MRI study of the inhibitory effect of new spin traps on in vivo CCl4-induced hepatotoxicity in rats.
Acute CCl4 hepatotoxicity is thought to occur as a result of free radicals generated from the metabolism of CCl4 in the liver. With the use of MRI it is possible to detect in vivo a CCl4-induced localized edematous region surrounding the major branch of the hepatic portal vein in the right lobe. Inhibition of the CCl4-induced response has been obtained by pretreatment with the spin trap, PBN, 30 min prior to CCl4 exposure. The inhibitory effect of two new spin traps, M3PO or methyl-DMPO, and PhM2PO or phenyl-DMPO, on in vivo CCl4-induced acute hepatotoxicity was investigated. Both PhM2PO and M3PO were found to inhibit the CCl4-induced response at lower concentrations (0.35 M/kg body weight) than PBN (0.70 M/kg body weight). However, both M3PO and PhM2PO were also found to induce an edematous response at the same concentrations used for the PBN studies (0.70 M/kg body weight). PhM2PO, 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 M3PO, 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.
Towner
R A
RA
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Canada.
Janzen
E G
EG
Zhang
Y K
YK
Yamashiro
S
S
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003497:Cyclic N-Oxides; D005609:Free Radicals / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D009589:Nitrogen Oxides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013113:Spin Labels
D003497:Cyclic N-Oxides; D005609:Free Radicals; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D002251:Carbon Tetrachloride