Fig. 3.
Identification and application of TGx biomarkers for assessing glutathione depletion. A model case for identifying the candidate TGx biomarkers associated with glutathione depletion-type (acetaminophen-type) liver injury is presented. Rats were treated with a glutathione depletor L-buthionine (S, R)-sulfoximine (BSO), and GeneChip analysis was conducted on the liver. (A) A total of 69 probe sets were identified whose signal values were inversely correlated with the hepatic glutathione content. (B) The validity of the 69 probe sets as candidate TGx biomarkers for evaluation of glutathione depletion was evaluated by PCA using time-course microarray data for rat livers treated with acetaminophen. The 69 probe sets clearly classified the animal groups following acetaminophen treatment, and the acetaminophen group was clustered for 24 h together with the BSO-treated rats, suggesting that glutathione homeostasis was highly affected at this time point. Reprinted from Reference113, with permission from Elsevier.