| Abstract | Istražen je učinak pentadekapeptida BPC 157 u modelima dopaminergičke neurotoksičnosti uzrokovane metamfetaminom; prvi je model uzrokovan jednom dozom metamfetamina (10, 20 ili 40 mg/kg), a drugi je model dopaminergičke preosjetljivosti u kojem se haloperidol daje tri dana prije metamfetamina. Ovakvi modeli korisni su istraživanju poremećaja razine dopamina u središnjem živčanom sustavu, posebno u nigrostrijatumu, koji rezultiraju smetnjama pri kretanju, kognitivnim procesima i ponašanju ljudi i životinja. Pokusi su provedeni na Wistar štakoricama kojima bi se prije metamfetamina ili haloperidola aplicirali BPC 157 ili fiziološka otopina. 24 h nakon aplikacije metamfetamina mjerila se lokomotorna aktivnost, bodovala poremećena motorika prednjih ekstremiteta i ataktični fenotip. Analizirala se razina malondialdehida (MDA) u mozgu 2 i 24 h nakon davanja metamfetamina, te broj neurona u strijatumu, supstanciji nigri i ventralnom tegmentalnom području 24 h nakon davanja metamfetamina. Štakorice koje su prije 10 mg/kg metamfetamine dobile BPC 157 bile su značajno aktivnije od kotrolnih štakorica 24 h nakon aplikacije metamfetamina. Štakorice koje su prije metamfetamina dobile BPC 157 imale su manje izražen ataktični fenotip i statistički značajno manje poremećenu funkciju prednjih ekstremiteta, veći broj zdravih, a manji broj patološki promijenjenih neurona u strijatumu, supstanciji nigri i ventralnom tegmentalnom području u odnosu na štakorice kontrolnih skupina. Dva sata nakon aplikacije metamfetamina razina MDA u strijatumu je bila značajno niža od fiziološke, dok je 24 h poslije bila viša. Kod štakorica tretiranih BPC-om 157 razina MDA u strijatumu bila je bliža fiziološkoj u svim slučajevima osim
24 h nakon aplikacije 40 mg/kg metamfetamina. U modelu dopaminergičke preosjetljivosti uzrokovane haloperidolom i metamfetaminom štakorice prethodno tretirane BPC-om 157 imale su manje razine MDA u strijatumu, hipokampusu i diencefalonu u odnosu na kontrolnu skupinu, a veću i sličniju fiziološkoj razinu MDA u malom mozgu. BPC 157 ima određeno neuroprotektivno djelovanje i štiti strijatum od dopaminergičke neurotoksičnosti uzrokovane metamfetaminom i potencirane haloperidolom, što upućuje na učinkovitost BPC-a 157 u prevenciji poremećaja razine dopamina, a moguće i Parkinsonove bolesti. |
| Abstract (english) | Introduction. The aim of the research was to invetigate the effect of pentadecapeptide BPC 157 in two rat models of metamphetamine - induced dopaminergic neurotoxicity. These models are useful in dopamine disorders research, especially regarding nigrostriatal dopaminergic neuron damage which results in movement disorders, cognitive and behavioural impairment in people and animals, with limited current therapy options.
Materials and methods. The first model was a simple, single - dose methamphetamine model (10, 20 ili 40 mg/kg), while the second one, the dopaminergic supersensitivity model, was potentianted with haloperidol (5 mg/kg) administered three days before methamphetamine (10 mg/kg). 106 Wistar female rats were used in both dopaminergic neurotoxicity models. Immediately after methamphetamine administration, their body temperature was monitored and stereotypies were counted. 24 hours after methamphetamine administration locomotor activity was measured, proximal forelimb function and atactic phenotype were scored. Healthy and damaged neurons were counted on hematoxylin- eosin stained sections of striatum, ventral tegmental area and substantia nigra pars compacta. MDA levels were measured in different brain regions; striatum, hippocampus, frontal cortex, cortex, diencephalon and cerebellum 2 and 24 hours after methamphetamine administration.
Results. In both models the average number of stereotypies was smaller in BPC 157 group in comparison to control group, but these differences were not statistically significant. BPC 157 did not decrease or prevent methamphetamine – induced hyperthermia. 24 hours after 10 mg/kg metamphetamine administration BPC 157 rats were significantly more active than control rats, while after higher methamphetamine doses these differences were present but not significant. In dopaminergic supersensitivity model BPC 157 rats were more active than control rats 24 and 48 h after haloperidol administration and all survived methamphetamine dose of 10 mg/kg given three days later, while two control rats died. In comparison with control group, BPC 157 rats had less pronounced atactic phenotype, significantly less impaired forelimb function, higher number of healthy and lower number of damaged neurons in striatum, ventral tegmental area and substantia nigra pars compacta. Two hours after methamphetamine administration MDA levels in striatum and other brain regions were lower than normal but increased above normal after 24 hours. BPC 157 rats had striatal MDA values closer to normal in every case except 24 hours after administration of 40 mg/kg methamphetamine. In latter hippocampal MDA values were higher in BPC 157 rats as well. In dopaminergic supersensitivity model BPC 157 rats had lower striatal, hippocampal and diencephalic MDA values and higher, but closer to normal, cerebellar MDA values.
Conclusion. BPC 157 had specific neuroprotective effect on striatum and prevented impairment od striatum-mediated motoric functions and striatal neuron loss, which implies efficacy of BPC 157 in parkinsonism prevention. |
