title: Effects of Kupffer cell depletion on acute alpha-naphthylisothiocyanate-induced liver toxicity in male mice.
abstract: Depletion of Kupffer cells, known to modulate chemical-induced hepatocellular injury, has not been studied with regard to biliary epithelial injury. Here, the authors investigated the effect of Kupffer cell depletion by clodronate on the toxicity of alpha-naphthylisothiocyanate (ANIT), known to injure biliary epithelium as well as hepatocytes. Up to 99% depletion of Kupffer cells occurred in ANIT and liposome-encapsulated clodronate-treated mice. The effect of Kupffer cell depletion was most evident one day following ANIT treatment. Histologically, there was a modest increase in neutrophil infiltration of the bile ducts, hepatocytic necrosis, and microvesicular vacuolization in the ANIT and clodronate-treated mice, but differences between other groups did not persist. Clinical pathology analytes related to the biliary or hepatocellular injury were significantly elevated in ANIT and clodronate-treated mice compared to mice given clodronate only. This was also true for mice given ANIT and empty liposomes in the case of the biliary analytes. However, group means were typically higher for the ANIT and clodronate-treated group than others on the first 2 days following ANIT injection. These findings suggest that Kupffer cell reduction increases hepatobiliary damage due to ANIT treatment.
authors.affiliation: College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27607, USA. john_cullen@ncsu.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Cullen
authors.forename: Brenda
authors.initials: B
authors.lastname: Faiola
authors.forename: David H
authors.initials: DH
authors.lastname: Melich
authors.forename: Richard A
authors.initials: RA
authors.lastname: Peterson
authors.forename: Holly L
authors.initials: HL
authors.lastname: Jordan
authors.forename: Carie L
authors.initials: CL
authors.lastname: Kimbrough
authors.forename: Judith S
authors.initials: JS
authors.lastname: Prescott
authors.forename: Richard T
authors.initials: RT
authors.lastname: Miller
mesh_terms: D015058:1-Naphthylisothiocyanate / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D049109:Cell Proliferation; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology*; D002761:Cholangitis / Q000378:metabolism; D004002:Clodronic Acid / Q000494:pharmacology; D005704:Gallbladder / Q000737:chemistry / Q000473:pathology; D006965:Hyperplasia; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007728:Kupffer Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008081:Liposomes / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D019394:Ki-67 Antigen; D008081:Liposomes; C498355:Mki67 protein, mouse; D004002:Clodronic Acid; D015058:1-Naphthylisothiocyanate