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العنوان
POSSIBLE ANTIFIBROTIC EFFECTS of FENOFIBRATE a PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR- AGONIST ALONE or COMBINED with PENTOXIFYLLINE in CONCANAVALIN A- INDUCED chrONIC HEPATITIS in RATS /
المؤلف
Mohamed, Doaa Ibrahem Mohamed.
هيئة الاعداد
باحث / Doaa Ibrahem Mohamed Mohamed
مشرف / Ahmed Abd El-Salam M. El-Melegy
مشرف / Lubna Fouad A. El-Aziz
مناقش / Hala Salah Abdel-Kawy
تاريخ النشر
2014.
عدد الصفحات
158p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
علم الأدوية (الطبية)
تاريخ الإجازة
1/1/2019
مكان الإجازة
جامعة عين شمس - كلية الطب - الادوية
الفهرس
Only 14 pages are availabe for public view

from 158

from 158

Abstract

SUMMARY AND CONCLUSION
hronic HCV infection is one of the most extensively studied conditions, and therapy (IFN-α plus ribavirin) with viral clearance results in fibrosis improvement. Importantly, nearly half of patients with fibrosis exhibit reversal to a significant degree. Whether this beneficial effect is associated with improvements in long-term clinical outcome, including decreased portal hypertension is unknown (Haider and Sherif, 2011).
It remains important to suppress progressive fibrosis and prevent the subsequent occurrence of HCC in patients who do not respond probably to IFNα and ribavirin therapy (Briana et al., 2012).
FF is widely used as a hypolipidemic drug that activates PPARα and thereby regulates the expression of a number of genes critical for lipid and lipoprotein metabolism, leading to lipid catabolism in the liver and reduction in total body fat as well as circulating plasma lipids. Pentoxifylline is a nonspecific phosphodiesterase inhibitor, it can increase the intracellular c-AMP and suppress TNF α gene transcription, expression and synthesis.Both drugs were proved to have anti-inflammatory and antioxidant effects.
The present work was conducted to investigate the possible anti fibrotic effects of FF (100mg/kg/day) and PTX (200mg/kg/day) either as a monotherapy and in combination on a model of chronic
C
Summary and Conclusion 
117
hepatitis induced by IVI of Con A (20mg/kg/week) for 8 weeks in male albino rats.
The following parameters were measured:
1. Portal pressure at the end of the 8th week.
2. Biochemical changes at the end of 1st,2nd, 4th and 8th weeks :
a. Serum ALT and AST.
b. Hepatic TNFα and MDA.
3. Histopathological and immunohistochemical studies at the end of the 1st, 2nd, 4th and 8th weeks.
4. Digital image analysis at the end of the 1st, 2nd, 4th and 8th weeks.
Results:
1. Portal pressure measurments.
Both FF and PTX either as a monotherapy or in combination produced significant decrease (p<0.05) in PP compared to Con A induced chronic hepatitis in rats which showed significant increase in PP (p<0.05) compared to control group. However, FF and PTX pretreated group produced more significant difference (p<0.05) from FF+PTX pretreated group at the end of the 8th week.
2. Biochemical results
Both FF and PTX either as a monotherapy and in combination produced significant reduction (p<0.05) of serum ALT and AST
Summary and Conclusion 
118
level compared to Con A induced chronic hepatitis in rats which showed significant elevation (p<0.05) of serum ALT and AST level compared to control group at the 1st, 2nd, 4th, 8th weeks. There was no significant difference between all pretreated groups.
Also, both FF and PTX either as a monotherapy or in combination produced significant reduction (p<0.05) of hepatic TNF α and MDA compared to Con A induced chronic hepatitis in rats which showed significant elevation (p<0.05) of hepatic TNF α and MDA compared to control group at the 1st, 2nd, 4th, 8th weeks. There was no significant difference between all pretreated groups early at the end of the 1st and 2nd weeks .While late, at the end of the 4th and 8th weeks, FF and PTX as a monotherapy produced more significant difference from FF+PTX pretreated group.
The combination of both drugs did not add a significant additional beneficial effect.
 Histopathology and immunohistochemistry results
FF pretreatment started early to improve the histopathological and immunohistochemical studies (anti-inflammatory, anti-fibrogenic effects through suppressing HSC activation, and apoptosis of nonparenchymal cells) in comparison to PTX pretreatment. On the other hand, combination therapy did not add a significant additional beneficial effect.
Summary and Conclusion 
119
Conclusion remarks:
It is concluded from the previous findings that, in a model of Con A induced chronic hepatitis in rats, FF or PTX pretreated groups produced significant decrease in all parameters measured (serum ALT and AST, hepatic TNFα and MDA and portal pressure). In addition FF pretreatment started early to improve the histopathological and immunohistochemical studies (anti-inflammatory, anti-fibrogenic effects through suppressing HSC activation, and apoptosis of nonparenchymal cells) in comparison to PTX pretreatment. On the other hand, combination therapy did not add a significant additional beneficial effect suggesting some sort of drugs interaction might occur and therapy with both drugs in the same frequency and doses need to be readjusted.
Recommendations:
 FF may represent a new therapeutic strategy for chronic hepatitis that needs further clinical study.
 Future studies are needed to evaluate higher doses of PTX (within the therapeutic level) and multiple frequent doses if combined with FF.
 Another liver function tests are needed; (serum albumin, total bilirubin, alkaline phosphatase, clotting time).Tissue hydroxyproline appears to be a more useful marker of fibrosis which is detected specifically in collagen and reflects the degree of hepatic fibrosis