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The role of poly (ADP-ribose) polymerase-1 inhibitors: Prevention of non glutathione-dependent carbon tetrachloride-induced hepatotoxicity

Carbon tetrachloride (CCl4) is a hepatotoxicant known to elevate alanine aminotransferase (ALT) and other liver enzyme levels, and cause lipid peroxidation, as well as centrilobular necrosis. A number of poly ADP-ribose polymerase (PARP) inhibitors were administered via intraperitoneal (i.p.) injections to male ICR mice as cotreatments at various time intervals relative to the CCl4. Aminophylline, a water soluble complex consisting of two molecules of theophylline bridged by ethylene diamine, was administered one-half hour, one hour and two hours after CCl4. The levels of ALT in the serum, as well as malondialdehyde and its equivalent markers of oxidative damage in the liver, were significantly reduced by aminophylline, relative to those in mice receiving only CCl4. The hepatoprotective effects of aminophylline were confirmed via the examination of histopathologic samples from the livers of mice receiving aminophylline in conjunction with CCl4 as opposed to those administered CCl4 alone. The potential benefit to society as a result of this research is that aminophylline, which has already been approved by the Food and Drug Administration (FDA), could potentially be administered in the event of an overexposure to CCl4 or similar halocarbons to minimize the free radical-mediated hepatotoxicity resulting from overexposure.

Identiferoai:union.ndltd.org:USF/oai:scholarcommons.usf.edu:etd-3191
Date01 June 2007
CreatorsGrivas, Paul Christopher
PublisherScholar Commons
Source SetsUniversity of South Flordia
Detected LanguageEnglish
Typetext
Formatapplication/pdf
SourceGraduate Theses and Dissertations
Rightsdefault

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