Effect of "drugs for liver disease" on hepatotoxic action of carbon tetrachloride. III. Effect of protoporphyrin and phosphorylcholine on injured microsomal membrane.

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Abstract
An attempt was 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 (CCl4) intoxication, by measuring UV absorbance, IR spectroscopy, circular dichroism (CD) and RNA content, and by using some hydrophobic probes, 1-anilinonaphthalene-8-sulfonate (ANS) and 2,4,6-trinitrobenzenesulfonate (TNBS). Administration of PC to CCl4-poisoned rats decreased the increased nonribosomal RNA content of the microsomes at 5 days. ANS binding to microsomes changed little in all groups. A double reciprocal plot of ANS binding to the microsomes indicated that the affinity of the membrane of all groups for ANS was not affected by CCl4 or the drug administrations. TNBS binding to the membrane aminophospholipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE) decreased in CCl4-poisoned rats at 2 and 5 days, by 21-25% for PS and 25-34% for PE, as compared with control rats, indicating a significant alteration of the phospholipid composition in the membrane. PC administration for 8 days increased its binding to both aminophospholipids. From CD spectra examination of the membrane, CCl4 administered caused partially conformational changes of the proteins, significant at 5 days; PC administration to poisoned rats for 5 days returned the structure to the normal levels. A semigraphical method of CD data analysis exhibited that the membrane contained approximately 55% .alpha.-helix, 21% .beta.-structure and 24% unordered structure; CCl4 administration decreased the helix content by 9% without significant alteration of .beta.-structure. IR spectra indicated that the membrane contained .beta.-structure. PP had no appreciable effects on the membrane structure. PC has an excellent reconstructive action of phospholipid and protein structures of the injured microsomal membrane.