Identification of the Toxicity Pathways Associated With Thioacetamide-Induced Injuries in Rat Liver and Kidney.

Identification of the Toxicity Pathways Associated With Thioacetamide-Induced Injuries in Rat Liver and Kidney.

Front Pharmacol. 2018;9:1272

Authors: Schyman P, Printz RL, Estes SK, Boyd KL, Shiota M, Wallqvist A

Abstract
Ingestion or exposure to chemicals poses a serious health risk. Early detection of cellular changes induced by such events is vital to identify appropriate countermeasures to prevent organ damage. We hypothesize that chemically induced organ injuries are uniquely associated with a set (module) of genes exhibiting significant changes in expression. We have previously identified gene modules specifically associated with organ injuries by analyzing gene expression levels in liver and kidney tissue from rats exposed to diverse chemical insults. Here, we assess and validate our injury-associated gene modules by analyzing gene expression data in liver, kidney, and heart tissues obtained from Sprague-Dawley rats exposed to thioacetamide, a known liver toxicant that promotes fibrosis. The rats were injected intraperitoneally with a low (25 mg/kg) or high (100 mg/kg) dose of thioacetamide for 8 or 24 h, and definite organ injury was diagnosed by histopathology. Injury-associated gene modules indicated organ injury specificity, with the liver being most affected by thioacetamide. The most activated liver gene modules were those associated with inflammatory cell infiltration and fibrosis. Previous studies on thioacetamide toxicity and our histological analyses supported these results, signifying the potential of gene expression data to identify organ injuries.

PMID: 30459623 [PubMed]