The effect of iron overload on hematopoietic system, bone marow and related genes in rats

Most of research has been done about structure of the proteins and genes responsible for metamorphosis process of erythrocytes in the bone marrow, absorption of iron in the intestines, transportation to the cells, its usage and storage. Most of this research was done in ineffective eritropoezis. In the conditions which eritropoezis continue normally, it wasn?t entirely discovered what the systematic effects of external iron supplement on hematopoietic organs are. The aim of this research is to find out the information about iron overload on normal eritropoiesis. The target genes are in the bone marrow, peripheral circulation, liver tissue and they get effected by iron in the body. In our research, the goal is defining the expressional changes in these target genes caused by iron supplementation. The results of research is considered to be usable for prognosis and treatment in iron overload disease.In our research, Wistar-Albino type, 12-16 weeks-old, 20 male rats were used. They were separated into two groups: The group that is supplemented with iron (n=10) and the control group (n=10). The rats in the test group has been given 100 mg/ kg by intraperitoneally iron dekstran 3 days a week for 2 weeks. Control group is given 5 ml SF. After 1 mounth, rats were sacrificed and peripheral blood samples were collected. The samples were examined for hemogram and biochemical parameters. On the other hand, the samples of the bone marrow were examined for changes in eritropoietic precursors using flow cytometri, and for gene expression analysis using PCR technique. Gene expression analysises were done through PCR technique in the liver tissue to determine the changes iron related gene expression.Although results of iron and ferritin rates in serum were found to increase explicitly (p= 0.0001), there wasn?t any difference in the eritroid paremetres like hemoglobin and hematocrit (p>0.05). But RDW rates were determined to raise significantly (p= 0.001). Analysis of the bone marrow using the flow cytometri showed that the percentage of CD71 (+) cells in the total eritroid cells didn?t change for the iron overload rats (p>0.05). However, CD71 expression and cell sizes were observed to increase in the CD71 low (+) cells (p<0.05). In bone marrow, increase in EpoR gene expression (p=0.007) ,decrease in TfR1 gene expression (p=0.003) and increase in TfR2 gene expression (p=0.001) were observed. In liver tissue gene expressions, in addition to TfR1, TfR2 and HFE gene expressions were also seen to decrease significantly (p<0.05). Hepsidin gene expressions weren?t observed to change significantly in the other analysises of liver tissue (p>0.05)In our research, eritroid paremetres were not seen to be changed despite the iron overload. Expression changes were observed in erytropoietic cells in bone marrow for decreasing the entry of iron. Late period of cell percentage of bone marrow decreased due to compensate the iron increase in the peripheral eritroid indexes. On the contrary, the early period eritroid cell percentage increased. Mechnanisms that will decrease hepsidin synthesis in hepatocites started to be stimulated as a response to systematic iron accumulation in the rats that are examined in the subacute period after the iron accumulation.In conclusion, erytroid paremetres in peripheral and bone marrow of the iron overload rats were not changed and hepatic response to decrease iron load in organism is created. In the future, designating these changes after iron overload in the eritropoezis and liver with time- course study, will be important for diagnosis and treatment of the diseases characterized by iron accumulation.