Possible Interaction: Azathioprine and Glutathione

“Further, glutathione participates in the formation of toxic metabolites of such chemotherapeutics as azathioprine and bleomycin and may affect the cellular uptake of other agents, such as methotrexate.”

“ Azathioprine is known to induce glutathione depletion and consumption of glutathione is greater in cells with high glutathione‐S‐transferase (GST) activity compared with those with low activity; moreover, some reports indicate that GST might play a direct role in the reaction of glutathione with azathioprine.”

“The uncatalyzed reaction of azathioprine with glutathione was estimated to be less than 1% of the GST-catalyzed biotransformation.”

“The parent compound is azathioprine AZA ), which is rapidly reduced in the presence of glutathione to 6-mercaptopurine (6-MP) and then metabolized into active metabolites with immune-modifier activity.”

“Intraperitoneal … of azathioprine (50 mg/kgB.W.) induced a significant decrease in RBCs count, Hb …, PCV%, WBCs count, differential count and platelet count, hepatic antioxidant enzymes (reduced glutathione and glutathione s-transferase) and increase of serum transaminases (alanine aminotransferase and aspartate aminotransferase enzymes) activities, alkaline phosphatase and malondialdehyde formation.”

“This effect was evident through reducing malonialdehyde levels and releasing the inhibitory effect of Azathioprine on the activities of glutathione , catalase and superoxide dismutase.”

“Thus, AZA has been proved to be genotoxic, and the genotoxicity is likely to be protected by GSH present in hepatocytes, suggesting that GSH depletion potentiates the carcinogenic effect of AZA.”

“ Azathioprine decreased the viability of hepatocytes and induced the following events: intracellular reduced glutathione ( GSH ) depletion, metabolic activity reduction, and lactate dehydrogenase release.”

“Thus, the liver plays a major role in the metabolism of azathioprine through the interaction of the drug with glutathione.”

“It was shown that biogenic thiols such as glutathione or cysteine facilitate the first and crucial step of azathioprine metabolism , due to the presence of COO(-), SH, and NH(3)(+) groups in their molecules.”