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Hassan et al.                                                                                                                                Potential antioxidant activity of cape gooseberry against HCC

           aminotransferase activity is more specific for liver   of H 2 O 2 , which is an effective inhibitor of SOD. [50,51]  The
           injury due to damage to the liver cell membrane. [40]    reduction in the activity of CAT may reflect the inability
           As well, alkaline phosphatase is used as a specific   of tissues to eliminate H 2 O 2 . CAT protects SOD
           tumor marker for making diagnoses in the early     against inactivation by H 2 O 2 , while SOD protects CAT
                                                                                    2-
           detection of cancer. [41]  This enzyme is involved in the   against inhibition by (O ). Thus, the balance of this
           transport of metabolites across cell membranes, in   enzyme system may be essential to eliminating ROS
           protein synthesis, secretory activities and glycogen   generated in the tissues. In this area, GSH represents
           metabolism. It is a membrane-bound enzyme,         an important defense mechanism in protecting cells
           and its alteration is likely to affect the membrane   against ROS. [52]  On the other hand, the enormous
           permeability that produces derangement in the transport   impacts of CGJ supplementation in alleviating
                       [42]
           of metabolites.                                    oxidative stress in all organs in the HHC rats may be
                                                              attributed to either a direct effect of many antioxidant
           The observed increases of serum and liver ALP in HCC   compounds of CGJ as free radical scavengers, or to
           rat groups may be due to altered gene expression. [43]    enhancement of cellular antioxidant defense functions.
           In the current study, the HCC rats group suffered from   This occurs through modulating the alteration in
           severe oxidative stress in various organs, achieved   GSH content and antioxidant enzymes activity. An
           by elevation of MDA level and depletion of antioxidant   amelioration of AFP after supplementation of CGJ
           enzymes. This may be due to the conversion of      to HCC rats may be due to the antioxidant activity of
           cellular poly-unsaturated fatty acids to the toxic product   CGJ. Additionally, the observed increase in alterations
           MDA which has a cytotoxicity and inhibitory action   to liver enzymes, including ALT, AST and ALP, in HCC-
           on cellular protective enzymes. [44]  HCC caused by   received CHJ rats may be due to the improvement of
           carcinogenic DENA generally reflects instability of   the functional status of hepatocytes with preservation
           liver metabolism associated with free radicals species   of cellular architecture leakage of intracellular enzymes
           (ROS) generation, which leads to oxidative stress and   through membrane-stabilizing activity. [18,53]
           alterations in antioxidant defense mechanisms. [35,45]
           Increased level of MDA has been reported during    Previous studies have suggested that CGJ is a
           DENA-induced hepatocarcinogenesis. This dynamic                                                  [54]
           action may further lead to uncompromised production   significant source of natural antioxidative compounds.
           of free radicals overwhelming the cellular antioxidant   These  components  may have  a wide  variety of
           defense. [46,47]  Moreover, HCC causes depletion of   chemical structures that could react with radicals by
           SOD and CAT activity as well as TAC and GSH        donating protons (free radical quenching), radical
           contents in all observed organs. Such studies      addition, redox reaction (electron transfer) and radical
                                                                          [12]
           support the current findings, as the current study   combination.   Natural antioxidants could prevent
           showed a significant decrease in the activities of   the deleterious effects of toxic agents by scavenging
           antioxidant enzyme in the liver of animals treated with   free radicals and other ROS or by modulation of the
           carcinogen. [35]  Antioxidants are substances that either   inflammatory response. The supplementation of CGJ
           directly or indirectly protect cells against adverse   to the HCC rats model resulted in amelioration of
           effects of xenobiotics, drugs, carcinogens and toxic   oxidative stress. The improvement of the antioxidants
           radical reactions. [48]  The observed decrease in SOD   defense mechanism is considered a favorable indicator
           activity in liver, kidney, brain and testes suggests the   for anti-lipid peroxidative properties and antioxidant
           inactivation of antioxidant enzymes; this is possibly   activity through high levels of antioxidant compounds
           due to increased superoxide radical production or   such as polyphenols and similar flavonoids. [55,56]
           to an inhibition by H 2 O 2  as a result of corresponding
           decrease in the activity of catalase which selectively   The observed decreases in MDA in HCC rats that
           degrades H 2 O 2 . [49]  The decreased GSH, SOD and   received CGJ may be due to free radicals scavenging,
           CAT observed in the HCC group of rats may be due   a potential mechanism by which CHJ can act as an
           to accumulation of lipid peroxidation that was seen to   anti-inflammatory and antioxidant to protect the liver
           increase during carcinogenesis.                    and other organs. Therefore, dietary consumption of
                                                              cape gooseberry may be a highly effective potential
           The accompanying reduction in the activity of SOD,   antioxidant and protective agent against oxidative
           CAT and depletion of GSH content suggests induction   stress in liver toxicity. [57,58]
           of oxidative stress in the organs studied. SOD is
           considered the first line of defense against deleterious   In view of the present results, it was observed that
           effects of oxygen free radicals in the cells by catalyzing   CGJ supplementation showed a significant antioxidant
           of superoxide radicals (O ) to H 2 O 2  and molecular   status as manifested by elevation of GSH, TAC, SOD
                                   2-
           oxygen. CAT is also responsible for the detoxification   and CAT in serum and various organs. Many plant
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