الفهرس | Only 14 pages are availabe for public view |
Abstract Cinnamaldehyde (CNMA) is a pale-yellow liquid with a warm, sweet, spicy odor and pungent taste. It used as a food additive in low concentrations in human food. However, if the use of these compounds is extended to other applications that may require higher doses as well, the increased exposure of humans to these compounds is a matter of concern and this is the reason why their toxicological properties are becoming of greater relevance (Stammati et al.,1999). It is commercially prepared by the condensation reaction of benzaldehyde and acetaldehyde and chemically related to toxicologically more active compounds (Gowder and Halagowder, 2010). Gum Arabic (GA) is an edible, dried gummy exudate from the stems and branches of Acacia Senegal and Acacia seyal, that is rich in non-viscous soluble fiber. It is widely used in pharmaceutical and food industry as an emulsifier and stabilizer, and in some countries in the traditional treatment of patients with chronic kidney disease (Ali et al., 2013b). Vitamin E (VE) is the most important lipid-soluble antioxidant and protects cell membranes against oxidation (Kabel, 2014). It is considered to be beneficial for prevention of diseases associated with oxidative stress because of its remarkable anti-oxidative properties. (Li et al., 2015). Therefore, the present study was done to investigate the curative effect of GA and / or VE against CNMA induced toxicity in liver and kidney of rats. Summary and conclusion - 14 8 - The doses selected in the present investigation were 73.5 mg/kg body weight for CNMA, 7.5 g/kg body weight for GA and 1 g/kg body weight for VE. 60 young male Wistar albino rats weighting 70-90 g were divided into six groups ten rats each according the following regimen: - 1- Normal control group, orally received distilled water. 2- CNMA group at zero time, orally received dose 73.5 mg/kg b. wt. of CNMA dissolved in distilled water daily for 3 months. 3- CNMA group at 30 days orally administrated with a dose of CNMA 73.5 mg/kg b. wt. daily for three months followed without any treatment for another 30 days as a recovery period. 4- GA therapeutic group received oral doses of CNMA 73.5 mg/kg b. wt. daily for three months then orally administered GA at a dose 7.5 g/kg b. wt. daily for another 30 days. 5- VE therapeutic group received oral doses of CNMA 73.5 mg/kg b. wt. daily for three months then orally administered VE at a dose 1g/kg b. wt. daily for another 30 days. 6- Mixture therapeutic group received oral doses of CNMA 73.5 mg/kg b. wt. daily for three months then orally administered mixture of GA and VE at doses 7.5 g/kg b. wt. and 1g/kg b. wt. of GA and VE respectively daily for another 30 days. At the end of treatment, the animals were sacrificed, and then the mean body weight was calculated. Also, the livers and kidneys were weighted and the absolute and relative weights were calculated. The blood samples were collected and centrifuged for biochemical analysis. Then the liver and kidney specimens obtained from the control and treated rats were prepared to be examined histologically in Summary and conclusion - 14 9 - addition to estimation of oxidative stress and comet test. The results obtained from the present investigation can be summarized as follows: Body weight, absolute and relative liver and kidney weights: In the present study, the mean body weights of CNMA rats at zero time after 3 months significantly decreased as compared to the control group. A considerable improvement was observed in GA, VE and mixture groups. On the other hand, no significant differences were found in the relative weight of liver or kidney in control rats and other groups. Biochemical parameters: Liver enzyme tests: Normal rats showed more or less constant levels of serum ALT, AST and GGT during the course of the study. On the other hand, in CNMA group at zero time, a significant elevation was realized in ALT, AST and GGT levels as compared with control group. A considerable improvement was observed in GA, VE and mixture groups. Kidney function tests: Serum urea, creatinine, uric acid, sodium (Na+) and potassium (K+) levels: In CNMA group at zero time, a significant elevation in urea, creatinine and Na+ and decrease K+ levels as compared with control group. On the other hand, a considerable improvement was observed in GA, VE and mixture groups. Summary and conclusion - 15 0 - Oxidative stress parameters: Tissue glutathione (GSH) (nmol/g protein) levels: Normal rats showed more or less constant levels during the course of the study. In CNMA rats at zero time, a significant depletion in the content of tissue GSH was recorded. On the other hand, a slight improvement was observed in GA and VE groups and a marked increase occurred in tissue GSH content in the therapeutic rats by mixture of GA and VE. Superoxide dismutase (SOD)(u/g) activity: Normal rats showed more or less constant levels during the course of the study. In CNMA rats, a significant depletion in the content of tissue SOD was recorded. Whereas, some improvement was observed in SOD content in the GA therapeutic group. In VE therapeutic group, slight improvement was observed. On the other hand, marked increase occurred in tissue SOD content in the therapeutic rats by mixture of GA and VE. Tissue lipid peroxidation malondialdhyde (MDA) (nmol/g protein): The control rats designated more or less constant figures during the study period. On the other hand, in CNMA rats at zero time a significant elevation was realized in tissue MDA content as compared with the control group. A considerable improvement was observed in GA therapeutic rats in tissue MDA. Also, minimal improvement occurred in the MDA content of VE therapeutic rats. On the other hand, significant improvement occurred in the MDA content of therapeutic rats by mixture of GA and VE. Summary and conclusion - 15 1 - Histological studies: Microscopical studies of the liver Examination of liver sections of the control animals showed regular histoarchitecture of the liver parenchyma with well designated hepatocytes, sinusoids and central veins. In CNMA rats at zero time and 30 days a marked degree of deterioration of the liver tissue has been displayed. The parenchymal liver tissue had apparently lost most of their characteristic architectural organization, and the great majority of the constituent hepatocytes became detached from each other. In GA therapeutic group, the photomicrographs of liver sections showed cytoplasmic vaculation and deterioration nuclei of hepatic cells. In VE therapeutic group, degenerative changes within hepatic cells persisted, where some cells appeared binucleated and cytoplasmic vaculation in hepatocytes persisted. No Abreus alteration were observed fallowed mixed treatment with GA&VE as compared to treatment with either alone. Microscopical studies of the kidney Kidney of control group showed normal architecture pattern. CNMA rats at zero time and 30 days revealed marked histological lesions particularly in cortical portion. The Malpighian corpuscles lost their characteristic normal configuration and exhibited clear features of damage. The glomerular tufts were contracted and packed with RBCs. Summary and conclusion - 15 2 - Furthermore, the proximal (PCT) and distal convoluted tubules (DCT) revealed marked degenerative changes within their epithelial cells and necrotic changes in some areas were observed. Moreover, some renal tubules reflected severe alterations where the epithelium cells were replaced by flattened cells. Focal areas of necrosis were also noticed. In the GA group, showed vaculation in glomerular tuft and persistence of degenerative alteration in proximal and distal convoluted tubules. In the VE group, showed the Bruch border of the proximal convoluted tubules is eroded. In mixture group, revealed minimal changes in the structure of the kidney compared to normal ones. Both glomeruli and convoluted tubules gained partial near to normal features. Molecular studies: Comet % The control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong elevation was realized in comet percent as compared with the control group. A considerable improvement was observed in GA therapeutic group in comet percent. Also, minimal improvement occurred in the comet% of VE therapeutic group as compared with the control group. On the other hand, strong improvement occurred in the comet % of therapeutic rats by mixture of GA and VE. Summary and conclusion - 15 3 - Head diameter The control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong decrease was recorded in head diameter as compared with the control group. A considerable improvement was observed in GA therapeutic group. Also, minimal improvement occurred in the head diameter of VE therapeutic group as compared with the control group. On the other hand, strong improvement occurred in the head diameter of therapeutic rats by mixture of GA and VE. % DNA in head The control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong decrease was recorded in % DNA in head as compared with the control group. A considerable improvement was observed in GA therapeutic group. Also, minimal improvement occurred in % DNA in head of VE therapeutic group as compared with the control group. On the other hand, strong improvement occurred in % DNA in head of therapeutic rats by mixture of GA and VE. Tail length The control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong increase was recorded in tail length as compared with the control group. A considerable improvement was observed in GA therapeutic group in tail length. Also, minimal improvement occurred in tail length of VE therapeutic group. On the other hand, strong improvement occurred in tail length of therapeutic rats by mixture of GA and VE as compared with the control group. Summary and conclusion - 15 4 - % DNA in tail The control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong increase was recorded in % DNA in tail. A considerable improvement was observed in GA therapeutic group in % DNA in tail. Also, minimal improvement occurred in % DNA in tail of VE therapeutic group as compared with the control group. On the other hand, strong improvement occurred in % DNA in tail of therapeutic rats by mixture of GA and VE. Tail moment control rats designated more or less constant figures during the study period. On the other hand, in CNMA group a strong increase was recorded in tail moment as compared with the control group. A considerable improvement was observed in GA therapeutic group in tail moment. Also, minimal improvement occurred in tail moment of VE therapeutic group. On the other hand, strong improvement occurred in tail moment of therapeutic rats by mixture of GA and VE as compared with the control group. Conclusions: It could be stated now that CNMA as a food additive has serious noxious and deleterious impacts on the body organs, also revealed that, CNMA produced oxidative stress and this was associated with impairment in liver and kidney functions and tissue architecture particularly when used for prolonged periods of time. These impacts will be reflected in improper functioning, not only of the liver and kidney, but also of the whole body in general. Summary and conclusion - 15 5 - Also, from the present findings that the previously reported therapeutic effects of GA and VE against CNMA toxicity to liver and kidney injury could also be exhibited when they are given orally after exposure to CNMA. In view of the findings of this study, it may be concluded that GA and VE possess the ability to reverse CNMA induced liver and kidney oxidative injury as well as to regulate the metabolic activities and may be considered as therapeutic agent against CNMA induced toxic effects. In conclusion, there are numerous sources of free radicals that, in excess, may have deleterious effects on the human body. This study suggests that GA and VE have therapeutic effects on oxidative stress caused hepatic and renal injury induced by overdose of CNMA. The therapeutic effect of the mixture is more potent than those of GA or VE only |