الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
One frequently used food preservative is sodium benzoate (SB). that has been approved by regulatory agencies such as the FDA and is generally regarded as safe (GRAS) and approved by EFSA.. In spite of the the regulatory bodies’ assurance that SB is secure in human, its utilization has persisted controversial, and there have been reports that excessive intake of SB could have adverse effects .Therefore, the present study aimed to explore the possible dose-dependent cardiac adverse effects of SB in male rats. Also, the study investigated the changes in the expression of multiple components in the cardiac redox and autophagy pathway, including Beclin-1, LC3, ULK1, and Atg7, in order to assess the potential associations between exposure to SB and the change in the cardiac autophagy.
Our study was carried out on fourty albino male rats which were separated into two several teams: one served as control, group two was treated with sodium benzoate and divided into seven sub groups: group one was treated with at 1 group two, mg/Kg BW was handled with 10 g/Kg BW of, group three was handled with 50 mg/Kg BW, group four was administered 100 mg/kg BW, group five was handled with 250 g/Kg BW of SB, group six was treated with 500 g BW and group and mg seven had been given 1000 mg/Kg BW. Animals were treated orally with respective dose every day for 90 days. As a result of the experimental periods, every rat will be anaesthetized and sacrificed. blood was drawn for testing. the assessment of the following: AST, LDH, CK-MB, and troponin-I, (NOx), (MD,A, 8-OHdG, TNF-α and caspase3, heart tissues was dissected out for determination of autophagic gene expression of the following parameters: Beclin-1, LC3, U,LK1 and Atg7.
The results indicated that, the serum markers of cardiac functions; AST, LDH, CK-MB, and troponin-I showed no significant changes in the rats long-term (90 days) treated with increasing doses of SB ranging from 1-250 mg/Kg, while the rats treated with the higher doses (500 and 1000 mg/Kg) revealed substantial increases compared to the baseline rats and rats treated with lower doses. The changes in serum cardiac parameters upon treatments with increasing doses of SB are associated with disturbed redox balance in the cardiac tissues. The glutathione system showed marked shifting from the reduced stat into more oxidizing stat in the rats treated with SB the dosage of 100mg/Kg and higher in a manner dependent on dose as indicated by decreasing quantities of total and reduced GSH and expanding levels of GSSG and resultant decline in the redox ration (GSH/GSSG). The impairment of cardiac GSH redox system a combined with marked elevation of nitric oxide end product (NOx) and MDA at the highest doses used (500 and 1000 mg/Kg), and marked elevation of 8-OHdG at much lower doses of SB (100 mg/Kg and higher). The induction of oxidative stress in the cardiac tissues by SB was associated with induction of inflammation as indicated by significant dose-dependent increase in the cardiac level of TNF-α starting from the dose of 50mg/Kg. The current study clearly indicated a dose-dependent activation of caspase-3 activity in the cardiac tissues by SB starting from the dose of 100mg/Kg and higher. The SB caused dose-dependent induction of the cardiac expression of autophagic genes; becline-1, LC3, and ULK1 starting from the doe of 50 mg/Kg and thereafter in dose-dependent fashion. The expression of cardiac ATG7 upon exposure to different doses of SB showed biphasic changes as its expression is suppressed with the lower doses (50 and 100 mg/kg) while it markedly induced with the higher doses of SB (250-1000 mg/kg), the significance of these biphasic changes needs further investigations. All of these data may indicate that SB at high doses markedly induce the cardiac autophagy.
Summary and Conclusion
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from the previous discussion, we can conclude that
1.
Sodium benzoate is a compound with a broad safety profile and dose-dependent detrimental effects on the cardiac system in the case of low doses (50 mg/Kg and higher).
2.
The mechanism of these effects may include redox imbalance, induced oxidative stress showed by significant decline in the redox ratio (GSH/GSSG), and combined with marked elevation of NOx, MDA and 8-OHdG.
3.
Also, SB induce inflammation and apoptosis in cardiac tissues showed by marked increase in TNF- α and caspase-3 activity.
4.
SB caused dose-dependent induction of the cardiac expression of autophagic genes; becline-1, LC3, and ULK1 starting from the doe of 50 mg/Kg and thereafter in dose-dependent fashion.
5.
However, the description of SB as a safe additive, but due to the fact that it is commonly present in food, beverages, and plants (like cinnamon) the total dose taken by populations cannot be completely counted and controlled, and therefore, many of people may be subjected daily to high doses of SB but they are unaware.
6.
So, finding the right dose with the least possible side effects need further research.