Lipid peroxidation and cell death mechanisms in rats and human cells induced by chloral hydrate.
Chloral hydrate (CH) is widely used as a sedative and hypnotic in pediatric medicine. It is also a by-product of water chlorination and a metabolite of trichloroethylene. We examined the toxicological effects and cell death mechanisms of CH in rats and human Chang liver cells and lymphocytes. Monitoring of urinary 8-epi-PGF2alpha and serum levels of TNF-alpha served as index of lipid peroxidation and cytokine stimulation. The results indicated that a single intraperitoneal injection of 100 mg/kg CH in rats led to a nearly five-fold increase in urinary 8-epi-PGF2alpha on day 1, and a mild decrease on day 2 and day 3. The same treatment also induced significantly higher amounts of serum TNF-alpha on day 2 (about seven-fold). When the rats were treated with CH and vitamin E simultaneously, the amount of urinary 8-epi-PGF2alpha and serum TNF- were significantly lower than that in the rats treated with CH alone. CH caused a greater cytotoxic effect in human Chang liver cells than in comparison with lymphocytes. After treatment with CH, apoptosis features were observed in human lymphocytes, but not Chang liver cells. CH-induced cell damage in lymphocytes may offer signals for the induction of caspases activation. Further studies are needed to evaluate the relationship between caspases activation and the cleavage of other death substrates during postmitotic apoptosis in human lymphocytes.
Ho
Y-S
YS
School of Medical Technology, Taipei Medical University, Taiwan.
Ma
H-Y
HY
Chang
H-Y
HY
Wei
B-L
BL
Lee
C-C
CC
Ho
S-Y
SY
Guo
H-R
HR
Wu
T-P
TP
Chang
W-H
WH
Wang
Y-J
YJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D002697:Chloral Hydrate / Q000009:adverse effects*; D015237:Dinoprost / Q000031:analogs & derivatives*; D028441:F2-Isoprostanes / Q000652:urine; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects*; D007274:Injections, Intraperitoneal; D015227:Lipid Peroxidation / Q000187:drug effects*; D008099:Liver / Q000166:cytology; D008214:Lymphocytes; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000652:urine
D028441:F2-Isoprostanes; D006993:Hypnotics and Sedatives; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D002697:Chloral Hydrate; D015237:Dinoprost