Effects of malotilate on rat erythrocytes.

Akahane, Kouichi; Furuhama, Kazuhisa; INAGE, Fujiroh; Onodera, Toshiyuki

doi:10.1254/jjp.45.15

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…Average life spans from 40 to 100 days were reported. In some more recent publications (13)(14)(15)(16), elimination was measured up to 20 days, semilogarithmic plots were used, and first-order kinetics were assumed. Our values are in good agreement with those reported: 18.7 (15), 14.6 (16), and 13.5 days (17).…”

Section: Elimination Of Hemoglobin Adductsmentioning

confidence: 99%

Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

Neumann

Birner

Kowallik

et al. 1993

Environ Health Perspect

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Arylamines, nitroarenes, and azo dyes yield a common type of metabolite, the nitroarene, which produces a hydrolyzable adduct with protein and is closely related to the critical, ultimate toxic and genotoxic metabolite. The target dose as measured by hemoglobin adducts in erythrocytes reflects not only the actual uptake from the environment but also an individual's capacity for metabolic activation and is therefore an improved dosimeter for human exposure. The usefulness of hemoglobin adducts in molecular epidemiology is now widely recognized. With regard to risk assessment, many questions need to be answered. The described experiments in rats address some of these questions. The relationship between binding to hemoglobin in erythrocytes and to proteins in plasma has been found to vary considerably for a number of diamines. The fraction of hydrolyzable adducts out of the total protein adducts formed also varies in both compartments. This indicates that the kind of circulating metabolites and their availability in different compartments is compound specific. This has to do with the complex pattern of competing metabolic pathways, and the role of N-acetylation and deacetylation is emphasized. An example of nonlinear dose dependence adds to the complexity. Analysis of hemoglobin adducts reveals interesting insights into prevailing pathways, which not only apply to the chemical, but may also be useful to assess an individual's metabolic properties. In addition, it is demonstrated that the greater part of erythrocytes and benzidine-hemoglobin adducts are eliminated randomly in rats, i.e., following first-order kinetics.

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Section: Elimination Of Hemoglobin Adductsmentioning

confidence: 99%

Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

Neumann

Birner

Kowallik

et al. 1993

Environ Health Perspect

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The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats

Álvarez-Guerra

Nazaret²,

Garay³

1998

Journal of Hypertension

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When fed a low-salt diet, Dahl salt-sensitive rats present slightly increased plasma CIF levels and normal erythrocyte cotransport fluxes under basal conditions, but an increased response to a hypertonic shock. Therefore, if there is any primary cotransport abnormality in Dahl salt-sensitive rats, it appears to be restricted to the renal Na,K,Cl cotransporter BSC1 isoform. Alternatively, any such change may be the consequence of abnormal regulation by osmolarity-dependent mechanisms.

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Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

Garay

Álvarez-Guerra

Alda

et al. 1998

Clinical and Experimental Hypertension

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A furosemide-sensitive Na-K-Cl cotransporter (NKCC2 isoform) accounts for almost all luminal NaCl reabsorption in the thick ascending limb of Henle's loop (TALH). The activity of this transport protein is regulated by humoral factors (CIF: cotransport inhibitory factors). One family of CIF compounds is represented by the urinary phytoestrogens equol and genistein, which inhibit cotransport fluxes at similar concentrations as furosemide. Moreover, they possess similar salidiuretic potency as furosemide in the isolated perfused rat kidney, but are less potent than furosemide in vivo. Thus, dietary phytoestrogens can be responsible, at least in part, for the low blood pressure of vegetarians. A second type of CIF is represented by a circulating and urinary factor which is evoked by salt-loading. This, which is not a "ouabain-like" factor, appears to be a new retropituitary natriuretic compound. Endogenous CIF is increased in hypertensive Dahl salt-sensitive rats, probably as a compensatory mechanism against the enhanced NaCl reabsorption in the TALH, which characterizes this model of hypertension. Finally, chronic excess of circulating CIF inhibits and induces up-regulation of erythrocyte Na-K-Cl cotransporter NKCC1.

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Effects of malotilate on rat erythrocytes.

Abstract: Abstract-Rats developed anemia during treatment with high doses of malotilate, a hepatotropic agent. A repeated dose of 1,000 mg/kg caused a 20-30% decrease

Cited by 3 publications

References 19 publications

Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

Hemoglobin adducts of N-substituted aryl compounds in exposure control and risk assessment.

The erythrocyte Na,K,Cl cotransporter and its circulating inhibitor in Dahl salt-sensitive rats

Regulation of Renal Na-K-Cl Cotransporter NKCC2 by Humoral Natriuretic Factors: Relevance in Hypertension

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