Effect of"Drugs for Liver Disease"on Hepatotoxic Action of Carbon Tetrachloride. III. Effect of Protoporphyrin and Phosphoryl-choline on Injured Microsomal Membrane

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An attempt has been made to clarify the action of drugs for liver disease, protoporphyrin (PP) and phosphorylcholine (PC) on the structure of liver microsomal membrane during carbon tetrachloride (CCl_4) intoxication, by measuring ultraviolet (UV) absorbance, infrared (IR) spectroscopy, circular dichroism (CD) and ribonucleic acid (RNA) content, and by using some hydrophobic probes, 1-anilinonaphthalene-8-sulfonate (ANS) and 2,4,6-trinitro-benzenesulfonate (TNBS). Administration of PC to CCl_4-poisoned rats was found to decrease the increased nonribosomal RNA content of the microsomes at 5 days, to some extent. ANS binding to microsomes little changed in all groups. A double reciplocal plot of ANS binding to the microsomes indicated that the affinity of the membrane of all groups for ANS was not affected by CCl_4 or the drug administrations. TNBS binding to the amino-phospholipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE), however, on the membrane was extremely decreased in CCl_4-poisoned rats at 2 and 5 days, by 21-25% for PS and 25-34% for PE, as compared with those of control rats, indicating a significant alteration of the phospholipid composition in the membrane. Administration of PC for 8 days produced a significant increase in its binding to both aminophospholipids. It was found from CD spectra of the membrane that CCl_4 administered caused partially conformational changes of the proteins, significant at 5 days, and administration of PC to the poisoned rats for 5 days recovered the decreased ordered structure to the nativelevel. A semigraphical method of CD data analysis exhibited that the membrane contained approximately 55% α-helix, 21% β-structure and 24% unordered structure and CCl_4 administration decreased the helix content by 9% without significant alteration of β-structure. IR spectra also indicated that the membrane contained β-structure. PP had no appreciable effects on the structure of the membrane. Thus, it is concluded that PC has an excellent reconstructive action of phospholipid and protein structure of the injured microsomal membrane.
公益社団法人日本薬学会の論文
1976-08-25

Effect of"Drugs for Liver Disease"on Hepatotoxic Action of Carbon Tetrachloride. III. Effect of Protoporphyrin and Phosphoryl-choline on Injured Microsomal Membrane

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