الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 135 |  |  |
| | | from | 135 | | |
Abstract
The liver is the largest organ of the mammalian body. It has a highly complex and specialized function that cannot be replaced by artificial equipment. The liver is a bidirectional bio-filter that maintains homeostasis of the body. It filters both portal and systemic blood (Michalopoulos, 2020).
NAFLD is one of the most important causes of liver disease worldwide in adults and children, with global prevalence about 24%. Patients with NAFLD have high-risk metabolic comorbidity (Majeed et al., 2020). Considering NASH as the most common form of histologically progressed NAFLD, it has a big interest of research (Kleiner and Makhlouf, 2016). NASH is a cause to elevate mortality rate in comparison with the general population (Zubrzycki et al., 2020).
Curcumin has wide availability, low cost, multi-target action, and potential safety (Rahnmani et al., 2016). It has a wide range of therapeutic actions; including antioxidant, anti-inflammatory, anticancer and lipid regulatory activities in vitro and animal models. It can suppress cellular oxidative stress and is well known anti-inflammatory agent (She et al., 2018).
Fenofibrate are PPARα agonists, they are considered the first-line drugs to reduce triglyceride levels (Kostapanos et al., 2013). They can act as proliferation inducers of peroxisomes in the liver (Rivera-Meza et al., 2017). Nrf2 is a master regulator that orchestrates gene expression for reduction of inflammation, oxidative stress, and fibrosis (Sharma et al., 2018). So, we compared the effect of both (curcumin and Fenofibrates) on NASH and their effect on Nrf2 expression.
A wide range of technique were used to fulfil the purpose of the study including; histological, histochemical and ultrastructural techniques. Moreover, various biochemical analysis and molecular biology techniques were used. The data were analyzed using scoring system and statistically analyzed.
In the current study, histological changes were examined in seven groups of rats (10 rats /group). group I (normal control) received normal diet. Experimental groups received HFD with or without treatments for 16 weeks include; group II (HFD + corn oil simultaneously), group III (HFD only), group IV (HFD + curcumin simultaneously), group V (HFD + Fenofibrate simultaneously), group VI (HFD followed by curcumin treatment for 2 weeks) and group VII (HFD followed by Fenofibrate treatment for 2 weeks).
The study revealed that:
A. Histological changes: curcumin administration (prophylactic and therapeutic) caused lesser damage to liver tissues with lesser inflammatory cellular infiltration, hepatocyte ballooning and cellular vacuolation. Fenofibrate administration (prophylactic and therapeutic) preserved hepatocyte histology and reduced lobular inflammatory infiltration and apoptotic cells. So curcumin and fenofibrate could have a potential prophylactic and therapeutic roles in NASH.
B. Histochemical assessment of collagen deposition and fibrotic changes: Both curcumin and fenofibrate have a potential prophylactic role in counteracting the fibrotic changes associated with NASH and almost abolishing fibrotic changes. However, their use following induction of NASH after the occurrence of the fibrosis did not completely abolish the fibrotic changes. Curcumin was far less effective than fenofibrate in reducing the fibrotic changes.
C. Ultrastructural study: curcumin and fenofibrate could have a potential prophylactic and therapeutic effects in NASH through preservation and restoration of the hepatocyte cellular and subcellular structures. Although they were effective in counteracting the fibrotic changes when used as prophylactic, they did not completely abolish the established fibrosis when used as therapeutic. Overall, therapeutic use improved the histological structure, but the liver was left with residual fibrotic changes particularly with curcumin.
D. NASH scoring: curcumin and fenofibrate significantly improved the NASH induced hepatic disorder with scores 3, 6, 3, and 3 for CP, CT, FP, and FT groups, respectively.
E. Biochemical assessment:
• Prophylactic administration of fenofibrate was more effective than curcumin in reducing body weight gain and its rate but increased liver index. They significantly reduced the biochemical profile changes.
• Therapeutic use of curcumin or fenofibrate following HFD significantly reduced body weight, liver index, ALT and AST serum levels and AST/ALT ratio. However, fenofibrate was more effective than curcumin.
F. Nrf2 gene assessment: Only therapeutic curcumin significantly increased Nrf2 gene expression. Administration of fenofibrate to HFD animals as prophylactic or therapeutic significantly increased Nrf2 gene more than CT group.
Consequently, the above data indicated that curcumin and fenofibrate have prophylactic and therapeutic effects against NASH through preservation and restoration of hepatocyte structure and functions, decreasing liver enzymes and NASH score. However, because of the possible side effects of fenofibrate curcumin would be relatively superior to recommend in prevention of NASH.