Critical role of lipid peroxidation in carbon tetrachloride-induced loss of aminopyrine demethylase, cytochrome P-450 and glucose 6-phosphatase

Effects of 8-(2-Dimethylaminoethyl)-3-Oxo-4-Phenyl-1-Thia-4,8-Diazaspiro [4,5] Decane Dihydrochloride Monohydrate (Y-8845) on Carbon Tetrachloride-Induced Liver Injury

“…The mechanism of the protective action of Y-8845 is unclear at present. It is reported that the destruction of G6Pase of cytochrome P-450 by CC14 in vivo correlated with the enhancement of lipid peroxidation (16). Therefore, the protective effect of Y-8845 against CC14 hepatotoxicity observed in this study might be partly ascribable to anti-peroxidation properties.…”

The apparent loss of cytochrome P-450 associated with metabolic activation of carbon tetrachloride.

“…5). Glende et al (3) proposed that the degradation of cytochrome P-450 was induced solely by lipid peroxidation which was initiated by the trichloromethyl radical. As stated above, our results provide further evidence that cytochrome P-450 is degraded directly by interacting with the reductive product.…”

“…One is that cytochrome P-450 heme is degraded by a peroxidative reaction initiated by the trichloromethyl radical, a reactive intermediate formed during the reduction of carbon tetrachloride (2,3). The other is that the trichloromethyl radical binds covalently to cyto chrome P-450 in a chemical manner via reductive dehalogenation (4).…”

Tissue Occurrence of Carbonyl Products of Lipid Peroxidation and Their Role in Inflammatory Disease

“…a) Effects of the lipid peroxidation on microsomes. The action of toxic compounds on cells leads to a quite rapid swelling of rough and smooth endoplasmic reticulum; the ribosomes dissociate from the rough endoplasmic reticulum and the protein synthesis decreases within less than 30 minutes [5,6]. The inhibition of microsomal glucose-6-phosphatase activity is seen very early In fact CCl4 fission generates free radicals able to trigger the lipid peroxidative process, starting from microsomal membranes.…”

“…This discovery of the stimulation of an enzyme activity by very low doses of 4-hydroxyalkenals represented a clean change in the evaluation of the lipoperoxidative process and of the functions of its end-products. The first experimental studies on the biological effects of the lipid peroxidation supplied a lot of proofs about the inhibition of several enzymes in tissues where the lipid peroxidation rate was stimulated [5] or about the decrease of their activity in tissue homogenates or in subcellular fractions incubated in the presence of high concentrations of HNE [24]. b. Activation of the exocytosis by 4-hydroxynonenal.…”