Učinak pentadekapeptida BPC-157, L - NAME i L - arginina na adjuvantni artritis u štakora posredovan NO - sustavom uz promjene na srcu i bubregu [Effect of pentadecapeptide BPC - 157, L - NAME and L - arginin on adjuvant arthritis in rats mediated by NO - system along with kidney and heart lesions]

Rukavina, Iva (2016) Učinak pentadekapeptida BPC-157, L - NAME i L - arginina na adjuvantni artritis u štakora posredovan NO - sustavom uz promjene na srcu i bubregu [Effect of pentadecapeptide BPC - 157, L - NAME and L - arginin on adjuvant arthritis in rats mediated by NO - system along with kidney and heart lesions]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Rheumatoid arthritis is a chronic inflammatory disease characterized by cartilage and bone destruction. It may affect internal organs as well, included heart and kidneys. The aim of the study is to establish BPC 157 antiinflammatory effect in adjuvant arthritis and to explore whether this effect related with NO - system. Materials and methods: The study was conducted on female Wistar rats, that were immunised with complete Freund’s adjuvat. We had two protocols (prophylactic and therapeutic) with 9 experimental groups each, treated with BPC 157 i.p. (10 μg/kg, 10 ng/kg) BPC 157, 10 μg/kg i 10 ng/kg, L arginin, L - NAME, BPC 157 10 μg/kg + L - NAME, L - NAME + L - arginin, L - arginin + BPC 157 10 μg/kg, L - arginin + L - NAME + BPC 157, 10 μg/kg and the control group treated with saline (5ml/kg i.p.). In prophylactic protocol animals were treated with above mentioned substances through 14 days. In therapeutic protocol we were initially waiting adjuvant arthritis symptoms to develop for 14 days and then started with treatment with above mentioned substances through the following 14 days (15 - 28 day). ECG was recorded after protocol ending and blood were taken for laboratory tests (AST, CK, LDH, urea, creatinin, sodium, potassium). Macroscopic and radiological analysis of joints, histological analysis of heart, kidneys and joints were done afterwards. Results: animals developed arthritis as well as myocarditis. BPC 157 abolished or completely counteracted all of these symptoms in both protocols and in all of the applied doses. L - NAME acted in the same way while L - Arginine aggravated the symptoms. Conclusion: BPC 157 has an anti inflammatory effect on adjuvanr arthritis and it is in relation with NO system.

Abstract in Croatian

Uvod: Reumatoidni artritis je kroniţna upalna bolest karakterizirana oštešenjem zglobne hrskavice, a moţe zahvatiti i unutarnje organe, ukljuţujuši srce i bubrege. Cilj: utvrditi protuupalni uţinak pentadekapeptida BPC 157 na modelu adjuvantnog artritisa u štakora te vidjeti da li se taj uţinak ostvaruje putem NO -sustava. Materijal i metode: istraţivanje je provedeno na ţenkama Wistar albino štakora koje su imunizirane Freundovim kompletnim adjuvansom. Podijeljeno je na dva protokola, profilaktiţki i terapijski, 9 skupina, 10 ţivotinja po skupini. U profilaktiţkom protokolu istraţivanja ţivotinje su svakodnevno kroz 14 dana primale sljedeše supstance: BPC 157 u dozama 10 μg/kg i 10 ng/kg, L arginin, L - NAME, BPC 157 u dozi 10 μg/kg + L - NAME, L - NAME + L - arginin, L - arginin + BPC 157 u dozi 10 μg/kg te posljednja skupina L - arginin + L - NAME + BPC 157 u dozi 10 μg/kg. U terapijskom protokolu, nakon imuniziranja Freundovim adjuvansom, kroz 2 tjedna je prašen razvoj artritisa. Terapijsko djelovanje zapoţeto je 14 - ti dan. Tada su sve skupine u vremenskom intervalu od naredna 2 tjedna svakodnevno primale iste supstance kao i u prvom dijelu istraţivanja. Po završetku oba protokola ţivotinjama je snimljen EKG te je uzeta krv za lab analizu (AST, CK, LDH, urea, kreatinin, Na, K). Svim ţivotinjama uţinjena je makroskopska procjena indeksa artritisa, histološka i radiološka analiza zglobova. Rezultati: Freundov adjuvans je 7 - 9 - ti dan doveo je do razvoja artritisa u štakora koji je ispoljio svoj maksimalan uţinak izmeŤu 12 - og i 14 - og dana. Tretirane ţivotinje su razvile i miokarditis. Simptomi artirtisa smanjili su se primjenom BPC 157 u obje ispitivane doze i u oba protokola, a protuupalno je djelovao i L- NAME, kako sam, tako i u kombinaciji s BPC 157. L - arginin je pogoršao simptome artiritsa i miokarditisa u oba potokola. Zaključak: BPC 157 je pokazao znaţajno protuupalno djelovanje kako u podruţju zglobova, tako je povoljno djelovao i na znakove miokarditisa. L - NAME je pokazao sinergistiţki uţinak sa BPC 157, dok je L - arginin pogoršao navedene simptome.

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