Use of Nitroxides as MRI Contrast Agents to Study in vivo Carbon Tetrachloride Induced Hepatotoxicity in Rats

Abstract

CCl₄ and related compounds, such as halothane, are metabolized by the liver to form free radical intermediates, which are thought to be implicated in the hepatotoxic response. Two to three hours following CCl₄ exposure (i.p.) there is a localized edematous region surrounding the portal vein which is observable by proton MRI in vivo. Enhancement of the CCl₄-induced edematous region was possible using Gd-DTPA, a paramagnetic contrast agent. However, with the use of a nitroxide contrast agent (3-PCA) there was no enhancement, but rather a significant diminution of the CCl₄-induced edematous response. These results suggest that the nitroxide contrast agents, which are themselves free radicals, act as free radical scavengers and therefore reduce the formation of the CCl₄-induced hepatic 'damage' observed in proton MR images.

Key Words:

• carbon tetrachloride (CCl₄)
• hepatotoxicity
• in vivo
• magnetic resonance imaging (MRI)
• contrast agents
• 3-carboxy-pyrrolidine-N-oxyl (3-PCA)
• gadolinium diethylene triamine pentaacetic acid (Gd-DTPA)