Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Methods : animals were randomly allocated into five groups (6 rats in each group). Group1 (Control group): animals in this group served as normal control group and received distilled water p.o. daily for 3 days, Group2 (APAP group): animals in this group received one single dose of APAP (1gm/kg, p.o), Groups 3 & 4 (SAC 100 & 200 groups): these animals were gavaged APAP (1gm/kg) orally and after 8 hrs they received SAC (100 or 200mg/kg, i.p), as a loading dose. After 4 hrs, animals receive half the dose (50 or 100mg/kg, i.p) as a maintenance dose then every 4 hrs for 3 days in a total of 18 doses, Group5 (NAC group): the rats in this group received APAP orally (1gm/kg), then after 8 hrs, they were administrated NAC (140mg/kg, i.p) as a loading dose. This was followed by the maintenance dose (70mg/kg i.p) four hrs later; this dose was repeated every 4 hrs for 3 days (18 doses). To induce APAP intoxication, male Wistar rats were gavaged APAP to induce toxicity. Paracetamol was suspended in distilled water to prepare a 10% solution to be administered orally in a dose of 1gm/kg. Serum samples were separated for determination of N-acetyl p-benzo quinone imine (NAPQI), alanine transaminase (ALT) and aspartate transaminase (AST). Liver was dissected to determine malondialdehyde (MDA) - glutathione (GSH), as measures of oxidative stress. Interlukin-6 (IL-6) and nuclear factor kappa (NF-m) B, as pro-inflammatory mediators. Apoptosis inducing factor (AIF), apoptosis factor caspase cleaved cytokeratin 18 fragment (M-30), GSK-3Ý/Ý-catenin, p-NF-mBp65 (at ser536) and cyclin D1 as indicators/regulators of pathways responsible for necrosis, apoptosis, proliferation, and differentiation. Also, histopathological examination is estimated

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