Title:

Influence of hepatotoxic compounds on the molecular changes as well as DNA repairing mechanisms in hepatocytes

Author:

Abdel-Kader, Rania.

Subject:

fluvastatin ; necrosis ; apoptosis ; silymarin ; DDB

Abstract:

As experimental models are always needed to investigate the changes in hepatocytes under various liver damage conditions, fluvastatin was used in this thesis as a toxic agent in order to develop gradual and progressive liver damage. Fluvastatin was administered orally to male Wistar rats in doses: 25, 50, 75, and 100 mg/kg/day for 7 days. These toxic doses caused a condition resembles hepatitis, which disturbed rats ’body weight, serum glucose, serum triglycerides, and aminotransferases levels. In addition, fluvastatin toxicity directed injured hepatocytes elimination by two pathways necrosis and apoptosis, however, necrosis pattern accompanied with inflammatory liver condition was more predominant than apoptosis. Such challenging new experimental model helped in investigating the effect of two hepatoprotective drugs (Silymarin 140mg/kg/day and DDB 100mg/kg/day) on damaged hepatocytes. In addition, from results, both drugs showed a tendency to preserve hepatocyte membrane, and induce apoptotic cell elimination. However, they succeeded only at thelowest fluvastatin toxic dose (25 mg/kg/day), whereas at higher doses necrosis dominated. It can be concluded that fluvastatin can be used to establish rat experimental hepatitis model, and hepatoprotective drugs can be beneficial only if given as early as possible at the beginning of liver disease.

Place of publishing:

Krakow

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu trawiennego ; farmakologia

Degree grantor:

Jagiellonian University. Collegium Medicum. Faculty of Pharmacy.

Promoter:

Jerzy Jaśkiewicz

Date:

2012

Date issued:

2012

Type:

Praca doktorska

Format:

application/pdf

Call number:

ZB-118266

ControlNumberVIRTUA:

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Language:

eng

Access rights:

nieograniczony

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum