Use of nitroxides as MRI contrast agents to study in vivo carbon tetrachloride induced hepatotoxicity in rats.

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.