Possible protective effect of an irradiated scorpion venom bioactive protein against doxorubicin-induced cardiotoxicity in rats / Fatma Yehia Abdou Abdelhamid ; Supervised Afaf A. Ain Shoka , Esmat A. Shaaban , Lamiaa A. Ahmed Attia

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

The discovery of the bradykinin potentiating peptides (BPPs) led to the development of captopril, an ACE inhibitor derived from a peptide found in the venom of the lancehead viper Bothropsjararaca. Nowadays, millions of hypertensive patients worldwide are treated with ACE inhibitors. In the present study, BPP isolated fromLeiurusquinquestriatus(Lq) scorpion venom was dissolved in saline, and then irradiated with 2 kGy gamma rays.The possible protective effect of native and irradiated isolated fractions with bradykinin potentiating activity (BPA) from Lq scorpionvenom were investigated against doxorubicin-induced acute cardiotoxicity (15 mg/kg, i.p.) on the 21st day of the experimentin rats.Native and irradiated fraction with BPA isolated from scorpion venom, were administered (1 o g/g,i.p.) twice per week for 3 weeks. At the end of experiment,ECG monitoring was performed.Rats werethensacrificed and serum was separated for determination of serum troponin T (cTnT) and lactate dehydrogenase (LDH) levels. Moreover, some biochemical parameters were selected to be measured in heart homogenate in this study include, the assessment of oxidative stress markers;lipid peroxidation products (TBARS), glutathione reductase(GR), superoxide dismutase (SOD) and catalase (CAT).In addition, inflammatory markers ; TNF-Ü , IL-1, IL-6,nitric oxide (NO)levels,vascular endothelial growth factor (VEGF),transforming growth factor-b (TGF-Ý), NF-mB p65 subunit, endothelial and inducible nitric oxide synthase (e NOS, i NOS) protein expression were determined.Furthermore, apoptotic markers;caspase-3, caspase-9, bax, bcl2 and cytochrome c were measured

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