Possible Interaction: Glutathione and Mechlorethamine

“…,glutathione plays a role in the detoxification and repair … cellular injury by such diverse agents as mechlorethamine , melphalan, cyclophosphamide, nitrosoureas, 6-thiopurine, 4'-(9-acridinylamino)methanesulfon-m-anisidide, the quinone antibiotics (including Adriamycin, …, and mitomycin C), the sesquiterpene lactones (such as vernolepin), and other sulfhydryl-reactive diterpenes (like jatrophone).”

“ HN2 , however, inhibited glutathione reductase and blocked the free sulfhydryl group of GSH by forming serveral addition products of alkylated GSH.”

“This study demonstrates that bcl-2 and glutathione are up-regulated by HN2 and links this to a previously unexplained 31P MRS phenomenon: increased NTP after chemotherapy.”

“ GSH depletion significantly potentiated the cytotoxicity of L-phenylalanine mustard, chlorambucil, and mechlorethamine as determined by clonogenic assay on plastic plates.”

“ HN2 covalently modifies macromolecules such as DNA, RNA, and proteins or is scavenged by glutathione , forming adducts that can contribute to toxicity.”

“Depletion of GSH in the hepatocytes markedly increased their susceptibility to HN2.”

“Moreover, nitrogen mustard incubated with GSH and glutathione transferase was 4-fold less cytotoxic than nitrogen mustard incubated with GSH alone.”