MRI study of the inhibitory effect of new spin traps on in vivo CCl 4-induced hepatotoxicity in rats

Abstract

Acute CCl 4 hepatotoxicity is thought to occur as a result of free generated from the metabolism of CCl 4 in the liver. With the use of MRI it is possible to detect in vivo a CCl 4-induced edematous region surrounding the major branch of the hepatic portal vein in the right lobe. Inhibition of the CCl 4-induced response has been obtained by pretreatment with the spin trap, PBN, 30 min prior to CCl 4 exposure. The inhibitory effect of two new traps, M 3PO or methyl-DMPO, and PhM 2PO or phenyl-DMPO, on in vivo CCl 4-induced acute hepatotoxicity was investigated. Both PhM 2PO and M 3PO were found to inhibit the CCl 4-induced response at lower concentrations (0.35 M/kg body weight) than PBN (0.70 M/kg body weight). However, both M 3PO and PhM 2PO were also found to induce and edematous response at the same concentrations used for the PBN studies (0.70 M/kg body weight). PhM 2PO, at a concentration of 0.35 M/kg body weight, was 93% as efficient as PBN, at a concentration of 0.70 M/kg body weight; whereas M 3PO, at a concentration of 0.35 M/kg, was 89% as efficient as PBN at 0.70 M/kg body weight. Electron micrographs were obtained from small liver sections taken in proximity to the major branch of the hepatic portal veins of all treatment groups. The electron microscopy investigations support the MRI findings.