Possible Interaction: Glutathione and Doxorubicin Hydrochloride

“High GSH levels can rupture disulfide bonds, resulting in the controlled release of DOX , which will cause necrosis of tumor cells.”

“In addition, a reduction in GSH levels by Dox caused a nuclear factor‐κB dependent enhancement of c‐Myc expression, which led to cAMP‐regulatory element‐binding protein (CREB) activation.”

“The results showed that DOX markedly decreased H9C2 cell viability, increased the levels of CK, LDH, caused histopathological and ECG changes in rats and mice, and triggered myocardial oxidative damage via adjusting the levels of intracellular ROS, MDA, SOD, GSH and GSH-Px.”

“A significantly accelerated release of DOX was triggered by GSH for DOX-loaded SPDP micelles, compared with DOX-loaded SPGS micelles.”

“The introduction of GSH further expedited DOX release.”

“However, the release rate of DOX was markedly increased after the addition of 10mM GSH or in pH5.0 release medium.”

“ Doxorubicin disturbed kidney histology, abrogated renal function tests (serum creatinine, uric acid, and blood urea nitrogen), induced a significant decrease in antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and catalase) and reduced glutathione ( GSH ) content.”

“The in vitro drug release profile showed that DOX release was significantly restricted by the polymer caps at pH 7.4, while it was greatly accelerated upon the addition of GSH.”

“The release of DOX was significantly accelerated at pH5.0 or in the presence of 10mM glutathione (GSH) at pH7.4, in which 62.8% and 74.3% of DOX was released, respectively, in 21h.”

“These results … that although GSH does confer a significant degree of … against the toxic effects of ADR in general, the more specific differences in response to ADR across the cell cycle probably were not the consequence of thiol variations but rather the result of other as yet unidentified factors.”