Anti-Inflammatory Properties of N-Phenylanthranilic Acid Derivatives in Relation to Uncoupling of Oxidative Phosphorylation

Saeki, Kiyomi; Muraoka, Saburo; Yamasaki, Hidemasa

doi:10.1254/jjp.22.187

Cited by 10 publications

(3 citation statements)

References 27 publications

(19 reference statements)

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“…Both are likely, therefore, to have interfered with ATP production. This probably explains their ability to potentiate the SI-induced depletion of the stores of ATP (Table 3), an action likely to have been due in part at least to the activation of a mitochondrial ATP-ase enzyme (Saeki et al, 1972;McDougall et al, 1983).…”

Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia

Northover

1989

British J Pharmacology

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Polytechnic, Leicester LE1 9BH 1 Rat isolated and superfused atria weie exposed to a lactate-containing solution simulating the composition of extracellular fluid during myocardial ischaemia (SI). 2 Atria subjected to SI showed a decreased adenosine 5'-triphosphate (ATP) content, a rise in diastolic tension, a diminished conduction velocity of action potentials and shortened refractory periods. All these changes were less pronounced during lactate-free SI. 3 Atria preloaded with calcium displayed exaggerated responses measured electrically and mechanically during exposure to SI, whereas atria previously depleted of calcium displayed diminished electrical and mechanical responses to SI. Neither calcium loading nor calcium depletion modified the SI-induced depletion of the atrial stores of ATP. 4 Sulphinpyrazone protected atria against all aspects of the response to SI, but failed to protect the muscle under conditions of lactate-free SI. It is concluded that during SI, sulphinpyrazone protects against a lactate-mediated inhibition of the glycolytic synthesis of ATP. 5 Flufenamate exaggerated all responses of the atria to SI. These deleterious actions were still observed during lactate-free SI. It is concluded that flufenamate inhibits the synthesis of ATP in the mitochondria. IntroductionSimulated ischaemia (SI) is said to exist when a tissue is exposed in vitro to a solution the composition of which resembles that found extracellularly in regions of ischaemia. During SI in rat atrial muscle the conduction velocity (CV) of action potentials is reduced, as are the durations of both action potentials and refractory periods. These responses are accompanied by progressive contracture development and a characteristic pattern of structural changes, notably in the mitochondria (Northover & Northover, 1988). Return of the myocardium to a solution of normal composition gradually reverses all of these changes. Pretreatment of the atria with sulphinpyrazone protects the myocardium during SI, but flufenamate, another non-steroidal antiinflammatory agent, has a deleterious action (Northover & Northover, 1988).A rise in the diastolic concentration of Ca in the myoplasm is believed to represent an important stage in the series of events responsible for the structural and functional changes observed during SI (Northover & Northover, 1988). In some of the present experiments the diastolic Ca concentration in the myoplasm has been deliberately elevated before exposure to SI. By noting which components of the response to SI were enhanced under these circumstances evidence was obtained concerning the ways in which Ca is involved as a mediator.Lactate is another substance known to accumulate in the ischaemic myocardium (Neely & Grotyohann, 1984), and is an ingredient of the fluid used to produce SI. Moreover, lactate is known to potentiate some of the functional changes in the atria produced by the other ingredients of this fluid (Northover, 1987). Under certain circumstances lactate is known to inhibit glycolysis (Rovetto et al...

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Section: Non-steroidal Anti-inflammatory Drugsmentioning

confidence: 99%

The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia

Northover

1989

British J Pharmacology

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“…Depending on the methods and conditions, the following different values of pK a2 were obtained i.e. : 3.85 (value determined theoretically) [31], 3.97 (capillary electrophoresis) [32], 4.91 (capillary isotachophoretic) [33], 5.0 (spectrophotometric method) [34], 5.84 (potentiometric method in the acetone (5-10%) + water system) [35], and 5.94 (potentiometric method in the ethanol (50%) + water system) [36]. The dissociation constants K a1 and K a2 are expressed by Eqs.…”

Section: Resultsmentioning

confidence: 99%

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Zapała

2011

J Solution Chem

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In this paper, the flufenamic acid equilibria in aqueous solution and in two-phase organic solvent + aqueous solution are described and presented. The dissociation constants K a1 and K a2 were determined in MDM + water mixtures. The Yashuda-Shedlovsky extrapolation procedure has been used to obtain the values of K a1 and K a2 in aqueous solutions. The distribution ratio D was measured in the toluene + water system over a wide range of pH by the shaking flask method. Based on the results of potentiometric titrations in two-phase organic solvent (benzene, ethylbenzene, toluene, carbon tetrachloride, chloroform, chlorobenzene, and bromobenzene) + aqueous systems, and using models of single and multistep equilibria, the values of distribution constants K D and dimerization constants K dim were calculated. The influences of polarity of the applied solvents and pH of the aqueous phase, on the speciation of the particular forms of flufenamic acid in both phases, were demonstrated.

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“…Each animal was lightly anesthetized by ether inhalation, A dose of 0.05 ml of adjuvant mixture was injected intradermally under the volar surface of the left hind paw. The displacement volume of each hind paw was measured prior to and every week after adjuvant injection by the mercury displacement method described previously [7].…”

Section: Induction and Evaluation Of Adjuvant Arthritismentioning

confidence: 99%

Decrease in peritoneal mast cell count in rats with adjuvant arthritis. I. Time course and interstrain difference

1980

Self Cite

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Adjuvant was injected into the left hind paw of Sprague-Dawley (SD) and Wistar rats. In SD rats a marked decrease in the mast-cell count and histamine content of the peritoneal fluid and a significant increase in the histamine content as well as the mast-cell count in the mesentery appeared between 1 and 2 weeks after adjuvant injection. This period approximately coincided with that of the development of secondary inflammatory lesions such as polyarthritis. The adjuvant-induced changes in the peritoneal fluid were more marked in SD than in Wistar rats, corresponding to more intense adjuvant arthritis in the SD strain. In Wistar rats a tendency towards an increase in the histamine content of the mesentery was observed from 2 weeks after adjuvant injection. Adjuvant injection did not have any significant effect on the histamine content of the caecum or the skin of either strain. These results show that adjuvant causes a redistribution of mast cells between the peritoneal fluid and the tissues surrounding the peritoneal cavity probably as a result of delayed hypersensitivity.

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Anti-Inflammatory Properties of N-Phenylanthranilic Acid Derivatives in Relation to Uncoupling of Oxidative Phosphorylation

Cited by 10 publications

References 27 publications

The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia

The involvement of lactate and calcium as mediators of the electrical and mechanical responses of the myocardium to conditions of simulated ischaemia

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Decrease in peritoneal mast cell count in rats with adjuvant arthritis. I. Time course and interstrain difference

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