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as indirect in vivo reliable indices for the contribution of enhancing antioxidant capacity in the liver of AZA-treated
free radical generation and in turn oxidative stress. It animals. This appeared from the amelioration of MDA to near
[37]
has already been demonstrated that the depletion of GSH normal level and the significant improvement of the GSH
precedes the induction of lipid peroxidation. [38] and TAC contents. These results agree with that reported
for chamomile flowers extract [48,49] and for fennel seeds
In this study, AZA-induced hepatotoxicity is evidenced by extract. [16,50]
significant increments in the values of serum ALT, AST, ALP,
direct-bilirubin, and cholesterol that may be attributed to In addition, chamomile flower and fennel seed extract
the liver injury and also confirmed by pathological changes could also significantly decrease serum ALT, AST, and ALP,
in the liver of AZA-treated rats. The increase of serum ALT, suggesting their hepatoprotective activity. The mechanisms
AST, and ALP activities may be mainly due to the leakage of by which chamomile flower and fennel seed extracts offered
these enzymes from the liver cytosol into the blood. In their protective effects against AZA hepatotoxicity are based
[39]
necrosis or membrane damage, ALT and AST are released into on their antioxidant abilities, which may be responsible for
circulation, and it can, therefore, be measured in serum as protecting the hepatic cells against the oxidative stress,
markers of hepatic damage. Furthermore, our results are in possibly by increasing the endogenous defensive capacity
[40]
agreement with a study which reported the cholestatic type of the liver to combat oxidative stress induced by AZA.
of liver injury in a man treated with AZA, as developed after This in turn improves the liver integrity and function and
16 days of starting AZA therapy. [41] consequently improves the hepatic excretory function
of bilirubin and also improves lipid metabolism. This
Serum ALP and total-bilirubin levels are also related to improvement was more pronounced in the animals that were
the status and function of hepatic cells. The increase in received fennel seed extract. Chamomile flower and fennel
serum ALP is due to increased synthesis in the presence seed extracts also significantly ameliorated the decrease in
of biliary pressure. Bilirubin has been used to evaluate the BWG. This may be attributed to the antioxidant effect
[42]
chemically-induced hepatic injury. It is one of the most useful of these extracts.
clinical clues to the severity of necrosis, and its accumulation
is a measure of binding, conjugation, and excretory capacity Several reports demonstrated that chamomile flowers and
of hepatocytes. [43] fennel seeds extracts contain important nutrients and exhibit
antioxidant functions. The results of our recently published
Lipids concentration is determined by metabolic functions, study revealed that the methanolic extract of both plants
which are influenced by the integrity of vital organs such possesses considerable amounts of phenolic compounds and
as the liver and kidney. Therefore, lipid profile such as radical scavenging activity, which were in agreement with
[51]
cholesterol and triglycerides are increased in hepatopathy. those reported recently. Some phenolic compounds have
[52]
The lipid content of hepatocytes is regulated by the the capacity to quench lipid peroxidation products, prevent
integrated activities of cellular enzymes that catalyze lipid DNA oxidative damage, and scavenge ROS. [53]
uptake, synthesis, oxidation, and export. [44]
Flavonoids isolated from chamomile, such as apigenin
In the current study, the observed decrease in BWG in rats and luteolin, have been shown to possess antioxidant,
treated with AZA are in agreement with the observations anticarcinogenic, carminative, antispasmodic, and mild
which reported the weight loss in rats and mouse sedative properties. Fennel seed extract contains, by
[46]
[45]
[54]
exposed to cytotoxic agents such as AZA and methotrexate chromatographic analysis, trans-anethole, fenchone,
which could possibly be due to the inhibition of DNA methylchavicol, limonene, α-pinene, camphene, ß-pinene,
synthesis and increased oxidative stress with consequent ßmyrcene, α-phellandrene, 3-carene, camphor, and
cellular damage of the body organs in affected rats. [45] cisanethole. Among these, dlimonene and ß-myrcene have
[55]
been shown to affect the liver function. D-limonene increases
Since oxidative stress has been recognized to be involved the concentration of reduced GSH in the liver. [56]
in etiology of several liver diseases and because liver is
very susceptible to toxic effects, natural antioxidants, and The biochemical investigations were confirmed by the
plant extracts have been proposed as therapeutic agents to histopathological results of the liver tissue. In our study,
protect against liver damage. Administration of chamomile light microscopic examination of AZA-treated rats revealed
[47]
flowers and fennel seeds extracts to AZA-treated animals was hepatocytes disorganization, fatty degeneration indicated
potentially effective in reducing the lipid peroxidation and by large and microvesicular fat droplets and shrinkage,

132 Hepatoma Research | Volume 1 | Issue 3 | October 15, 2015