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040 _aEG-GiCUC
_beng
_cEG-GiCUC
041 0 _aeng
049 _aDeposite
097 _aPh.D
099 _aCai01.08.09.Ph.D.2021.Ma.S
100 0 _aMalek Mohammed Mohsen Aziz
245 1 0 _aStudy of the protective effects of an angiotensin II receptor blocker and L-carnitine on doxorubicin-induced cardiorenal toxicity in rats /
_cMalek Mohammed Mohsen Aziz ; Supervised Helmy Moawad Sayed Ahmed , May Ahmed Galal
246 1 5 _aدراسة التأثيرات الوقائية لأحد غالقات مستقبل الانجيوتنسين-2 وال-كارنيتين في سمية القلب والكُلى بفعل دوكسوروبيسين فى الجرذان
260 _aCairo :
_bMalek Mohammed Mohsen Aziz ,
_c2021
300 _a171 P. :
_bcharts , facsimiles ;
_c25cm
502 _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology
520 _aBackground:Doxorubicin (DOX), an anthracycline antibiotic, is an important antineoplastic agent due to its high antitumor efficacy in haematological, as well as in solid malignancies. The clinical use of DOX is limited due to its cardiorenaltoxic side effects. Aim: The present study aimed to investigate the possible protective effect of olmesartan (Olm) or L-carnitine (L-CA) and their combination in cardiorenaltoxicity induced by Doxorubicin (DOX) in rats. Methods: Male albino rats were randomly divided into seven experimental groups (n=8): Group I: normal control, group II: L-CA, Group III: Olm, Group IV: DOX.The other three groups were treated with Olm, L-CA and their combination for 2 weeks, after induction of cardiorenaltoxicityby a single dose of DOX. On the last day of treatment, rats were anaesthetized with thiopental, then their echocardiograph (echo-c) was recorded and blood samples were collected to determine troponin I, creatine kinase-MB (CK-MB), lactate dehyclrogenase (LDH), creatinine (Cr), blood urea nitrogen (BUN) and kidney injury molecule-1 (KIM-1)in order to assess cardiac and renal functions. Furthermore, rats were sacrificed by cervical dislocation, and the heart and kidney were excised and homogenized to assess oxidative stress markers such as, reduced glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in both tissues.The proposed possible anti-inflammatory effects were investigated through determination of tumor necrosis factor-alpha (TNF-Ü), intercellular adhesion molecules-1(ICAM-1), interleukin IL-1Ý (IL-1 Ý), myeloperoxidase (MPO), nuclear factor- kappa B (NF-kB) and transforming growth factor Beta (TGF-Ý), which has emerged as having a key role in the development of cardiorenal hypertrophy.Furthermore, Immunohistochemical staining of caspase-3 in both heart and kidney tissues was performed, as key marker of apoptosis. Finally, histopathologicalexaminationsof both heart and renal tissues wereperformed. Results:DOXshowed a significant elevation in serum troponin I, CK-MB, LDH and creatinine, BUN as well as KIM-1. Moreover, DOXshowed a significant increase in TNF-Ü, ICAM-1, IL-1, MPO, NF-kB and TGF-Ýin both cardiac and renal tissues. While, DOX showed a significant increase in MDA and decrease in SOD and GSH in both heart and renal tissuesOn the other hand, administration of L-CA and Olm attenuated DOX-evoked disturbances in the above mentioned parameters
530 _aIssued also as CD
653 4 _aCardiorenal toxicity
653 4 _aDoxorubicin
653 4 _aL-carnitine
700 0 _aHelmy Moawad Sayed Ahmed ,
_eSupervisor
700 0 _aMay Ahmed Galal ,
_eSupervisor
856 _uhttp://172.23.153.220/th.pdf
905 _aNazla
_eRevisor
905 _aShimaa
_eCataloger
942 _2ddc
_cTH
999 _c80737
_d80737