Učinak pentadekapeptida BPC 157 i losartana na nefrotoksičnost epirubicina u eksperimentalnih životinja

Ćorić-Martinović, Valentina (2012) Učinak pentadekapeptida BPC 157 i losartana na nefrotoksičnost epirubicina u eksperimentalnih životinja. PhD thesis, Sveučilište u Zagrebu.

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Abstract

We focused on epirubicin induced progressive renal failure and the effects of stable gastric pentadecapeptide BPC 157 and losartan. In rats and mouses epirubicin 5 mg/kg was used intraperitoneally. Thereafter, all the animals were randomly assigned for two subsequent protocols: in co-treatment protocol with treatment started immediatly after randomisation and in post-treatment protocol with treatment started 7 days after epirubicin injection. We used for medication: losartan (1 mg/kg and 10 mg/kg) and BPC 157 (10 pg/kg, 10 ng/kg, 10 micro g/kg) given intragastric once daily (rats) or in drinking water (mice, 2 ml/mouse daily), while controls received an equivolumen of distilled water (rats, 5.0 ml/kg, i.g.) or drinking water (mice). The animals were sacrificed 28 days after epirubicin application. Seven days following epirubicin regimen, control animals (without treatment) have a signs of nephrotic syndrome (proteinuria, hyperlipidaemia and edema) with specific differences between species. These signs developed in control groups in 14. and 28. day. Losartan showed expected beneficial effects on signs of nephrotic syndrome. BPC 157 showed better and more rapid effect than losartan on hystopathological changes, proteinuria, hyperlipidaemia and edema in present study. Control animals had focal epitel necrosis of proximal tubule in significantly higher stage then animals treated with losartan. Animals treated with BPC 157 did not have pathological changes. These results are in correlation with beneficial effect of BPC-157 on doxorubicine induced congestive heart failure and suggest use of BPC 157 in treatment of nephrotic syndrome.

Abstract in Croatian

U radu su prikazani učinci pentadekapeptida BPC 157 i losartana u eksperimentalnom modelu nefrotskog sindroma izazvanog primjenom epirubicina u štakora i miša. Nefrotski sindrom izazvan je jednokratnom intraperitonealnom primjenom epirubicina u dozi od 5 mg/kg TT. Eksperimentalne životinje su podijeljene u dvije skupine: kotretman, za koje je tretman započeo neposredno nakon aplikacije epirubicina, i posttretman, za kojih je tretman započeo 7 dana nakon aplikacije epirubicina. Životinje su svakodnevno tretirane intragastrički (štakori) ili u vodi za piće (miševi) losartanom u dozama 1 mg/kg i 10 mg/kg i pentadekapeptidom u dozama BPC-a 157 10 pg/ml, 10 ng/ml i 10 mikro g/kg, a žrtvovane su 28 dana nakon aplikacije epirubicina. Dobiveni su sljedeći rezultati: u kontrolnim skupinama neliječene su životinje imale izražene znakove nefrotskog sindroma u smislu edema s proteinurijom i hiperlipidemijom u značajno većoj mjeri od tretiranih životinja. Losartan je pokazao očekivani povoljan učinak na te znakove nefrotskog sindroma. BPC 157 je pokazao bolji i raniji učinak na proteinuriju i posljedične periferne edeme te hiperlipidemiju od losartana. Učinci su bili izraženiji primjenom mikrogramske doze. Histopatološka analiza također je pokazala povoljan učinak BPC-a 157 na potpuni izostanak promjena, a losartana na značajno manju pojavu promjena u usporedbi s kontrolom. Ti su rezultati u korelaciji s povoljnim učinkom BPC-a 157 na doksorubicinom izazvano kongestivno srčano zatajenje i sugeriraju njegovu upotrebu u liječenju nefrotskog sindroma.

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