ISSN: 2161-0495
+44 1478 350008
Dhanya Saraswathiamma
Libya
Research Article
Ex vivo Effects of Sorafenib and Regorafenib on Murine Hepatocytes
Author(s): Ali S. Alfazari, Saeeda Almarzooqi, Alia Albawardi, Sami Shaban, Bayan Al-Dabbagh, Dhanya Saraswathiamma, Saeed Tariq and Abdul-Kader SouidAli S. Alfazari, Saeeda Almarzooqi, Alia Albawardi, Sami Shaban, Bayan Al-Dabbagh, Dhanya Saraswathiamma, Saeed Tariq and Abdul-Kader Souid
Sorafenib and regorafenib are structurally-related small-molecular-weight inhibitors of cellular kinases. Regorafenib has a Boxed Warning stating: “Severe and sometimes fatal hepatotoxicity has been observed in clinical trials”, while sorafenib is considered less hepatotoxic. This ex vivo study assessed the effects of sorafenib (2.5 and 50 μM) and regorafenib (5.0 and 50 μM) on liver structure, ultrastructure, cellular respiration (mitochondrial O2 consumption), ATP, caspase activity, urea synthesis, and glutathione. Liver fragments from Taylor Outbred mice were incubated in Krebs-Henseleit buffer (continuously gassed with 95% O2:5% CO2) with and without the drugs for 3 to 4 h. The presence of sorafenib or regorafenib had insignificant effects on liver structure, cellular respiration, ATP, caspase-3 activity, urea synthesis, and glutathione. At 3 h, liver histology w.. View More»
DOI:
10.4172/2161-0495.1000207