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Abstract
Recently, the pentadecapeptide BPC 157-induced counteraction of bupivacaine cardiotoxicity has been reported. Medication includes (i) lidocaine-induced local anesthesia via intraplantar application and axillary and spinal (L4-L5) intrathecal block, (ii) lidocaine-induced arrhythmias, (iii) convulsions, and (iv) lidocaine-induced HEK293 cell depolarisation. BPC 157 applications (intraplantar, intraperitoneal, and intragastric) were given (i) immediately after lidocaine, (ii) 10 min after, or (iii) 5 min before. The BPC 157/NO-system relationship was verified with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together, in axillary and spinal intrathecal blocks. BPC 157 applied immediately after lidocaine or 5 min before the application of lidocaine considerably ameliorated plantar presentation. BPC 157 medication considerably counteracted lidocaine-induced limb function failure; L-NAME was counteracted; L-arginine exhibited counteraction when given immediately after lidocaine, but prolongation was seen when given later. Given together, prophylactically or therapeutically, L-NAME and L-arginine (L-NAME + L-arginine) counteracted the other's response. BPC 157 maintained its original response when given together with L-NAME or L-arginine. When BPC 157 was given together with L-NAME and L-arginine, its original response reappeared. BPC 157 antagonised the lidocaine-induced bradycardia and eliminated tonic-clonic convulsions. Also, BPC 157 counteracted the lidocaine-induced depolarisation of HEK293 cells. Thus, BPC 157 has antidote activity in its own right against lidocaine and local anesthetics.
Highlights
We focused on the counteracting relationship between the stable gastric pentadecapeptide BPC 157 [1,2,3,4,5,6,7,8,9,10,11,12,13] and lidocaine, local anesthesia, infiltrative cutaneous analgesia, axillary and spinal intrathecal blocks, NO-system [1,2,3,4,5,6,7,8,9,10,11,12,13], lidocaine-induced arrhythmias, convulsions, and lidocaineinduced depolarisation in HEK293 cells
Specific arguments to extend the use of BPC 157 against the adverse effects of local anesthetics, such as lidocaine, follow the BPC 157 counteraction of bupivacaine cardiotoxicity [14], bupivacaine-induced depolarisation in HEK293 cells [14], and drug-induced heart arrhythmias [15,16,17,18,19]
We demonstrated that the stable gastric pentadecapeptide BPC 157 [1,2,3,4,5,6,7,8,9,10,11,12,13] strongly counteracts the local anesthetic effect of lidocaine, infiltrative cutaneous analgesia, and axillary and spinal intrathecal blocks. is counteracting effect is related to the NO-system, as shown by BPC 157 application with NO-agents, the NOS-blocker L-NAME and the NOS-substrate L-arginine, given alone and/or together
Summary
We focused on the counteracting relationship between the stable gastric pentadecapeptide BPC 157 [1,2,3,4,5,6,7,8,9,10,11,12,13] and lidocaine, local anesthesia, infiltrative cutaneous analgesia, axillary and spinal intrathecal blocks, NO-system [1,2,3,4,5,6,7,8,9,10,11,12,13], lidocaine-induced arrhythmias, convulsions, and lidocaineinduced depolarisation in HEK293 cells. Specific arguments to extend the use of BPC 157 against the adverse effects of local anesthetics, such as lidocaine, follow the BPC 157 counteraction of bupivacaine cardiotoxicity [14], bupivacaine-induced depolarisation in HEK293 cells [14], and drug-induced heart arrhythmias [15,16,17,18,19]. A particular extended BPC 157’s beneficial effect may combine the antagonism of the entire spectrum of local anesthetic-induced neurotoxic and cardiotoxic effects. Reported effective dose regimens of the pentadecapeptide BPC 157 [14,15,16,17,18,19], along with the NOS-inhibitor L-NAME and the NOS-substrate L-arginine, given alone and/or in combination, were administered after lidocaine application in rats or in an in vitro HEK293 cell model, showing the presence of endogenous voltage-gated potassium (K+), sodium (Na+), and calcium (Ca2+) channels [42]
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