title: Antioxidant status and GST gene polymorphisms in antitubercular treatment-induced hepatotoxicity patients.
abstract: BACKGROUND
  Hepatotoxicity is a serious adverse effect of antituberculosis treatment (ATT). Glutathione S-transferase (GST) is involved in the detoxification of toxic metabolites produced as a result of ATT, increased oxidative stress and decreased antioxidant levels, and differences in the GST polymorphism may be one of the causes of ATT-induced hepatotoxicity.
  
  
  OBJECTIVE
  This study was undertaken to study the relationship among antioxidant status, oxidative stress and GST gene polymorphisms in the development of ATT-induced hepatotoxicity in Indian patients.
  
  
  METHODS
  Two hundred fifty TB patients attending clinics in the Gastroenterology and Thoracic Department, PGIMER, Chandigarh, were enrolled. Liver marker enzymes, markers of oxidative stress, levels of antioxidants and identification of GSTT1, GSTM1 and GSTP polymorphisms were performed using standard protocols.
  
  
  RESULTS
  Of the 250 patients, 160 were males. Of the 160 males, 18 (11.3 %) had ATT-induced hepatotoxicity and 142 no hepatotoxicity, while of 90 females, 12 (13.3 %) had hepatotoxicity and 78 no hepatotoxicity. Patients who developed ATT-induced hepatotoxicity had significantly higher oxidative stress compared to those who did not develop hepatotoxicity at between 1 and 2 months of treatment. Among antioxidants, catalase did not show any significant difference at 2 and 4 months of treatment. The presence of GSTM1 was higher in hepatotoxicity patients as compared to non-hepatotoxicity patients, while GSTT1 and GST1/M1 were lower.
  
  
  CONCLUSIONS
  Therefore, in this study, the possible association of oxidative stress with ATT-induced hepatotoxicity was observed. A role of the GST polymorphism in ATT-induced hepatotoxicity was also found and thus could possibly identify the groups at highest risk of developing ATT-induced hepatotoxicity.
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. svrana25@hotmail.com.|, House No. 137, Sector 15 A, Chandigarh, 160015, India. svrana25@hotmail.com.
authors.forename: S V
authors.initials: SV
authors.lastname: Rana
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. jassharma29@gmail.com.
authors.forename: J K
authors.initials: JK
authors.lastname: Kamboj
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. indianbhardwaj@gmail.com.
authors.forename: S K
authors.initials: SK
authors.lastname: Sharma
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. rajola23@gmail.com.
authors.forename: R P
authors.initials: RP
authors.lastname: Ola
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. sarojksinha@hotmail.com.
authors.forename: S K
authors.initials: SK
authors.lastname: Sinha
authors.affiliation: Department of Super Specialty Gastroenterology, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, India. kartarsighpgi@hotmail.com.
authors.forename: K
authors.initials: K
authors.lastname: Singh
keywords: Glutathione S-transferase; Hepatotoxicity; Isoniazid; Oxidative stress