Related Experiment Video
Updated: May 26, 2026
Inducing Acute Liver Injury in Rats via Carbon Tetrachloride (CCl4) Exposure Through an Orogastric Tube
Published on: April 28, 2020
Hepatoprotective effects of select water-soluble PARP inhibitors in a carbon tetrachloride model
James D McCluskey1, Dmytro Sava, Stephen C Harbison
1Department of Environmental and Occupational Health, Center for Environmental and Occupational Risk Analysis and Management, College of Public Health, University of South Florida, Tampa, FL 33612, USA.
Background:
Inhibitors of the nuclear enzyme poly (ADP-ribose) polymerase (PARP-1) have been demonstrated to attenuate pathophysiologic conditions associated with oxidative stress, specifically with carbon tetrachloride (CT)-induced hepatotoxicity.
Settings And Design:
In this investigation, we evaluated 3 previously untested water-soluble PARP-1 inhibitors, namely, 3-aminobenzamide (ABA), 5-aminoisoquinolinone (AIQ), and N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide HCl (PJ-34) to determine their efficacy in blocking or attenuating CT-induced hepatotoxicity in male imprinting control region (ICR) mice.
Statistical Analysis:
Indicators of hepatotoxicity were compared with F-tests among groups to determine statistically significant effects. Pearson's correlation coefficients were used to evaluate the correlation between PARP inhibition and the attenuation of hepatotoxicity.
Results And Conclusions:
CT treatment resulted in hepatic cytotoxicity, increased serum transaminase (ALT), lipid peroxidation (MDA), intracellular glutathione (GSH) depletion, increased carbonyl content, and substantially increased PARP-1 activity. CT treatment also produced profound observable hemorrhagic necrosis in the hepatic centrilobular region of ICR mice. Pretreatment with PJ-34, ABA, and AIQ before CT treatment significantly decreased PARP-1 activity in hepatocytes after CT treatment by 3.4, 2.0, and 1.9 times, respectively. Corresponding to this reduction in PARP-1 activity, a significant reduction in the ALT levels and MDA and a reduction in the GSH depletion were observed. Also, there were no visible tissue defects in the liver samples from animals pretreated with individual PARP-1 inhibitors before CT administration. These results demonstrate the efficacy of the 3 previously untested water-soluble PARP-1 inhibitors in attenuating CT-induced hepatocellular toxicity and further characterize the role of PARP-1 activation and oxidative stress among the cascade of events in hepatocellular necrosis induced by CT treatment.
