الفهرس 
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Abstract
The plant growth regulator gibberellic acid (GA3) is widely used in agriculture in many countries. However, little is known about its danger to human and animal health or its physiologic and biochemical pathways. The world’s human population is exposed to GA3 and other PGRs daily through the consumption of food products containing these chemicals.
GA3 is highly persistent and bioactive in soil for months. Since, it is easily absorbed dermally, orally or by inhalation. GA3 can induce toxicity, it affects badly in antioxidant system and cause oxidative stress, leading to the production of free radicals and cell apoptosis in many organs, including liver.
Antioxidants may protect cells by variety of mechanisms, including the conversion of ROS to non-radical species (which are dependent on the antioxidant involved), breaking the auto-oxidative chain reaction initiated by ROS and decreasing localized oxygen concentrations. The intake of exogenous antioxidants may support the antioxidative defense.
Natural compounds derived from marine organisms exhibit a wide variety of biological activities. D. dichotoma is one class of brown algae that is known to harbor a wide variety of biologically active materials which hold much medicinal potential. Many potent antioxidants have been identified and isolated from D. dichotoma, including carotenoid pigments, phlorotanins, sterols, sulphated polysaccharides, and catechins. Thus, their use as a protective agent against oxidative stress induced damage cause by Gibberellic acid would have high potential.
Few researches have been conducted to study molecular basis of cellular damage of gibberellic acid in adult rats exposed to GA3, plus fewer reports are investigating the protective effect of antioxidant-rich brown algae D. dichotoma for mitigation of these effects. In our study, we are going to evaluate the toxic effect of sub-chronic exposure to gibberellic acid on liver cells, including molecular and subcellular degenerative changes. Then the alleviating potential of brown algae on the oxidative stress induced on these cells.
In the present study, Five equal groups of adult male albino rats with total of 50 rats will be recruited for the experiment; one (negative control) received distilled water, while the second group was treated with 3.85 mg/kg body weight of GA3. Third group were administere 100 mg/kg/day of D.dichotoma extracts loaded on 1% carboxymethylcellulose (CMC). The fourth group was administered 3.85 mg/kg body weight of GA3 and 100 mg/kg of D. dichotoma extracts simultaneously. The last group received 1ml of 1% CMC by oral gavage, five days per week for a total of fifty days.
The results indicated that GA3 induced a significant increase in liver function parameters based on serum ALP, ALT, AST, and albumin, which indicate hepatotoxicity. D. dichotoma extract treatment exhibited a marked improvement in LFTs levels compared with the GA3-treated group.
group treated with GA3 showed a significant increase in malondialdehyde (MDA) levels and a marked decrease in GSH, GST, and SOD were observed as a result of induction of lipid peroxidation and oxidative stress. In contrast, administration of D. dichotoma extract to GA3 administered rats potentially increased the declined GSH, GST, and SOD level and decrease MDA level.
Histopathology examination of liver tissue of the group administrated GA3 revealed severely degenerated hepatocytes including cytoplasmic vacuolations and cellular apoptosis with nuclear condensation. D. dichotoma extract treatment improves these abnormal histopathological changes through restoring the typical structure of most damaged hepatocytes.
Bcl2, showed a significant reduction in hepatic tissue of the GA3-treated group This decreased Bcl2 immunoreactivity may be explained by the ability of gibberellic acid to induce apoptosis. Also, there was a significant up-regulation of gene and protein expression levels for the pro-apoptotic markers, Caspase-3 and Bax, In contrast, the group that co-administered GA3 with brown algae D. dichotoma showed strong Bcl2 immunoreaction and down-regulation of gene and protein expression levels for Caspase-3 and Bax.
GA3 treatment caused increase in inflammatory marker levels, TNF-α and IL6 as well as CRP. Administration of D. dichotoma extract to GA3 treated rats restores this disturbance by reducing the inflammatory marker levels, TNF-α and IL6 as well as CRP.