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F J Koschier

Publications and source records attributed to F J Koschier.

23 records · Page 2Linked to original sources

Studies on the mechanism of renal transport depression caused by pretreatment with 2,4,5-trichlorophenoxyacetate.

Relatively low toxicity in the adult has been reported for the organic acid herbicides 2,4-dichlorophenoxyacetate and 2,4,5-trichlorophenoxyacetate (2,4,5-T). Although small doses of these herbicides are excreted rapidly, acute impairment of renal excretion has been reported when large doses of herbicide were administered. After the administration of 2,4,5-T in vitro analysis of renal proximal tubular function showed a decrease in the activity of the organic acid transport system which handles these herbicides. In addition, the pretreated animals show an impairment in the organic base transport system. To determine the nature of 2,4,5-T renal depression, renal cortical slices from herbicide-pretreated animals were studied. Alterations in the initial influx of organic ions, steady-state accumulation, and efflux were measured. Furthermore, a specific and reversible depression of tissue oxygen consumption was demonstrated. These changes do not appear to be the result of alterations in the gross morphology, electrolyte composition, or cell water content of the renal cortex.

2,4,5-Trichlorophenoxyacetic Acid↗

Renal transport and renal metabolism of 2, 4, 5-trichlorophenoxyacetate by the chicken.

In vitro and in vivo renal tubular transport of 2,4,5-trichlorophenoxyacetate (2,4,5-T), a hormone-type herbicide, was studied in the chicken. Renal cortical slices incubated with 14C-labeled 2,4,5-T demonstrated a slice-to-medium ratio of the 14C-label of 26 after 2 hr of incubation. This accumulation was inhibited significantly by probenecid, phenol red, dinitrophenol and iodoacetamide. In vitro metabolism of 2,4,5-T was apparent in the renal slice studies; at least two metabolites were found by electrophoretic analysis. Even though chicken liver slices were able to accumulate 2,4,5-T, the accumulated herbicide was not metabolized. In addition, chicken kidney slices metabolized 2,4,5-T to a much greater extent than did rat or rabbit kidney slices, which produced only negligible amounts of metabolites. When [14C]-2,4,5-T was infused into the renal portal system of the chicken, the 14C-label originally associated with 2,4,5-T was shown to be secreted by the renal tubule. Probenecid inhibited the transport of the 14C-label without affecting the simultaneous transport of tetra-ethylammonium, an organic cation transported by the renal proximal tubule. At the present infusion rate of 2,4,5-T (2.9 X 10(-10) mol/min), the excreted label was associated primarily with an acidic metabolite(s). It can be concluded that the chicken transports 2,4,5-T by a probenecid sensitive mechanism; however, this transport appears to be associated with the metabolism of the herbicide.

2,4,5-Trichlorophenoxyacetic Acid↗

Renal tubular transport and nephrotoxicity of DDA.

Since DDA [bis(p-chlorophenyl)acetic acid] has been shown to be transported and concentrated by the renal proximal tubule, this metabolite of DDT has been postulated to be a potential nephrotoxic agent. The present study explored the renal transport of DDA in the isolated, perfused rat kidney and the effects of DDA on renal function. When DDA (0.6 microM) was present in a dextran perfusate which eliminated DDA-colloid binding, the DDA/inulin clearance ratio was congruent to 0.05; however, some metabolism of DDA was apparent. During these studies, DDA had no effect on the glomerular filtration rate and the fractional reabsorption of Na, K or H2O. To determine the concentration of DDA which would produce an effect on renal cellular function, studies were performed with renal cortical slices. DDA at media concentrations greater than or equal to 0.1 mM were needed to produce significant alterations in tetraethylammonium transport, tissue oxygen consumption and intracellular electrolyte composition; however, no effect was demonstrated on Na-K-ATPase activity although DDA did affect Mg-ATPase activity. In conclusion, DDA at a 0.6 microM perfusate concentration undergoes net tubular reabsorption and metabolism without affecting the function of the perfused kidney. Only high concentrations of DDA were shown to produce alterations in cellular function.

Adenosine Triphosphatases↗