, 2011;Hsieh et al, 2017;Huang et al, 2015;Tkalcevic et al, 2007). Thereby, BPC 157 was considered to be suitable for the extension of the beneficial effect to the entire gastrointestinal tract Sikiric et al, 2010Sikiric et al, , 2012Sikiric et al, , 2014Sikiric et al, , 2017Sikiric et al, 2011Sikiric et al, , 2013Sikiric et al, , 2016Duzel et al, 2017).…”