Evaluation of caspase-dependent apoptosis during fluoride-induced liver lesion in pigs.
Sixteen barrows (Duroc x Landrace x Yorkshire) were randomly divided into two groups, each consisting eight pigs. The groups received the same basal diet supplemented with 0 and 400 mg/kg fluoride, respectively. Histological examinations, including in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), Haematoxylin and Eosin staining (HE) and transmission electron microscopy observation, found apoptotic hepatocytes 50 days after additional 400 mg/kg fluoride treatment. The obvious DNA ladder and the significantly increased both hepatic caspase-9 and caspase-3 activity indicated that fluoride induced caspase-dependent apoptosis in vivo. In addition, serum glutamate pyruvate transaminase (GPT) activity and hepatic lipid peroxides (LPO) concentration was significantly increased. The activity of serum glutamate oxaloacetate transaminase (GOT) showed an increased trend. The results suggest that fluoride induces apoptosis by elevating the oxidative stress-induced lipid peroxidation, causing mitochondrial dysfunction and further activating caspase-9 and caspase-3.
Zhan
Xiu An
XA
Feed Science Institute, College of Animal Science, Zhejiang University, No. 268, Kaixuan Road, HangZhou, 310029, People's Republic of China.
Wang
Min
M
Xu
Zi Rong
ZR
Li
Wei Fen
WF
Li
Jian Xin
JX
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress / Q000187:drug effects; D012969:Sodium Fluoride / Q000633:toxicity*; D013552:Swine
D008054:Lipid Peroxides; D012969:Sodium Fluoride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases