Barbara Sawyer

Studies on succinate-tetrazolium reductase systems: III. Points of coupling of four different tetrazolium salts III. Points of coupling of four different tetrazolium salts

An investigation has been made of the points of coupling between four tetrazolium salts and the respiratory chain (succinate to O2) in rat-liver tissue suspensions. Each tetrazolium salt has been studied with four levels of tissue and under various incubation conditions. The effects of various respiratory-chain inhibitors on these reactions have been studied in order to localise where the tetrazolium salts are reacting with the respiratory chain. The reaction of nitro-blue tetrazolium with the respiratory chain is virtually insensitive to the presence of antimycin A, or to the level of O2 in the incubation mixture. This and other evidence suggests that nitro-blue tetrazolium reacts almost completely at one site on the respiratory chain, possibly ubiquinone. C,N-diphenyl-N′-4,5-dimethylthiazol-2-yltetrazolium bromide, however, appears to react at two sites of roughly equal importance, one of which is sensitive to antimycin A; this latter site is in the region of cytochrome c. Of the other two tetrazolium salts investigated here, triphenyltetrazolium chloride reacts with the terminal oxidase, and 2-p-nitrophenyl-3-p-iodophenyl-5-phenyltetrazolium chloride reacts in a manner similar to C,N-diphenyl-N′-4,5-dimethylthiazol-2-yltetrazolium bromide. These results, combined with the results for neotetrazolium chloride in the preceding communication, are discussed in terms of previous reports in the literature and the applicability of using tetrazolium reduction for histochemical purposes.

Biochemical and structural changes in rat liver resulting from the parenteral administration of a large dose of sodium salicylate

Abstract The effects of a large parenteral dose of sodium salicylate on rat liver and plasma enzymes have been studied. A dose of 400 mg/kg by i.p. injection did not result in significant elevation of three plasma enzymes investigated: β-glucuronidase, acid phosphatase and alanine aminotransferase. There was, however, a rapid decrease in the livers concentration of NADPH 2 and a similarly rapid choleresis. Although the total concentration of ATP in the liver was not altered by salicylate dosing the distribution between the large particle fraction and the cell sap was changed in favour of there being relatively more ATP in the cell sap fraction. Sodium salicylate produced only a small change in the microsomal cytochrome P 450 spectrum in vitro in comparison with the effects found with the drug SKF 525A that is known to bind strongly to P 450 . Liver sections obtained from rats dosed 1–3 hr previously with salicylate appeared relatively normal when examined by light microscopy. Electron microscopy, however, demonstrated several early effects of salicylate on liver parenchyma: there appeared to be an early increase in the number of peroxisomes, and multivesicular bodies were in evidence around the Golgi zone. The endoplasmic reticulum and attached ribosomes exhibited a normal appearance. These effects of salicylate on rat liver are discussed and contrasted with the results found previously with known hepatotoxic agents.

Liver NADP and NADPH2 in liver necrosis induced by carbon tetrachloride: The modifying action of protective agents

Abstract An investigation has been made of a previous speculation that the decreased content of NADP + NADPH 2 in rat liver 1 hr after the administration of carbon tetrachloride is associated with the sequence of events that progress to necrosis. A variety of agents have been administered together with the carbon tetrachloride to produce modifications in the extent of centrilobular necrosis present 24 hr later. The effects of such treatments on the level of NADP + NADPH 2 in the liver 1 hr after dosing have been determined. It has been found that substances (Phenergan; Cetab; Nupercaine) that substantially delay the appearance of centrilobular necrosis (assessed histologically 24 hr after dosing) also prevent the drop in liver NADP + NADPH 2 that normally occurs 1 hr after administering carbon tetrachloride. Several agents (Benadryl; Anthisan; SKF-525A) that were partially protective in terms of delaying necrosis also prevented the nucleotide change. On the other hand, several agents (dodecyl sulphate, desferral, and propyl gallate) did not inhibit either the appearance of necrosis or the decreased nucleotide content. Two substances, phenobarbitone and cysteamine, were found to have no significant effect on the development of necrosis yet prevented the nucleotide decrease. It is argued that the explanation of this effect lies in the transient nature of the protective action possessed by these materials. The evidence obtained in this study is consistent with the previous speculation that the nucleotide decrease and the developments of necrosis are related in this type of liver injury.

DEOXYRIBONUCLEIC ACID AND RIBONUCLEIC ACID CONTENT OF HUMAN TISSUES OBTAINED AT NECROPSY.

Values for the deoxyribonucleic acid and ribonucleic acid contents in a considerable number of human post-mortem tissues are given and briefly discussed.