Tamoxifen induces hepatotoxicity and changes to hepatocyte morphology at the early stage of endocrinotherapy in mice.

摘要: Clinically, hepatotoxicity is an inevitable side effect during long-term endocrinotherapy in breast cancer patients. Various studies have reported the specific mechanism and protective methods for this hepatotoxicity, however, short-term influences of tamoxifen (TAM) on hepatocytes remain to be elucidated. The previous study investigated TAM-induced liver injury at early stage endocrine treatment. Mice were assigned into 2 groups: experiment group was administrated with intraperitoneal (i.p.) injection 6 mg/kg/day TAM weeks, control i.p. physiological saline same dose. Body weights each detected every day, alanine aminotransferase aspartate levels measured 3 days. Small pieces tissues obtained processed protein extraction, biochemical detection histopathological analysis weeks later. results indicated that decreased mice body weights. Morphologically, treatment only microscopic ultrastructural structure hepatic cords became blurred sections regions, although lobules remained visible. Partially, cells swelled spherical shapes. Nuclei appeared pyknotic exhibited uneven chromatin distribution. In addition, it observed transmission electron microscopy nuclei unevenly distributed. majority endowed distinct heterochromatin thick nucleoli. mitochondrial cristae vague disorganized. Finally, western blotting used a significant increase caspase-3 level tissues. conclusion, experiments elucidated (6 mg/kg/day) would cause mice, underlying involved hepatocyte apoptosis.