Oxidative stress and liver toxicity in rats and human hepatoma cell line induced by pentachlorophenol and its major metabolite tetrachlorohydroquinone.
Pentachlorophenol (PCP) is a pesticide used worldwide in industrial and domestic applications. It is used extensively as biocide and wood preservatives. Metabolic studies carried out in rodents and human liver homogenates have indicated that PCP undergoes oxidative dechlorination to form tetrachlorohydroquinone (TCHQ). Free radical catalyzed tissue injury is thought to play a fundamental role in human disease. In the present study, we examined the effects of PCP and TCHQ on the induction of lipid peroxidation and liver injury in rats. In addition, the cytotoxic dose, cell death mechanisms and related gene expressions induced by PCP and TCHQ were also determined for human hepatoma cell line (Hep G2). The results indicated that more toxic effects could be observed both in rats and human hepatoma cell line treated with TCHQ than its parent compound, PCP. Oxygen species may be involved in the mechanism of TCHQ intoxication since the urinary 8-epi-PGF2alpha and AST, ALT activities can be induced by TCHQ and attenuated by vitamin E treatment. Apoptosis features were found in cells treated with TCHQ but not PCP. TCHQ-induced cell damage may issue signals for the induction of HSPs, the decrease of the bcl/bax protein ratio and the decrease of CAS gene, whereas the PCP-induced damage may not.
Wang
Y J
YJ
Department of Environmental and Occupational Health, National Cheng Kung University, Medical College, Tainan, Taiwan, Republic of China.
Lee
C C
CC
Chang
W C
WC
Liou
H B
HB
Ho
Y S
YS
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D029563:Cellular Apoptosis Susceptibility Protein; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D028441:F2-Isoprostanes; D006801:Humans; D006873:Hydroquinones / Q000633:toxicity*; D008099:Liver / Q000187:drug effects*; D008297:Male; D018384:Oxidative Stress; D010416:Pentachlorophenol / Q000633:toxicity*; D011506:Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014407:Tumor Cells, Cultured; D014810:Vitamin E / Q000494:pharmacology
D029563:Cellular Apoptosis Susceptibility Protein; D028441:F2-Isoprostanes; D006873:Hydroquinones; D011506:Proteins; D014810:Vitamin E; C075750:8-epi-prostaglandin F2alpha; C044578:2,3,5,6-tetrachlorohydroquinone; D015237:Dinoprost; D010416:Pentachlorophenol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase