The Electrical Conductivity of Bone Marrow Cells Suspension Associated with Proliferative Activity and Depends on the Donor's Age and the Functional Activity of the Liver.

Copper ions play various roles in mammalian cells. Some investigations indicated that copper correlates with liver fibrosis and changes in bone marrow cells. Here, we explored the role of bone marrow cell parameters in copper liver fibrosis development and possible underlying mechanisms. The age-related features of biochemical indicators, bone marrow cell parameters, and electrical conductivity of 3- and 20-month-old male Wistar rats treated with copper II sulfate pentahydrate (CuSO4 × 5H2O) have been investigated. Based on the obtained earlier experimentally data in our laboratory, dose of 1 mg/100 g (0.58 mg/g of liver) was used. Induced liver fibrosis caused a change in the number and ratio of morphotypes of bone marrow cells, calcium and copper content, redox-system activity. These parameters depended of animals' age and presence of liver fibrosis. We also demonstrated that electrical conductivity can be used as integral parameter. In conclusion, the "adaptive response" modifies the emerging reactions of the organism to new external factors.

[Liver-induced fibrosis in young and old animals is accompanied by age-dependent changes in bone marrow cells.]

The hypothesis of dependence of the functional characterizations of bone marrow cells (BMC) - proliferation rate, direction proliferation, etc. - not only by the age of animals, but also on features of BMC microenvironment was verified. Two methods of changing the microenvironment were used. There were in vivo (induction of liver fibrosis in young and old animals) and in vitro (transfer of young and old animals BMC obtained in intact animals and animals with fibrosis into the same standard culture system). CuSO4-induced liver fibrosis and CCl4-induced liver fibrosis had a different effect on the ratio of cell types in the bone marrow in young and old animals. Thus, in young animals, regardless of the type of liver fibrosis inducer, the relative number of morphologically identifiable cell types decreased. This was accompanied by an increase in the number of identified cell types against the background of CuSO4-induced liver fibrosis and did not change against the background of CCl4-induced liver fibrosis in old animals. The proliferative activity of BMC isolated from old animals and transferred to an in vitro culture was superior to that of young animals. This is due to the large number of lymphocytes in the bone marrow of old animals by 167% and the specific composition and characteristics of the BMC microenvironment in old animals.

[Donor age affects on the «behavior¼ and the sensibility bone marrow cells in on copper ion of the primary culture].

The changes of bone marrow cells (BMC) number in the primary culture from 0 to 96 hours, the pattern (the distribution of cells) of cells morphotypes and «lifespan¼ (the time of cell life after isolation) of myelocytes, metamyelocytes, band and segmented neutrophils, isolated of the young (3 months) and old (20months) animals, were investigated. The number of the BMC obtained from intact old animals increased faster in primary culture, than from young animals. The Cu induced fibrosis had different influence on the rate of BMC culture growth of old and young animals. The adding of 4 mM and 8 mM CuSO4x5H2O in the BMC culture of young and old animals resulted in a dose-dependent inhibition of growth rate of young animal cells. If copper ions were added into the culture of BMC of old animals, the decreased of the BMC number was described less than for cells of young animals. The adding of 8 mM CuSO4x5H2O inhibited proliferation less, than the adding of 4 mM CuSO4x5H2O. The Cu-induced liver fibrosis had accelerated the BMC rate death of both old and young animals. However, this effect was more pronounced in young animals. It is suggested, that during the ontogenesis the BMC undergo such epigenetic changes, which change functional properties.