الفهرس 
Introduction and aim of the workOnly 14 pages are availabe for public view
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Abstract
In this work the combined effect of reduced glutathione, .cYstein. beta carotene and sodium selenite on the toxicity of AFB1 was investigated in male albino rats.
It has been observed that this chemical substances inhibited the appearance of clinical signs characteristic for AFB1 and the mortality among these rats, whether they were used in a proflactic or treatmental dose. These fact was based upon the observation that in the two groups of rats administered AFB1 and treated with these subsances or given proflactic dose and treated with the chemical substances no clinical signs or mortality were observed. However, in the group of rats administered AFB1 only mortality of 16% was observed.
Autoradiographic studies using labelled thymidine revealed that the combined effect of the above mentioned chemical substances when used as treatment or proflexis could inhibit the binding effect of AFB1 and it’s metabolites to the DNA of the hepatic, kupffer and biliary epithelium.
This fact was based upon the observation that statistical analysis of the data obtained from autoradiography indicated that the percentage of labelled cells and the number of granules over labelled
cells in rats administered AFB1 only was highly significantly decreased when compared to those of the normal control rats, in the same time these two parameter in the group of rats administered AFB1 and treated or given proflactic dose of the chemotheraputic agents showed no significant changes. Inhibition of the binding of AFB1 to DNA of liver cells play a significant role in the prevention of hepatic cell damage and a series of preneoplastic changes essential for the process of carcinogenesis.
Autoradiographic studies using labelled thymidine also indicated that the use of chemotheraputic agents alone have no effect on the activity of DNA in the hepatocytes, kupffer cell and biliary epithelium i.e. no significant changes observed between the group of rats administered chemotheraputic agents only and the normal control group.
The use of coichicine to study the mitotic activity in the hepatocytes, kupffer cells and biliary epithelium in rats administered AFB1 indicated that the combined effect of the usable chemotheraputic agents inhibited the mitotic activity in the hepatocytes, kupffer cells and biliary epithelium due to repairative regeneration and proliferation of these cells. This fact was based on the observation that the mitotic index in the group of rats administered AFB1 only was highly significantly increased when compared with those of the normal control group. At the same time, the mitotic index of rats administered AFB1 and treated or given proflactic dose of the chemotheraputic agents did not differ significantly when compared to the normal control group.
The combined effect of the used chemotheraputic agents has a prominant inhibitory effect on the changes in the concentration of total serum bilirubin, total serum protein, albumin, globulin, albumin / globulin ratio and on the activity of SOOT and SOPT. These facts were evident from statistical analysis of these parameters in the group of rat administered AFB1 only and group of rat administered AFB1 and treated or given proflactic dose of the chemotberaputic agents. The total protein and albumin concentration were highly significantly decreased in rat administered AFB1 only, however remain unchanged in rats administered AFB1 and treated with the chemotheraputic agents.
Serum globulin concentration was nih in the serum of rats injected with AFB1 only. This indicated the immunesuppresive effect of AFB1. At the same time, we must point to the fact that serum globulin concentration in the serum of rat treated with the chemotheraputic agents was not significantly changed i.e. the usable chemotheraputic agent inhibited the immune suppresive effect of the
AFB1.
The concentrations of serum enzymes SOOT and SGPT were highly significantly increased in the group of rats administered AFB1 alone. This two enzymes owed it’s origin to the hepatic cells damage. The fact that these two enzymes were not significantly changed in rat treated or given proflactic dose of chemotheraputic agents indicated the inhibitory effect of these agents to the action of AFB1 on hepatocytes either functionally or morphologically.
Highly significant increase in total bilirubin concentration in the serum of rats administed AFB1 was observed. As, this parameter was not significantly changed in rats treated with the chemotheraputic agents pointed to the fact that the chemotheraputic agents inhibited the functional and morphological damage of the hepatic cells.
Pathological investigation revealed that changes were observed only in the rats administered aflatoxin only and killed at different times of experimental period. These changes were represented by acute toxic hepatitis which was observed in rats died during the early stage of the experiment or in rats killed after one and two weeks post experimental period. Also chronic regenerative and hyperplastic changes were observed in rats killed after three, four, five weeks and three months of the experimental period. The chronic regenerative process was manifested by an extensive cell turnover of the hepatocytes with increased number of cell showing mitosis and binucleate cells. While chronic hyperplastic changes were evident by fibroplasia, proliferation of the biliary epithelium and undifferentiated cells.
Although in this work neoplasia did not develop. Evidences of it were prominantly observed in all group of rat administered AFB1 only. These evidences of neoplasia represented by severe extensive fibroplasia, hyperplasia of the biliary epithelium, higher mitotic index, proliferation of undifferentiated cells and prominant regenerative changes of the bepatic cells.
In rats administered AFB1 alone and killed after three months evidences of recovary and compansation of hepatic cell function were observed (serum biochemical changes). However, the chronic reactive pathological processes still predominating.
All these pathological changes were not observed in the rats administered aflatoxin and chemotheraputic agents. So we can emphysize that the administered chemotheraputic agents inhibited a series of chronic pathological processes which might play a significant role in mechanism of carcinogenesis.
In conclusion our results demonstrated that reduced glutathione, cystein, sodium selenite in drinking water and beta carotene in food significantly inhibit AFB1 binding DNA in rats liver. Such an inhibition was probabely responsible for prevention of hepatic cell damage. Therefore, it prevented clinical signs, mortality and serum biochemical changes resulted from the action of AFB]. inhibition of the binding effect of AFB1 to DNA also played a significant role in the protection of the hepatic cells against a series of serious chronic preneoplastic changes essential for the process of carcinogenesis.