Possible Interaction: Chloroquine and Glutathione

“Increasing the GSH levels has been shown to confer resistance to CQ and vice versa.”

“An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ.”

“This differential effect is explained by the ability of chloroquine and amodiaquine to inhibit the degradation of membrane-associated FP by glutathione and the incapacity of quinine and mefloquine to do so.”

“Long-term treatment with these inducers can cause excessive metabolism and deficiency of vitamin D. Prooxidant drugs such as chloroquine , drugs detoxified by conjugation with glutathione, and alcohol can deplete reduced glutathione with consequent effects on amino acid transport and the redox status of cells.”

“In the presence of the full activating system, however, all compounds except chloroquine resulted in depletion of the level of glutathione and were cytotoxic.”

“In the complete medium, chloroquine suppressed incorporation of label into cystine, cysteine and GSH pools after 1 hr.”

“ GSH concentration and SOD, CAT and GPx activities were significantly higher in GT100 + CQ and GT250 + CQ groups compared to the GTE100, GTE250, IC and NC groups (P < 0.05).”

“Increased GSH levels were detected in both, CQ and MQ resistant parasites, when compared to the parental sensitive clone.”

“Furthermore, in some strains of Plasmodium berghei and P. falciparum, chloroquine resistance is accompanied by an increase in glutathione levels and increased activity in GSH-related enzymes.”

“We conclude that, in chloroquine resistant P.berghei, GSH can detoxify hemin within the food vacuole, thus precluding its polymerization and preventing the activity of chloroquine and other quinoline-containing drugs.”