Chemoprotective Effects of Two Dithiolthiones and of Butylhydroxyanisole Against Carbon Tetrachloride and Acetaminophen Toxicity

✍ Scribed by Sherry S. Ansher; Patrick Dolan; Ernest Bueding

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 390 KB
• Volume: 3
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840030608

✦ Synopsis

Administration of tert-butyl-4-hydroxyanisole or of two dithiolthiones to female CD-1 mice protected against the acute toxic effects of two hepatotoxic agents, acetaminophen and carbon tetrachloride. Reduced mortality of mice was observed following pretreatment with tert-butyl-4hydroxyanisole or dithiolthiones. Pretreatment reduced or prevented hepatic glutathione depletion produced by these two hepatotoxic agents. Liver damage, i.e., as determined by serum transaminase and sorbitol dehydrogenase activities, was less after pretreatment with tert-butyl-4-hydroxyanisole or dithiolthiones. Administration of dithiolthiones resulted in increased (from four-to over six-fold) activities of liver glutathione-S-transferases.

The anticarcinogenic (1) and antimutagenic (2) properties of the antioxidant butylated hydroxyanisole (BHA) are associated with many biochemical effects (2-4). For example, oral administration of BHA increased glutathione (GSH) levels and enhanced the activities of GSH-S-transferases and other enzymes in many rodent tissues. By contrast, reduction in hepatic acid-soluble GSH levels was observed after administration of two hepatotoxic agents, acetaminophen (5) and carbon tetrachloride (CC1,) (See below).

Recently, we noted that administration of two dithiolthiones produced many biochemical effects similar to those observed with BHA. The two dithiolthiones used in the present study were oltipraz (5-(2-pyrazinyl)-4methyl-1,2-dithiol-3-thione) and anethol dithiolthione (3-(p-methoxyphenyl)-l,2-dithiol-3-thione; ADT).

Oltipraz ADT

If hepatic GSH depletion was related to the toxic effects of acetaminophen (5) and CC14, pretreatment with