The Potential Teratogenic Effect of Tilmicosin in Rats: Visceral Malformations and Histomorphological Alterations in Fetal Internal Organs

Abstract

Potential fetal adverse effects are well-known for several antibacterial classes. The present study was performed to evaluate the potential teratogenic effect of Tilmicosin (TMS) antibiotic in Sprague Dawley rats. TMS was daily administered orally to pregnant rats at two dose levels, 250 or 500 mg/kg bw, on 6-15 days of gestation. The morphological or skeletal malformations were non-significantly different from control values. However, visceral examination revealed elevation in the percentage of intrathoracic and intracranial haemorrhages, and kidney hypoplasia (unilateral or bilateral) in fetuses from dams treated with the high dose. In addition, both dose levels produced fetuses with increased percentages of dilated brain ventricles, heart ventricles and renal pelvis. Histopathologically, both TMS doses induced pathological changes in fetal liver and kidney, in a dose-dependent manner. Liver showed hepatocyte hydropic degeneration, congestion of hepatic blood vessels, engorgement of bile canaliculi and dilatation of hepatic lymphatic vessels. Kidney revealed coagulative necrosis of renal tubules and glomerular tuft, adhesion between the parietal and visceral layers of Bowman’s capsule and the glomerular tuft became ring shape with the presence of multiple layer glomerular tufts. In conclusion, TMS antibiotic has the potential to induce teratogenic effects (mainly visceral) and pathological changes in liver and kidneys tissues of rat fetuses when administered during the organogenesis period. This result demonstrated the ability of TMS to pass the placental barrier.