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Organic hydroperoxides such as tert-butyl hydroperoxide (TBHP) are cytotoxic to suspensions of isolated hepatocytes. The exact mechanism of toxicity is unknown but may involve peroxidation of cellular lipids, alkylation of cellular macromolecules, or alterations in cellular calcium homeostasis. These studies were designed to examine lipid peroxidation as a mechanism of organic hydroperoxide-induced cell death. Hepatocytes isolated from mice were more susceptible to the cytotoxic effects of TBHP than were rat hepatocytes. TBHP-induced cell death was preceded by malondialdehyde formation which was also greater in mouse than rat hepatocytes. Species differences in lipid peroxidation were due to intrinsic properties of hepatocyte membranes as lipids isolated from mouse liver and peroxidized with iron/ascorbate formed approximately eightfold more malondialdehyde than lipids isolated from rat liver. Initiation of lipid peroxidation in mouse and rat hepatocytes with iron/ascorbate caused the formation of malondialdehyde equal to that seen with TBHP and a slight depletion of cellular GSH. As with TBHP, malondialdehyde formation induced by iron/ascorbate was greater in mouse than in rat hepatocytes. However, iron/ascorbate had no effect on hepatocyte viability or morphology from either species. Furthermore, TBHP-induced malondialdehyde and ethane formation in isolated rat hepatocytes were completely blocked by promethazine whereas cell toxicity was altered only slightly. Therefore, these data do not support a role for lipid peroxidation in the acute cytotoxicity of TBHP to suspensions of isolated rat hepatocytes.
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
May 1982,
Research communications in chemical pathology and pharmacology,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
September 1999,
Indian journal of experimental biology,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
January 1975,
European journal of biochemistry,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
October 1994,
Free radical biology & medicine,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
August 1986,
Pharmacological research communications,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
November 1978,
Toxicology and applied pharmacology,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
July 1985,
Journal of molecular and cellular cardiology,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
January 1992,
Archives of toxicology,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
November 1975,
European journal of biochemistry,
G F Rush, and
J R Gorski, and
M G Ripple, and
J Sowinski, and
P Bugelski, and
W R Hewitt
January 1982,
Biochemical pharmacology,
