Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

Genotype and allele frequencies of isoniazid-metabolizing enzymes NAT2 and GSTM1 in Latvian tuberculosis patients

“…In addition to NAT2, previous reports have shown that GSTM1 null genotype has a modest effect on genetic susceptibility to ATLI [15]. GST is an important phase II detoxification enzyme, which conjugates glutathione with toxic metabolites [23]. The absence of GST activity due to null mutation can lead to accumulation of toxic intermediates leading to liver damage.…”

Genetic variants in antioxidant pathway: Risk factors for hepatotoxicity in tuberculosis patients

“…[18][19][20] In addition, these hepatotoxic metabolites induced the excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the rat hepatocytes after being metabolized by 8 enzymes including CYP2E1. 20,21 In particular, nitric oxide (NO), one of the RNS, is produced by NO synthase (NOS). In the presence of ROS/RNS, the inducible isoform of NOS (iNOS; coded by NOS2A) is upregulated by nuclear factor kappa B in the liver.…”

Genetic polymorphisms of NAT2, CYP2E1 and GST enzymes and the occurrence of antituberculosis drug-induced hepatitis in Brazilian TB patients

“…NAT2 is also responsible Financial support: FAPERJ/PRONEX (E-26/170.0003/2008), FAPERJ Pensa Rio (E-26/110.288/2007), CNPq (308786/2005-0, 350477/1995-7, 306702/2007-0 and 312165/2006for converting acetylhydrazine to diacetylhydrazine, a nontoxic component , Nelson et al 1976, Woodward & Timbrell 1984 (Figure). Glutathione S-transferase (GST), an important phase II detoxification enzyme, is thought to play a protective role as an intracellular free radical scavenger, which conjugates glutathione with toxic metabolites that are generated from CYP2E1 (Sodhi et al 1996). Sulphydryl conjugation facilitates the elimination of metabolites from the body and reduces the toxic effect (Hayes et al 2005) (Figure).…”