Abstract

EFFECT OF TAMOXIFEN ON PRENATAL AND POSTNATAL DEVELOPMENT OF KIDNEY IN ALBINO RAT’S OFFSPRING

Eman Badawi Elshal*, Zakia Abdelhamid and Hassan Fathy

Abstract

Breast cancer is a major health problem worldwide and is the second cancer leading death especially for women. Tamoxifen (TAM), a non-steroidal antiestrogen, used as a chemotherapeutic and chemopreventive agent for breast cancer. The aim of this study was to investigate the teratogenic effects of tamoxifen on the developing kidney of the offspring of the Sprague Dawley rat at the 20th day of gestation (GD20) and at the postnatal 7th day (PND7) after delivery. Materials and methods: sixty adult Sprague Dawley 20 male and 40 female albino rats were used in this experiment. Forty pregnant albino rats were divided into two equal groups: group I (control) andgroup II (treated). Each group was subdivided into 2 subgroups. Each subgroup was consisted of (10 pregnant rats). In Group IB (GD20), tamoxifen was administered orally at a dose of 0.36 mg /day through orogastric tube for 19 days from the 1st day (GD1) to the 19th day (GD20) of gestation. In group IIB (PND7) treated group: Tamoxifen was administered daily at a dose of 0.36 mg tamoxifen orally through orogastric tube for 28 days from the (GD1) to (PND7) after delivery. At the end of the experiment the male offspring (GD20) and (PND7) were sacrificed. The kidney of both control and treated groups were dissected and prepared for histological examination by light and electron microscopy. The number of fetuses and their weights were recorded. Results: There was a significant decrease in the overall body weight in both TAM treated groups (GD20 and PND7) when compared with the control group. TAM treatment in (PND7) induced significant increase in serum levels of kidney biomarkers, creatinine, urea, and uric acid. Microscopic examination of the kidnies of both (GD20) and (PND7) treated groups, revealed small atrophied glomeruli. Some of them appeared shrunken with dilated capsular space. The proximal and distal tubules were swollen with loss of some of their nuclei. Many areas of focal necrosis were seen with tubular degeneration, partial loss of the luminal brush border. Ultrastructural results in (PND7) treated group, the glomeruli appeared immature. The renal corpuscles showed the endothelial cells was detached at certain points some of their fenestrations were obliterated, focal fusion of podocytes foot processes and irregular thickening of glomerular basement membranes. Conclusion: Tamoxifen induced developmental structural changess in the kidney during pregnancy and breast feeding. Therefore, tamoxifen should not be prescribed for either pregnant or lactating mothers.

Keywords: Kidney, tamoxifen, prenatal, postnatal development, rat.