Abstract

EFFECT OF PERINATAL ADMINISTRATION OF DIFFERENT FORMS OF VITAMIN D3 ON ORGANS CONTRIBUTING TO THE HORMONE METABOLISM IN BALB/C MICE POSTNATAL PERSISTENCE OF HEPATIC HEMATOPOIESIS

Doaa S. Mansour, Yakout A. El-Senosi, Mohsen I. Mohamed* Mahmoud A. Elaroussi and Magda M. Amer

ABSTRACT

The present study was conducted to assess the effect of administration of different forms of vitamin D3 in pregnant BALB/c mice on the growth and hepato-renal performance of their offspring. Four equal groups of two weeks pregnant BALB/c mice each of ten have been utilized in the present work. One control group was injected with 100 μl propylene glycol (G1) while the other was injected with 20 ng cholecalciferol in 100 μl propylene glycol (G2), 20 ng 1,25dihydroxy vitamin D3 in 100 μl propylene glycol (G3), or 50 ng 1-alpha hydroxy vitamin D3 in 100 μl propylene glycol (G4) intrapertoneally, respectively every other day until the delivery time. Six weeks old offspring were sacrificed and blood samples were taken for theDetermination of CBC, serum alanine transaminase (ALT) and aspartate transaminase (AST) and alkaline phosphatase (ALK) activities Serum creatinine and urea levels were also monitored. Livers and kidneys were excised for histopathological examination. Data from the present study showed that perinatal administration of all vitamin D3 compounds caused variable degree of bone malformation and retarded growth rate. Microscopical examination of livers of perinatally treated mice showed evidence of extramedullary hematopoiesis including the presence of immature hematopoietic cells. Colonies of nucleated red cells, myeloid cell lineage including neutrophils and eosinophil precursors together with megakaryocytes were demonstrated within the examined sections. Hematopoietic colonies were located inside the hepatic sinusoids which underwent marked dilatation. Animals also experienced hepto-renal damage manifested with necrotic changes of hepatocytes and variable degrees of glumerulo-tubular affection. The hepatic damage was associated with a significant rise of ALT in which ALT level for the control group was 28.6±5.13 and increased significantly to 49.4± 1.14 , 60.2± 4.66 and 68.0 ± 2.92 for G2,G3 and G4 , respectively, wherein also there was a similar increase in AST serum activity. The renal damage caused a significant rise in serum urea and creatinine levels. Data also showed that the utmost histopathological damage and the most profound biochemical changes were observed amongst (G4) i.e group receiving 50 ng 1- alpha hydroxy vitamin D3 All changes were associated with a progressive and a significant rise of both serum calcium and phosphorus levels of all groups. In conclusion, data from the present study address the role of perinatal exposure to high dose vitamin D3 in the persistence of postnatal liver hematopoiesis in BALB/c mice. They also herald its toxic hepato-renal effect in mice offspring. This harmful effect was associated with profound hypercalcemia and hyperphosphatemia. Our study, suggests reappraising the safety of the therapeutic potential of supra physiological doses of vitamin D3 during pregnancy on the welfare of the offspring.

Keywords: Vitamin D3, extramdullary hematopoiesis, hepato-renal toxicity.