Woudenberg-Vrenken, Titia E. published the artcileAnti-oxidants do not prevent bile acid-induced cell death in rat hepatocytes, Safety of SU6656, the publication is Liver International (2010), 30(10), 1511-1521, database is CAplus and MEDLINE.
Background: Bile acids, reactive oxygen species (ROS) and inflammatory cytokines are crucial regulators of cell death in acute and chronic liver diseases. The contribution of each factor to hepatocyte death, either apoptosis or necrosis, has not been clarified as yet. It has been suggested that the generation of oxidative stress by bile acids contributes to hepatocyte death during cholestasis and bile acid toxicity, although the beneficial role of ROS prevention in bile acid-mediated cell death is not fully understood. Aim: Study the effects of anti-oxidants in bile acid-induced cell death in vitro. Methods: Primary rat hepatocytes were exposed to the bile acids glycochenodeoxycholic acid (GCDCA) or taurolithocholic acid-3 sulfate in the absence or presence of ROS scavengers or anti-oxidants. Heme oxygenase (HO)-1 mRNA levels were analyzed by quant. polymerase chain reaction. Apoptosis was quantified by acridine orange staining and caspase-3 activity assay. Necrosis was detected by Sytox green staining. Results: Anti-oxidants do not attenuate bile acid-induced cell death. Furthermore, bile acid exposure does not enhance the mRNA expression of the oxidative stress-responsive gene HO-1. The Src-kinase inhibitor, SU6656, does reduce GCDCA-induced apoptosis and necrosis. Conclusions: In hepatocytes, bile acid-induced toxicity is not prevented by scavengers of oxidative stress. The beneficial effects observed in patients might be because of the contribution of ROS and cytokines rather than bile acid-mediated oxidative stress. However, the use of specific Src kinase inhibitors might be a useful tool to prevent bile acid-induced injury in liver diseases.
Liver International published new progress about 330161-87-0. 330161-87-0 belongs to indole-building-block, auxiliary class Protein Tyrosine Kinase/RTK,Src, name is SU6656, and the molecular formula is C3H9ClOS, Safety of SU6656.
Referemce:
https://www.nature.com/articles/s41429-020-0333-2,
Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles