title: Inhibition of lipopolysaccharide-induced liver injury in rats treated with a hepatic drug-metabolizing enzyme inducer p,p'-DDT.
abstract: Hepatocellular hypertrophy in association with drug-metabolizing enzyme induction is considered to be an adaptive change associated with drug metabolism. To improve our understanding of liver hypertrophy, we determined the effect of a single ip injection of either lipopolysaccharide (LPS) or vehicle in male F344 rats with hepatocellular hypertrophy induced by oral delivery of p,p'-DDT for 2 weeks. The rats were sacrificed 3h or 24h after LPS or vehicle injection. LPS induced a focal hepatocellular necrosis in rats fed the control diet. When rats pre-treated with p,p'-DDT were injected with LPS, necrotic foci surrounded by ballooned hepatocytes were observed in the liver. The change was consistent with reduced LPS-mediated increases in plasma hepatic biomarkers, neutrophil influx, and apoptosis, and also associated with hepatic mRNA levels of TNF-α, CYPs, and NOS2. By contrast, when combined with p,p'-DDT and LPS, faint hepatocellular fatty change was extended, together with a synergistic increase in total blood cholesterol. These results suggest that hepatocytes exposed to p,p'-DDT are protected from the cell-lethal toxic effects of an exogenous stimulus, resulting in cell ballooning rather than necrosis in association with reduced inflammation and apoptosis, but compromised by an adverse effect on lipid metabolism.
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Tomita
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan. Electronic address: yoshida7@cc.tuat.ac.jp.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Fukuyama
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Katoh
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Ohnuma-Koyama
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Katsumi
authors.initials: K
authors.lastname: Soma
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Sayuri
authors.initials: S
authors.lastname: Kojima
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ohtsuka
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Makio
authors.initials: M
authors.lastname: Takeda
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Maki
authors.initials: M
authors.lastname: Kuwahara
authors.affiliation: Institute of Environmental Toxicology, Uchimoriya-machi 4321, Joso-shi, Ibaraki 303-0043, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Harada
mesh_terms: D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D003634:DDT / Q000633:toxicity*; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D008070:Lipopolysaccharides; D003634:DDT
keywords: Apoptosis; Hepatocellular hypertrophy; Hepatocellular necrosis; Inflammation; Lipopolysaccharide; Steatosis; p,p′-DDT