The protection of the myocardium by amifostine against mitoxantrone-induced acute cardiotoxicity in rats

Autor:	Hülya Aybek, Vefki Gürhan Kadıköylü, Zahit Bolaman, Süleyman Demir, Mete Kalak, Muharrem Balkaya, Cigdem Yenisey, Ibrahim Meteoglu
Rok vydání:	2016
Předmět:	acute cardiotoxicity degeneration Pharmacology Lipid peroxidation chemistry.chemical_compound creatine kinase blood level rat glutathione glutathione peroxidase acute disease chemistry.chemical_classification troponin T biology Glutathione peroxidase catalase malonaldehyde apoptosis article lipid peroxidation Hematology Amifostine lcsh:Diseases of the blood and blood-forming organs Malondialdehyde superoxide dismutase creatine kinase MB sodium chloride histopathology medicine.drug lcsh:Internal medicine animal experiment cardiotoxicity mitoxantrone animal tissue heart protection enzyme blood level Superoxide dismutase male medicine controlled study cardiovascular diseases lcsh:RC31-1245 Creatinine Cardiotoxicity calcium nonhuman business.industry lcsh:RC633-647.5 animal model fibrosis Acute cardiotoxicity Glutathione chemistry inflammation protein blood level biology.protein business
Zdroj:	Turkish Journal of Hematology, Vol 27, Iss 02, Pp 62-69 (2010)
ISSN:	1300-7777
Popis:	Amifostine (AMI) has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO)-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations.Thirty-six rats were divided into six groups (n=6 in each). Control rats were given intraperitoneal (i.p.) serum saline and AMI group rats were given 200 mg/kg AMI i.p. Rats received MITO-2.5 and 5 mg/kg i.p. in the MITO-2.5 and MITO-5 groups. AMI 200 mg/kg i.p. was administered 30 min. before the same doses of MITO in the MITO-2.5+AMI and MITO-5+AMI groups.The levels of cardiac enzymes such as creatinine phosphokinase-myocardial band and cardiac troponin T did not change. Malondialdehyde (MDA) levels increased in MITO groups compared to controls. Catalase and glutathione (GSH) levels in the MITO and MITO+AMI groups were higher than in controls. Superoxide dismutase and glutathione peroxidase levels were not different between MITO groups and controls. There was no difference in MDA levels between MITO+AMI groups and controls. Calcium deposition was not detected. The scores of fibrosis, apoptosis, inflammation, and degeneration in MITO groups were higher than in controls. The scores of fibrosis, degeneration and inflammation in MITO+AMI groups were lower.MITO caused lipid peroxidation and myocardial damage, and the myocardium increased catalase and GSH levels to prevent this damage. AMI can protect against MITO-induced acute cardiotoxicity, decreasing myocardial damage and lipid peroxidation.AMAÇ: Amifostin (AMI) doksorubisinin yol açtığı kardiyotoksisiteden korunmada çeşitli deneysel ve bir kaç klinik çalışmada kullanılmıştır. Bu çalışmanın amacı Sıçan kalbindeki lipid peroksidasyonu, koruyucu enzimler ve mitoksantronun (MITO) yol açtığı akut kardiyotoksisite üzerinde AMI’nin etkilerini biyokimyasal ve histopatolojik incelemeler ile araştırmaktı. YÖNTEMLER: Her bir grupta 6 sıçan olmak üzere 36 sıçan 6 gruba bölündü. İntraperitoneal (ip) olarak kontrol grubuna serum fizyolojik ve AMI grubuna 200 mg/kg AMI verildi. MITO 2.5 ve 5 gruplarındaki sıçanlar ip MITO 2.5 ve 5 mg/kg aldı. MITO 2.5+AMI ve MITO 5+AMI gruplarında aynı dozlarda MITO’dan 30 dk önce 200 mg/kg AMI uygulandı.Kretainin fosfokinaz-miyokardial bant ve kardiyak troponin T gibi kardiyak enzimlerin düzeyi değişiklik göstermedi. MITO gruplarındaki malondialdehid (MDA) düzeyleri kontrollere kıyasla yüksekti. MITO ve MITO+AMI gruplarındaki katalaz ve glutatyon düzeyleri kontrollerden yüksekti. MITO+AMI ve kontroller arasında süperoksit dismutaz ve glutatyon peroksidaz düzeyleri bakımından fark yoktu. Kalsiyum birikimi saptanmadı. Fibrozis, dejenerasyon ve inflamasyon skorları MITO+AMI gruplarında daha düşüktü. SONUÇ: MITO lipid peroksidasyonu ve miyokardiyal zaralanmaya neden olurken miyokardiyum bu zaralanmadan korunmak için katalaz ve GSH düzeylerini arttırmaktadır. AMI miyokardiyal zararlanma ve lipid peroksidasyonu azaltarak MITO’nun yol açtığı akut kardiyotoksisiteye karşı koruyucu olabilmektedir.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::299c8bbac281c4010c764afb78180941 https://pubmed.ncbi.nlm.nih.gov/27263446 Zobrazit plný text záznamu