Possible Interaction: Glutathione and Isoniazid

“Retrospective study of tuberculosis patients who underwent INH and RFP treatment also revealed an association between the intake of glutathione and a negative ATB-DILI rate.”

“On day 7, isoniazid markedly inhibited the formation clearance of the glutathione and catechol metabolites by 69.7% and 62.2%, respectively.”

“ INH (6 mM) led to decreased catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content but increased ROS and malondialdehyde (MDA) levels.”

“These findings are interpreted in the light of the hypothesis that in INH intoxication there may be a reduction of available axonal glutathione and cysteine due to inhibition of the pyridoxal phosphate-dependent enzymes cystathionine synthetase and cystathioninase.”

“Hepatic thiols and blood glutathione were decreased significantly in INH and RMP treated groups.”

“The glutathione and related thiols were decreased significantly by INH both in blood and liver tissues, indicating a decrease in protective mechanism.”

“ Isoniazid , an inhibitor of cytochrome P450 2E1, protected cells against APAP toxicity and prevented glutathione depletion.”

“The incubation of isolated hepatocytes with isoniazid or acetyl-hydrazine reduced by 20-25% the intracellular GSH content, while a 50% decrease in GSH was present in the cells exposed to iproniazid and isopropyl-hydrazine.”

“The activities of γ-glutamyl-cysteine synthase (GGCS) and GSH synthase (GS) were lowered by 50 and 56 % respectively on the second … growth whenM. smegmatis was grown in a medium supplemented with 1.5 mg INH per L. In 3-day oldM. smegmatis, INH significantly inhibited … of GSH biosynthetic ….”

“ INH caused a significant reduction of nearly 40% in cell recovery compared with control (P < 0.0001), although the co-incubation with either glutathione (GSH, 1mM) or (NAC, 1mM) showed abolition of INH toxicity.”