title: Late administration of dimethyl sulfoxide minimizes the hepatic microvascular inflammatory response to chloroform in rats.
abstract: Dimethyl sulfoxide (DMSO) protects against liver injury elicited by chloroform (CHCl(3)) in rats even when given 24 h after the toxicant. Aminobenzotriazole (ABT) is a cytochrome P-450 inhibitor as is DMSO. The present study was conducted to examine the effect of DMSO or ABT on the hepatic microvascular inflammatory response to CHCl(3) using in vivo microscopy. Rats received 0.75 ml/kg CHCl(3) by oral administration followed 24 h later by either 2.0 ml/kg DMSO, 30 mg/kg ABT, or saline injected intraperitoneally. Untreated animals served as controls. At 28 h after CHCl(3) administration, the number of leukocytes adhering to the sinusoidal wall was significantly increased associated with a reduction in the numbers of perfused sinusoids. DMSO, but not ABT, caused a restoration of perfused sinusoids to 85% of normal. At 32 h after, leukocyte adhesion and Kupffer cell phagocytic activity were significantly increased. The numbers of perfused sinusoids were decreased by 32% in periportal regions and 50% in centrilobular regions. Sinusoidal perfusion and Kupffer cell activity were modified significantly by either DMSO or ABT, while leukocyte adhesion was reduced by DMSO alone. The results suggest that attenuation of the hepatic microvascular response to CHCl(3) is a potential mechanism of post-treatment with DMSO.
authors.affiliation: Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, PO Box 245044, N. 1501 Campbell Ave., 85724, Tucson, AZ, USA
authors.initials: Y
authors.lastname: Ito
authors.initials: RC
authors.lastname: Lind
authors.initials: CK
authors.lastname: Begay
authors.initials: AJ
authors.lastname: Gandolfi
authors.initials: MK
authors.lastname: McCuskey
authors.initials: RS
authors.lastname: McCuskey