Abstract

We documented that stable gastric pentadecapeptide BPC 157 mitigates lithium‐induced intoxication in rats. BPC 157, LD1 not achieved, was implemented as an anti‐ulcer peptide in inflammatory bowel disease trials and now in a multiple sclerosis trial (Curr Pharm Des. 2018;24(18):1990–2001). Previously, BPC 157 counteracts consequences of dopamine (D), receptors blockade (neuroleptics‐induced catalepsy, prolonged QT intervals, sphincters dysfunction and gastric lesions), much like over‐stimulation (amphetamine acute and chronic disturbances; much like D‐receptors supersensitivity (amphetamine after haloperidol)), nigrostriatal lesions (MPTP Parkinsogenic neurotoxin), D‐vesicles depletion (reserpine) (see Sikiric et al., Brain‐gut axis and pentadecapeptide BPC 157: Theoretical and practical implications. Curr Neuropharmacol. 2016;14(8):857–865. Review.). Similarly, BPC 157 counteracts immobility more than imipramine in depression‐models (Porsolt's and chronic unpredictable stress‐open field) and induces 5‐HT release in particular brain areas (nigrostriatum) when given peripherally, acute and chronically (see Sikiric et al., Brain‐gut axis and pentadecapeptide BPC 157: Theoretical and practical implications. Curr Neuropharmacol. 2016;14(8):857–865. Review.). In this study, we applied lithium (500 mg/kg/day, intraperitoneally, once daily through 3 subsequent days). Medication (mg/kg) includes BPC 157(0.01; 0,00001), L‐NAME (5.0), L‐arginine (100.0), applied alone and /or together) while control rats received an equivolume of saline (5 mL/kg). Thereafter, at 20 minutes after medication, we assessed muscular weakness (score 1–5) during next 8 minutes. Then, for next 5 minutes, we recorded ECG. At 3 hours thereafter, the brain, heart, quadriceps muscle and diaphragm muscle were used for histopathological analysis. Regularly, lithium immediately produced severe syndrome (severe muscular weakness and prostration, reduced quadriceps muscle fibers and diaphragm, myocardial infarction, and edema of various brain areas, the most prominent in the cerebral cortex). The worsening appeared with subsequent applications. L‐NAME and L‐arginine, given separately, both induced severe aggravation. This aggravation disappeared when L‐NAME and L‐arginine were given together. Contrarily, given alone or together with NO‐agents, BPC 157 reduced muscular weakness and prostration and muscle damage and mitigated lithium induced myocardial damage. BPC 157 reduced nerve damage and brain edema.