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INTRODUCTION                                        acyl-derivatives. Other principal components are essential oils
                                                              such as terpenoids, α-bisabolol and its oxides, and azulenes
          Hepatotoxicants, including viruses, fungal products, bacterial   including chalmuzene and acetylene derivatives. [13]
          metabolites, minerals, environmental pollutants, and
          chemotherapeutic agents, can induce various disorders of the   Fennel (Foeniculum vulgare Mill.), a plant belonging to the family
               [1]
          organ.  Azathioprine (AZA) is a common immunosuppressant   Apiaceae, has a long history of herbal uses. Fennel seeds are
                                                  [2]
          drug used in medicine to treat different diseases.  It is now   used as analgesic, carminative, anti-inflammatory, diuretic,
                                                                                    [14]
          widely used in oncology, dermatology, gastroenterology, and   and antispasmodic agents.  The antioxidant potential and
          rheumatology for its anti-leukemic and immunosuppressive   antimicrobial activity of fennel seed extracts and essential
                     [3]
          properties.  AZA (6-(1-methyl-4-nitroimidazol-5-yl)   oil have been reported. [14,15]  Fennel seeds methanolic extract
          thiopurine) is also used for the prevention of rejection   contains (FSMEs) high amount of polyphenols, including
          in organ transplants and the treatment of auto-immune   flavonoids as a major component of polyphenols, gallic
                 [4]
          diseases.  It is indicated as an adjunct for the prevention of   acid, caffeic acid, ellagic acid, quercetin, and kaempferol.
                                                                                                             [16]
          rejection in the renal transplantations. AZA is also used in   Trans-anethole, fenchone, estragole, 4-terpineol, sabinene,
          the prevention of rejection in cardiac, hepatic, and pancreatic   alpha-terpinene and monoterpene hydrocarbons (limonene)
          transplantations. [5,6]                             as the major compounds, were identified in the essential oil. [17]

          The therapeutic use of AZA is associated with many   The present study was undertaken to elucidate the ability of
          complications. It induces a range of toxic effects that   oral chamomile flowers methanolic extract (CFME) and FSME
          may ultimately result in the discontinuation of treatment.   to alleviate the adverse effects of AZA on the liver through
          These toxic effects include gastrointestinal disturbances,   biochemical and histological examinations in albino rats.
          pancreatitis, reversible alopecia, rashes, fever, tachycardia,
                                                    [7]
          pneumonitis, hypotension, and renal dysfunction.  Many   METHODS
          studies have frequently reported the hepatotoxicity of
          AZA in vitro and in vivo. Many of these studies related the   Experimental animals
          mechanism of hepatotoxicity and liver injury to the oxidative   Male albino rats (Sprague-Dawley strains) weighing
          stress. AZA toxicity to rat hepatocytes in vitro and the   150-200 g were used in this study. They were obtained from
          mechanism of AZA toxicity to hepatocytes and decreasing   the animal house of National Research Centre, Giza, Egypt
          its viability involves the depletion of glutathione (GSH)   and acclimatized for 1 week prior to the experiment. Animals
          leading to mitochondrial injury with profound depletion   were housed in stainless steel cages at room temperature
          of adenosine triphosphate (ATP) and cell death by necrosis   (20-25 °C) and a photoperiod of 12 h light-dark cycle. Animals
          were reported. [8,9]                                were allowed free standard laboratory diet and drinking tap
                                                              water ad libitum.  This experimental study was approved by
          Plants rich in natural polyphenolic compounds were   review board of National Research Centre.
          intensely studied in recent years due to their potent   Chemicals
          anticarcinogenic, antioxidant, and immunomodulatory   AZA B.P uncoated tablets 50 mg manufactured by RPG Life
          properties. Chamomile (Matricaria recutita L.) is one of the   Sciences Ltd., Ceat Mahal, 463, Dr. A B Road, Worli, Mumbai:
          most widely used medicinal plants in the world. Aqueous   400 025, India. Methyl alcohol (98%) was obtained from
          chamomile extract is used as herbal medicine, in the form   El-Nasr Pharmaceutical Chemicals Co., “ADWIC” (Egypt).
          of tea, demonstrated to possess anti-inflammatory and   Perchloric acid and trichloroacetic acid (extra pure 99%)
          antioxidant properties. [10]  Chamomile preparations are   were manufactured by SISCO Research Laboratories PVT
          commonly used for many human ailments such as hay fever,   LTD (Mumbai, India). Thiobarbituric acid was purchased from
          muscle spasms, menstrual disorders, insomnia, ulcers,   MERCK (Darmstadt, Germany). Other solvents and chemicals
          wounds, gastrointestinal disorders, rheumatic pain, and   used were either analar or of analytical grade unless otherwise
                     [11]
          hemorrhoids,  and also used to treat anxiety, hysteria,   specified. Plant materials: Dried chamomile (Matricaria
                                                     [12]
          nightmares, insomnia, and other sleep problems.  The   chamomilla) flowers and dried fennel (F. vulgare) seeds were
          useful effects of chamomile are related to the presence   purchased from Abd El-Rahman Harraz (Bab El-Khalk Zone,
          of several flavonoid constituents (the most abundant   Cairo, Egypt).
          phenolic compounds in herbs), and the core structure
          consists of either flavone (apigenin and luteolin) or flavonol   Preparation and extraction of the plant materials
          derivatives (quercetin and patuletin). These occur in various   Three samples of dried chamomile flowers and fennel seeds
          forms such as aglyco- mono- and di-glycosides and/or   were ground. Eighty grams of each ground sample were

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