Učinak pentadekapeptida BPC 157 na tubularnu nekrozu u štakora izazvanu gentamicinom

Vukoja, Ivan (2019) Učinak pentadekapeptida BPC 157 na tubularnu nekrozu u štakora izazvanu gentamicinom. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: we have investigated the effect of pentadecapeptide BPC 157 on aminoglycoside nephrotoxicity (AN) in the rats after application of high dose of gentamicin. We assume that BPC 157 has nephroprotective effect by modulating overstimulative activity of iNOS in AN. Therefore we applied various combinations of L-NAME and L-arginin with BPC 157 and gentamicin. ----- Materials and methods: We have used male Wistar albino rats, body weight 150-200 grams. Rats have been randomized in 17 groups, 10 rats per group. Gentamicin in dose 100 mg/kg of body weight was administered to the rats in all groups. BPC 157 in attributable groups (AG) was administered intraperitoneally and per orally in AG. L-NAME, L-arginin and adequate combination were administered in AG. ----- Results: Clinical appearance was measured and scored, and score is significantly higher in all groups which were not been treated with BPC 157. Daily diuresis has been measured, polyuria is significantly higher and starts earlier in groups which are not treated with BPC 157, and anuric phase is not noted in BPC 157 treated rats. Significantly higher levels of creatinine and magnesium are noted in groups that are not treated with BPC 157. L-arginin raises creatinine values and concomitant L-arginin and L-NAME aggravates it more. Relative mass (RM) of kidney has been measured and results show higher RM in all groups that are not treated with BPC 157 which is probably caused by interstitial oedema. Finally, kidney samples will be patohystologicaly analysed and score is significantly better in BPC 157 treated rats. ----- Conclusion: we have proven that pentadecapeptide BPC 157 has a nephroprotective effect. BPC 157 decreases AN and mortality in AN which is evident in significantly better (p < 0,01) clinical status of the animal, absence of oliguric and anuric phase AN, lower creatinine, urea, calcium and magnesium levels, and PHD kidney findings showing either mild tubular lesions or virtually neat findings. BPC 157 effect is achieved by interference with the NO system, but also by other mechanisms that are not exclusively dependent on the NO system.

Abstract in Croatian

Uvod: istraživali smo učinak pentadekapeptida BPC 157 na aminoglikozidnu nefrotoksičnost (AOB) u štakora nakon primjene velike doze gentamicina. Pretpostavili smo da BPC 157 ima nefroprotektivni učinak moduliranjem pojačane aktivnosti iNOS-a u AOB. Stoga smo koristili različite kombinacije L-NAME i L-arginina s BPC 157 i gentamicinom. ----- Materijali i metode: Koristili smo muške Wistar albino štakore, tjelesne težine 150-200 grama. Štakori su randomizirani u 17 skupina, 10 štakora po skupini. Gentamicin u dozi 100 mg/kg tjelesne težine primijenjen je štakorima u svim skupinama. BPC 157 u odgovarajućim skupinama (OS) je primijenjen intraperitonealno i peroralno u OS, L-NAME i L-arginin i njihova kombinacija su primijenjeni u OS. ----- Rezultati: Klinički izgled mjeren je i ocijenjen, a rezultat je znatno veći u svim skupinama koje nisu bile tretirane s BPC 157. Mjerena je dnevna diureza, poliurija je znatno veća i počinje ranije u skupinama koje nisu tretirane BPC 157, a anurična faza nije zabilježena kod štakora tretiranih s BPC 157. Značajno više razine kreatinina i magnezija su zabilježene u skupinama koje nisu tretirane s BPC 157. L-arginin povećava vrijednosti kreatinina, a L-arginin i L-NAME istodobno ga dodatno pogoršavaju. Relativna masa (RM) bubrega izmjerena je i rezultati pokazuju veću RM u svim skupinama koje nisu tretirane BPC 157, što je vjerojatno uzrokovano intersticijskim edemom. Konačno, uzorci bubrega su patohistološki analizirani i rezultati su značajno bolji kod štakora tretiranih s BPC 157. ----- Zaključak: dokazali smo da pentadekapeptid BPC 157 ima nefroprotektivni učinak. BPC 157 smanjuje AOB i smrtnost u AOB koji je vidljiv u značajno boljem (p <0,01) kliničkom statusu životinje, izostanku oligurije i anurične faze AOB, nižim razinama kreatinina, ureje, kalcija i magnezija, dok PHD nalaz pokazuje blage tubularne ozljede ili praktički uredne nalaze. BPC 157 učinak ostvaruje interferiranjem sa NO sustavom, ali i drugim mehanizmima koji nisu ovisni isključivo o NO sustavu.

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