Characterization of liver injury associated with hypersensitive skin reactions induced by trichloroethylene in the guinea pig maximization test.
Trichloroethylene (TCE) can induce non-dose-related hepatitis, possibly classified as delayed-type hypersensitivity (immune-mediated hepatitis), as well as dose-related toxic liver injury. However, the difference in pathophysiology between the two kinds of hepatitis remains unknown. This study aimed to characterize the liver injury associated with hypersensitive skin reactions induced by TCE in guinea pigs. As a model of dose-related acute toxic liver injury, the animals were treated with intradermal injection (ii) (0, 167, 500, 1500 or 4500 mg/kg of TCE) or dermal patch (dp) (0 or 900 mg/kg of TCE). The guinea pig maximization test (GPMT) was also carried out as a model of immune-mediated liver injury, in which the total TCE dosage was below 340 mg/kg. In the group of TCE 4500 mg/kg (ii), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased (p<0.01), while total protein and globulin decreased (p<0.05). Evident fatty degeneration, hepatic sinusoid dilation and inflammatory cell infiltration were observed. No significant change was found in animals treated with TCE of doses below 500 mg/kg (ii) or 900 mg/kg (dp). In the GPMT, sensitization rates of TCE-induced dermal allergy were 66%. ALT, AST, lactate dehydrogenase and the relative liver weight increased significantly (p<0.05) while albumin, IgA and gamma-glutamyl transpeptidase decreased significantly (p<0.05). Lesions of ballooning changes were observed in liver pathology. Thus, TCE could cause both acute-type toxic liver injury and immune-mediated liver injury, the so-called delayed-type hypersensitivity at doses below the dosage for toxic liver injury. Interestingly, the histopathological features were quite different: fatty degeneration was most prominent in the former, and ballooning in the latter.
Tang
Xiaojiang
X
Guangdong Poison Control Center, Guangzhou, China. river-t@126.com
Que
Bingling
B
Song
Xiangrong
X
Li
Senhua
S
Yang
Xiaojun
X
Wang
Hailan
H
Huang
Hanlin
H
Kamijima
Michihiro
M
Nakajima
Tamie
T
Lin
Yongcheng
Y
Li
Laiyu
L
D000704:Analysis of Variance; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000150:complications / Q000209:etiology* / Q000276:immunology; D016009:Chi-Square Distribution; D017449:Dermatitis, Allergic Contact / Q000150:complications* / Q000209:etiology / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D014241:Trichloroethylene / Q000633:toxicity*
D014241:Trichloroethylene