الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
The liver is the critical organ in the body. Liver is the main detoxifying and metabolic organ in the body. It removes poisons from the body, and performs the metabolic functions.
Carbon tetrachloride (CCL4) is an organic compound safe at low concentration, but exposure to higher concentration of it can degenerate body organs and it becomes fatal in case of prolonged exposure.
The pomegranate (PO) is a red purple fruit has two parts, an outer part is hard pericarp and inner part is spongy mesocarp and the seeds attached in the inner part.
The production and consumption of PO have always been increasing due to their nutritional value. During PO processing, a large number of by-products are produced, such as peels and seeds, which can lead to environmental pollution problems. PO peel (PP) is rich in multiple bioactive compounds.
Hence our study was aimed to evaluate the efficacy of PP ethanolic extract (PPE) against the toxic effect of CCL4 on the liver in experimental male rats. Also, we aimed to compare the effect of N-acetyl cysteine (NAC) as a reference drug with PPE.
In our study PPE was performed where the PO was peeled. The peels were dried and grinded to be extracted by 70% ethanol then the extract was evaporated and lyophilized to obtain its powder form.
After that, 45 adult male albino rats aging 8-10 weeks, weighing 110-150 g were used. Rats were housed into cages for 2 weeks before beginning the experiment with a 12-hour day-night cycle, temperature of (22 ± 2.0oC) and humidity of (45- 46%). The rats were fed with a balanced commercial diet and the drinking H2O was provided adlibtum. The experiment continued for 30 days. PP was dissolved in water. CCL4 was used as a hepatotoxic agent and dissolved in olive oil (OL) with ration 1:3 respectively to be administered to the experimental rats. Rats were divided into 8 groups the first group, control, rats in this group were healthy and free from any diseases and they were only administered 1 ml dH2O orally. The second group was control OL, the vehicle of CCL4, and they were orally administered 0.5 ml of OL. The third group, control PPE, and the rats were orally administered 400 mg/kg Bwt PPE. The fourth group, control NAC, and they were orally administered 150 mg/Kg Bwt NAC. The fifth group was represented the control induction group where the rats were orally administered 0.5 ml/kg Bwt CCL4 dissolved in OL twice a week. The sixth group was the protective group with PPE and the rats in this group was orally administered 400 mg/kg Bwt PPE daily for one month and also, they were orally administrated 0.5 ml/kg Bwt CCL4 twice a week. The seventh group was protective group with NAC where the rats were orally administered 150 mg/kg Bwt NAC daily for one month with 0.5 ml/kg Bwt CCL4 twice a week. The eighth group was protective group with OL and rats were administered 1 ml OL/kg Bwt daily for one month with 0.5 ml/kg Bwt twice a week.
After 30 days, rats were fasted for 8 hours, anesthetized using isoflurane. Blood samples were collected from eye-canthus in Wisterman tubes then serum was separated through centrifugation to be used in biochemical assays. Liver was rapidly isolated from the rats and washed with cold normal saline. Each liver was divided into 3 parts, one part was preserved in 10% formalin for histological study, the second and the third parts were preserved at -20oC to be used for biochemical assays and determination of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (Il-6) at protein level.
The results exhibited that, in hepatotoxic induced group by CCL4, there was reduction in the body weight (Bwt), elevation of lipid profiles and liver enzymes activities. Also, higher concentration of oxidative stress parameters and inflammatory markers and lower level of reduced glutathione (GSH) was noticed in CCL4 group. The histopathological results of hepatic tissue revealed severe necrotic changes.
Using of PPE as a protective against hepatotoxic effect of CCL4 exposed significant restoration of Bwt, lipid profiles and liver enzymes activities. In addition, the thiobarbituric acid reactive substances and nitric oxide levels were decreased and GSH was elevated. Further, tumor necrosis factor-alpha and interleukin-6 were downregulated. Hepatic tissue of protected rats with PPE showed noticed reduction of necrosis.
On the same hand, there was marked improvement in the altered studied parameters due to toxic effect of CCL4 in both NAC and OL protected rat groups.
Conclusion
Pomegranate peel extract (PPE) has antihyperlipidemic, antioxidative and anti-inflammatory effect on hepatic tissue affected by side effect of carbon tetrachloride, but it is recommended to further studies explain the mechanism of action, pharmacological effect, side effect and toxicity of PPE on various body organs to prove is it safe or not to be used?