Table 1.
Sever encephalophaties and BPC 157
| Study | Noxious procedure | BPC 157 regimens | Assessed injured targets, which BPC 157 therapy beneficially affected |
|---|---|---|---|
| Ilic et al., 2011a | Diclofenac (12.5 mg/kg intraperitoneally, once daily for 3 days) inrats. | BPC 157 (10 μg/kg, 10 ng/kg) was strongly effective throughout the entire experiment when given (i) intraperitoneally immediately after diclofenac or (ii) per-orally in drinking water (0.16 μg/mL, 0.16ng/mL). | Gastrointestinal lesions |
| Severe gastricand intestinal lesions | |||
| Liver lesions | |||
| Pronounced parenchymal necrosis, extensive microvesicular steatosis, and sinusoidal dilation; increased bilirubin, aspartate transaminase (AST), alanine transaminase (ALT) serum values, increased liver weight. | |||
| Brain lesions | |||
| Prolonged sedation/unconsciousness, brain edema particularly located in the cerebral cortex and cerebellum, more in white than in gray matter, damaged red neurons, particularly in the cerebral cortex and cerebellar nuclei, Purkinje cells and less commonly inthe hippocampalneurons. | |||
| Ilic et al., 2010 | Paracetamol overdose (5 g/kg intraperitoneally) in rats | BPC 157 therapy (10 μg, 10 ng, 10 pg/kg, intraperitoneally or intragastrically) was effective (microg-ng range) against paracetamol toxicity, given in early (BPC 157 immediately after paracetamol, prophylactically) or advanced stage (BPC 157 at 3 hours after paracetamol, therapeutically). | Liver lesions |
| Increased ALT, AST, and ammonium serum values precede liver lesion, hepatomegaly. | |||
| Brain lesions | |||
| Neurons presented severe damage in several brain areas, Significant damage became apparent, accompanied by generalized convulsions. Edema was already present at 25 min following paracetamol application at the time of initiation of the generalized convulsions. | |||
| Ilic et al., 2009 | Insulin overdose (250 IU/kg i.p.) in rats | BPC 157 (10μg/kg) given (i) intraperitoneally or (ii) intragastrically immediately after insulin. | Gastrointestinal lesions |
| Severe gastriculcers | |||
| Liver lesions | |||
| Hepatomegaly, fatty liver, increased AST, ALT, amylase serum values, and liver glycogen breakdown with profound hypoglycemia and calcification development. Calcium deposits were present in the blood vessel walls, hepatocytes surrounding blood vessels, and sometimes even in the parenchyma of the liver, mainly as linear and only occasionally as granular accumulation. | |||
| Brain lesions | |||
| Seizures (eventually fatal), severely damaged neurons in thecerebral cortex and hippocampus. | |||
| Drmic et al., 2017 | Celecoxib (1 g/kg b.w. ip) in rats | Stable gastric pentadecapeptide BPC 157 (known to inhibit these lesions, 10 μg/kg, 10 ng/kg, or 1 ng/kg ip) and L-arginine (100 mg/kg ip), as well as NOS blockade (L-NAME) (5 mg/kg ip) given alone and/or combined immediately after celecoxib. | Gastrointestinal lesions |
| Severe gastriclesions | |||
| Liver lesions | |||
| Marked steatosis, congestion, and necrosis at 24 h and at 48 h, along with increased enzyme serum values. | |||
| Brain lesions | |||
| Brain edema was commonly absent, though damaged (balloonized) red neurons were markedly expressed, particularly in the cerebral cortex and in the Purkinje cells. | |||
| Ilic et al., 2011b | Chronic ibuprofen (0.4 g/kg intraperitoneally, once daily for 4 weeks) | Stable gastric pentadecapeptide BPC 157 (10 μg, 10 ng/kg) inhibited the pathology seen with ibuprofen (i) when given intraperitoneally, immediately after ibuprofen daily or (ii) when given in drinking water (0.16 μg, 0.16 ng/mL). | Gastrointestinal lesions |
| Severe gastriclesions | |||
| Liver lesions | |||
| Hepatomegaly, increased AST and ALT serum values with, and weight loss. | |||
| Brain lesions | |||
| Prolonged sedation/unconsciousness In particular, ibuprofen toxicity was brain edema, particularly in the cerebellum, with the white matter being more affected than in gray matter. In addition, damaged and red neurons, in the absence of anti-inflammatory reaction was observed, particularly in the cerebral cortex and cerebellar nuclei, but were also present, although to a lesser extent in the hippocampus, dentate nucleus, and Purkinje cells. | |||
| Lojo et al., 2016 | Immediately after anastomosis creation, shortbowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg) | BPC 157 (10 μg/kg or 10 ng/kg), L-NAME, 5 mg/kg, L-arginine (100 mg/kg) alone or combined, intraperitoneally, and assessed 24 h later. | Gastrointestinal lesions |
| Rats with surgery (short-bowel) alone exhibited mild stomach/duodenum lesions, while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract. | |||
| Liver lesions | |||
| Rats with surgery (short-bowel) alone exhibited considerable liver lesions, while those also administered diclofenac showed widespread severe liver lesions. | |||
| Brain lesions | |||
| Rats with surgery (short-bowel) alone exhibited severe cerebral/hippocampal lesions, while those also administered diclofenac showed widespread severe lesions in cerebellar nuclear/Purkinje cells and cerebrum/hippocampus. | |||
| Medvidovic- Grubisic et al., 2017 | Magnesium sulfate (560 mg/kgintraperitoneally) | Medication (given intraperitoneally/kg at 15 min before magnesium) [BPC 157 (10 μg, 10 ng), L-NAME (5 mg), L-arginine (100 mg), alone and/or together] in rats. | Muscle weakness, muscle lesions |
| Severe muscle weakness and prostration decreased muscle fibers in both quadriceps muscle and diaphragm. Rats that received either L-NAME or L-arginine as individual agents and then magnesium became feeble immediately after magnesium treatment and exhibited more muscle weakness and prostration. | |||
| Hypermagnesemia, hyperkalemia, increased serum enzyme values | |||
| Additionally increased hypermagnesemia, and newly emerged hyperkalemia (L-NAME or L- arginine). | |||
| Brain lesions | |||
| Prominent damage was observed in the cerebral cortex (also extended to cerebellar nuclei with both L-NAME and L-arginine). In HEK293 cells, the increasing magnesium concentration from 1 to 5 mM could depolarize the cells at 1.75 ± 0.44 mV. | |||
| Klicek et al., 2013 | Multiple sclerosis suited toxic rat model, cuprizone (compared with standard, a several times higher regimen, 2.5% of diet regimen + 1 g/kg intragastrically/day) | BPC 157 (in drinking water 0.16 μg or 0.16 ng/mL 12 mL/d/rat + 10 μg or 10 ng/kg intragastrically/day) till the sacrifice at day 4. | Muscle weakness |
| Cerebellar ataxia and impaired forelimb function. Control animals affected with cuprizone toxicity spare right forelimb, and thereby react only with one or no forelimb and have difficulty with maintaining body balance while rearing | |||
| Brain lesions | |||
| Cuprizone-controls clearly exhibited an exaggerated and accelerated damaging process; nerve damage appeared in various brain areas, with most prominent damage in the corpus callosum, laterodorsal thalamus, nucleus reunions, anterior horn motor neurons. |
To illustrate the pleiotropic beneficial effect of the BPC 157 therapy, we summarized the BPC 157 studies of the severe encephalopathis that affect various brain areas.