Ultrastructural study of hepatic stellate cells ( Ito cells) after teratogenic drug treatment in pregnancy: Experimental study in Balb/c mice

Introduction-Aim of the study: Ito cells are the hepatic stellate cells in the space of Disse. They play a key role in the development and regeneration of liver. Retinoid analogues are used therapeutically, while hydroxyurea (HU) is an antiretroviral and chemotherapeutic agent. The aim of this study is to evaluate the effect of the above substances on Ito cells’ ultrastructural morphology by TEM observations. Materials-Methods: Six groups of pregnant Balb/C mice were used for the study. All animals were treated on gestational days 10th, 11th, 12th. The first group was treated with All-Trans Retinoic Acid (RA), the second group with Retinyl Palmitate (RP), the third group with a combination of 13-cis RA and RP and the fourth group with HU. The fifth and the sixth groups were the control animals. Animals were sacrificed on the 19th gestational day. Livers from all animals were removed and were properly prepared for TEM observation. Results: Observation of the liver of All-Trans RA treated pregnant animals revealed Ito cell activation. Microbodies similar to peroxisomes and lysosomes were present in their cytoplasm. Similar findings were found in RP treated animals. In the activated stellate cells, the presence of microfibrils around their nuclei appeared with chromatin condensation in the periphery. In the liver of animals treated with a combination of RP and 13-Cis RA, microfibrils in the cytoplasm, fibrosis and extracellular edema were observed around the sinusoids. In the liver of HU treated animals, peroxisomes with different density were observed in the hepatocyte cytoplasm, surrounded by lipid droplets. In the cytoplasm of activated Ito cells, low density peroxisomes were observed. Fibrosis and extracellular edema were observed surrounding the sinusoids among the stellate cells and in the space of Disse. Conclusions: This ultrastructural study indicates that the drugs induced Ito cell activation and caused possibly irreversible damage to liver parenchyma.