1. PATHOLOGICAL STUDIES ON INDUCED HEPATIC CIRRHOSIS WITH EVALUATION OF SOME HEPATOPROTECTIVE MATERIALS IN RATS PhD 2016

2. بسم الله الرحمن الرحيم "قَالُواْ سُبْحَانَكَ لاَ عِلْمَ لَنَا إِلاَّ مَا عَلَّمْتَنَا إِنَّكَ أَنتَ الْعَلِيمُ الْحَكِيمُ " – (32)- البقرة

3. PATHOLOGICAL STUDIES ON INDUCED HEPATIC CIRRHOSIS WITH EVALUATION OF SOME HEPATOPROTECTIVE MATERIALS IN RATS Asmaa Khairy Mohammed Al-Mokaddem MSc. (2013) Prof. Dr. Sahar Samir Mahmoud Prof. of pathology Faculty of veterinary medicine Cairo University Prof. Dr. Kawkab Abd El Aziz Ahmed Prof. of pathology Faculty of veterinary medicine Cairo University Supervision

4. Introduction

5. – The liver is one of the most important organs of the body. It performs a fundamental role in the regulation of diverse physiological processes, and its activity is related to different vital functions, such as metabolism, secretion, and storage. – Cirrhosis is a diffuse disorganization of normal hepatic structure by extensive fibrosis associated with regenerative nodules. Advanced cirrhosis leads to major alterations in the hepatic vascular bed and is usually irreversible – Fibrosis consists of the accumulation of extracellular matrix (ECM) proteins, mainly fibrillar collagen, as the result of both increased ECM synthesis and decreased degradation of matrix.

6. Vascular and architectural alterations in Cirrhosis

7. Interventions in Cirrhosis management – There is no standard treatment for liver fibrosis, there are several therapeutic approaches to control liver fibrosis. – The ideal antifibrotic therapy would be one that is liver-specific, well tolerated when administered for prolonged periods of time, and effective in attenuating excessive collagen deposition without affecting normal ECM synthesis – Antioxidants are the most promising drugs in treatment or prevention of liver fibrosis. They inhibit HSC activation, protect hepatocytes.

8. Natural products with Hepatoprotective effect 1 Silymarin (Silybum marianum)

9. Natural products with Hepatoprotective effect 2 Propolis (Bee Glue)

10. Natural products with Hepatoprotective effect 3 Spirulina (Spirulina platensis)

11. Natural products with Hepatoprotective effect 4 Naringenin

12. Aim of Work 1.Histopathological examination and scoring of TAA- Induced hepatic cirrhosis as a reliable model of experimentally induced cirrhosis and correlation between histopathological scores and serum biomarkers. 2. Evaluation of the hepatoprotective effects of some natural agents (Silymarin, Propolis, Spirulina and Naringenin) against TAA-induced hepatic cirrhosis.

13. Materials & Methods

14. Thioacetamide (TAA) 200 mg/kg.Bwt – Twice/ week 1 + Distilled Water 2 Silymarin 100 mg/kg.Bwt – Daily 3 Propolis 100 mg/kg.Bwt – Daily 4 Spirulina 300 mg/kg.Bwt – Daily 5 Naringenin 50 mg/kg.Bwt – Daily (Chemicals)

15. Materials & Methods (Animals)

16. G. No. TAA SilymarinPropolisSpirulinaNaringenin I 30----- II 30--- III 30--- IV 30--- V --- VI 30---- VII 30--- VIII 30--- IX 30--- X ---

17. Materials & Methods (Samples) Sacrificed weekly Samples

18. Materials & Methods (Samples) Samples Blood Serum Liver Function tests (AST, AlP, GGT) Kidney Function tests (BUN, Creatinine)

19. Materials & Methods (Samples) Samples Liver -20 o C 10% NBF

20. Materials & Methods (Samples) Samples Preserved in 10% NBFFrozen Samples Routine H&E stain. MTC Stain Immunohistochemistry: -α- Smooth Muscle actin -Apoptotic protein Bcl-2 and caspase-3expression -collagen type III Assessment of oxidative stress markers Malondialdehyde, catalase activity and GSH