The Clot-Promoting Effect of Soaps of Long-Chain Saturated Fatty Acids*

Botti, Robert E.; Ratnoff, Oscar D.

doi:10.1172/jci104842

Cited by 53 publications

(17 citation statements)

References 16 publications

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“…Caffeic and ferulic acids are ubiquitous; high concentrations of ellagic acid are found in grapes, certain nuts, and strawberry preserves; and chlorogenic acid is found in relatively high concentrations in coffee, apples, and potatoes. Ellagic acid is pharmacologically active and has been found to control hemorrhage in animals (34,35) and humans (36,37), presumably by activating the intrinsic blood coagulation system (38). Hypotensive and sedative effects of ellagic acid have also been reported in rodents (39).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: Exceptional activity of ellagic acid

Wood

Huang

Chang

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

203

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Ferulic, caffeic, chlorogenic, and ellagic acids, four naturally occurring plant phenols, inhibit the mutagenicity and cytotoxicity of (+)-7,8,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P 7,8-diol-9,10-epoxide-2), the only known ultimate carcinogenic metabolite of benzo [a]pyrene. The mutagenicity of 0.05 nmol of B[a]P 7,8-diol-9,10-epoxide-2 in strain TA100 of Salmonella typhimurium is inhibited 50% by incubation ofthe bacteria and the diol epoxide with 150 nmol offerulic acid, 75 nmol of caffeic acid, 50 nmol of chlorogenic acid or, most strikingly, 1 nmol of ellagic acid in the 0.5-ml incubation mixture. A 3-nmol dose of ellagic acid inhibits mutation induction by 90%. Ellagic acid is also a potent antagonist of B[a]P 7,8-diol-9,10-epoxide-2 in Chinese hamster V79 cells. Mutations to 8-azaguanine resistance induced by 0.2 ,AM diol epoxide are reduced by 50% when tissue culture media also contains 2 ,uM ellagic acid. Similar to results obtained with the bacteria, ferulic, caffeic, and chlorogenic acids are approximately two orders of magnitude less active than ellagic acid in the mammalian cell assay. The antimutagenic effects of the plant phenols result from their direct interaction with B[a]P 7,8-diol-9,10-epoxide-2, because a concentration-dependent increase in the rate ofdiol epoxide disappearance in cell-free solutions of 1:9 dioxane/water, pH 7.0, is observed with all four phenols. In parallel with the mutagenicity studies, ellagic acid is 80-300 times more effective than the other phenols in accelerating the disappearance of B[a]P 7,8-diol-9,10-epoxide-2. Ellagic acid at 10 ,M increases the disappearance of B[a]P 7,8-diol-9,10-epoxide-2 by approximately 20-fold relative to the spontaneous and hydronium ion-catalyzed hydrolysis of the diol epoxide at pH 7.0. Ellagic acid is a highly potent inhibitor of the mutagenic activity of bay-region diol epoxides of benzo[a]pyrene, dibenzo[a,h]pyrene, and dibenzo[a,ijpyrene, but higher concentrations of ellagic acid are needed to inhibit the mutagenic activity of the chemically less reactive bay-region diol epoxides of benz [a]anthracene, chrysene, and benzo [c]phenanthrene. These studies demonstrate that ellagic acid is a potent antagonist of the adverse biological effects of the ultimate carcinogenic metabolites of several polycyclic aromatic hydrocarbons and suggest that this naturally occurring plant phenol, normally ingested by humans, may inhibit the carcinogenicity ofpolycyclic aromatic hydrocarbons.Polycyclic aromatic hydrocarbons are relatively inert environmental precarcinogens that must be metabolized by mammalian enzymes to their biologically active products (ultimate carcinogens). Mutagenicity, metabolism, DNA-binding, and tumorigenicity studies during the past 8 years have shown that benzoring diol epoxides, in which the epoxide moiety forms part of the bay region (1, 2) of the hydrocarbons, are ultimate carcinogens of polycyclic hydrocarbons (3-6).Chemical and kinetic studies have demonstrated that bayregion diol epoxid...

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Section: Discussionmentioning

confidence: 99%

Inhibition of the mutagenicity of bay-region diol epoxides of polycyclic aromatic hydrocarbons by naturally occurring plant phenols: Exceptional activity of ellagic acid

Wood

Huang

Chang

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

203

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“…The in vitro studies (table 5a) imply that the presence of Factor XII is not required for this interaction, and provide evidence that hypercoagulable states may result from mechanisms which do not proceed through the initial activation of Factor XII. Recent studies by Botti and Ratnoff 18 also indicate that Factor XI can be activated without the prior participation of Factor XII.…”

Section: Discussionmentioning

confidence: 96%

“…Alexander et al 18 found that endotoxin induces a defect in thromboplastin generation associated with a generalized Schwartzman reaction in the rabbit. They found the defect to be similar to that seen in human Factor XI deficiency, and suggested tentatively that Factor XI was responsible for the "hemophilioid" disorder associated with endotoxin administration to the rabbit.…”

Section: Discussionmentioning

confidence: 99%

Stasis Thrombi Induced by Bacterial Endotoxin

Thomas

Wessler

1964

Circulation Research

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1. In normal rabbits, single intravenous doses of E. coli and Salmonella endotoxin produce an immediate, transient, hypercoagulable state. Venous stasis occurring during such a state allows the formation of massive red thrombi at sites of obstructed blood flow. The duration of stasis required to produce thrombi following endotoxin administration depends in part on the preinfusion silicone clotting time of the rabbit. 2. E. coli endotoxin shortens the recalcification time of platelet-poor plasma obtained from normal subjects and from patients with heredofamilial coagulation defects of Factor XII (Hageman) and Factor IX (plasma thromboplastin component). In contrast, the recalcification time of platelet-poor plasma obtained from patients with Factor XI (plasma thromboplastin antecedent) deficiency is lengthened by endotoxin. It is suggested that the heat-labile plasma factor known to be required for the platelet-endotoxin interaction may be related to Factor XI.

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“…1) Early in vitro studies indicated that individual saturated fatty acids affect thrombogenesis. [2][3][4][5][6][7] Injection of unbound stearic acid (sodium salt) into the systemic circulation of dogs was followed by massive generalized thrombosis and sudden death. 8) However, human studies concerning the effect of oral intake of stearic acid on thrombotic tendency are inconsistent.…”

Section: Introductionmentioning

confidence: 99%