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2526645 
Journal Article 
The effects of CCl4 on the content of nicotinamide adenine dinucleotide phosphate in rat liver 
Slater, TF; Sawyer, BC 
1977 
Yes 
Chemico-Biological Interactions
ISSN: 0009-2797
EISSN: 1872-7786 
HEEP/78/02601 
16 
359-364 
English 
16702 
HEEP COPYRIGHT: BIOL ABS. Rats were administered various doses of CCl4 diluted with paraffin. Liver slices were removed and assayed for the effects of CCl4 on NADP or NADPH after various lengths of time. NADPH was very sensitive to CCl4; even small amounts caused a significant decrease in the concentration. The hepatotoxic action of CCl4 is known to be dependent on a metabolic activation of the toxic agent to a highly reactive product, probably the trichloromethyl radical which occurs through an interaction with the NADPH-cytochrome P-450 electron transport chain that is associated with the endoplasmic reticulum and causes a disturbance of the lipid environment of the endoplasmic reticulum, disrupting various neighboring enzymes. Interaction between various flavoproteins and the radical causes loss of the coenzyme activity of various reduced nicotinamide adenine dinucleotides with consequent loss of coenzyme activity. The action of this activated specie seems to effect the central lobular region of the liver and it is speculated that the depletion of NADPH in this region may be to such an extent as to affect the midzone and periportal region of the liver causing profound metabolic disturbances and necrosis. High concentrations of NADPH in the liver may prevent depletion of NADPH and may be a preventive measure against intoxication by CCl4 but in this case, drug metabolism utilizing the cytochrome-P 450 system may become limited.