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At least 19 recordsLinked to original sources

PubMed1978

Influence of glomerular filtration rate on renal PAH secretion rate in the rat kidney. Dependency of PAH extraction on renal filtration fraction.

PAH secretion (TPAH) was studied in rats at spontaneously occurring glomerular filtration rate (GFR). At saturated transport, TPAH was found to be correlated to GFR. This relationship was also observed at unsaturated transport where TPAH depends upon the PAH concentration in arterial plasma. However, no significant correlation between TPAH and renal PAH load or renal plasma flow rate was found when the effects of GFR were removed by partial correlation analysis. A dependency of TPAH on GFR explains the correlations found between filtration fraction (FF) and renal PAH extraction (EPAH) or renal tubular PAH extraction fraction (EPAH--FFPAH). Thus, even at low PAH concentration in a. plasma, renal PAH extraction may only be assumed to be constant if the filtration fraction is constant.

Aminohippuric Acids↗

PubMed1992

Polycyclic aromatic hydrocarbon (PAH) ortho-quinone conjugate chemistry: kinetics of thiol addition to PAH ortho-quinones and structures of thioether adducts of naphthalene-1,2-dione.

Polycyclic aromatic hydrocarbon (PAH) o-quinones are products of an NADP+ dependent oxidation of non-K-region trans-dihydrodiols catalyzed by dihydrodiol dehydrogenase (EC 1.3.1.20). Since these PAH o-quinones could be detoxified by non-enzymatic or enzymatic conjugation with cellular thiols, their reactivity with 2-mercaptoethanol, cysteine and glutathione (GSH) was examined by ion-pair reverse phase high pressure liquid chromatography (RP-HPLC). Second-order rate constants for the addition of these thiols to naphthalene-1,2-dione (NPQ) in water ranging from 4.9 x 10(3) - 1.1 x 10(4) min-1 M-1 and the reactions were complete within 10 min. When these reactions were conducted at near physiological pH (50 mM potassium phosphate buffer pH 7.0), the rate constants increased by 2-orders of magnitude. When benzo[a]pyrene-7,8-dione (BPQ) was substituted in these reactions the second-order rate constants decreased by 2-3 orders of magnitude and the reactions took several hours to reach completion. The decrease in reactivity can be explained by the presence of the bay region in BPQ. Methylation influenced the reactivity of PAH o-quinones with GSH and the following order of reactivity was observed: 7,12-dimethyl-benz[a]anthracene-3,4-dione (7,12-DMBAQ) >> 12-methyl-BAQ, 7-methyl-BAQ and BAQ >> BPQ. Of these quinones 7,12-dimethyl-BAQ was almost equi-reactive with NPQ. This suggests that methyl substitution in the bay and peri regions enhances reactivity with GSH. Using NPQ as a model for other PAH o-quinones, N-acetyl-L-cysteine, L-cysteine and GSH conjugates of NPQ were synthesized and characterized by [1H]- and [13C]NMR. Evidence for Michael type 1,4-addition products was obtained in which the resultant adduct could exist as either a catechol or o-quinone. By contrast, L-cysteine was able to form adducts via S- or N-attack and N-attack gave a purple p-iminoquinone. There was no evidence for the formation of bis-N-acetyl-L-cysteinyl-, bis-glutathionyl adducts or phenolic coupled products. The toxicity of thiol conjugates of NPQ remains to be explored.

Benzopyrenes↗

PubMed1976

PAH clearance, sodium excretion, and PAH extraction ratio in acidotic near-term lambs treated with hypertonic sodium bicarbonate.

The electrolyte changes and renal hemodynamic adjustment to hypertonic sodium bicarbonate (NaHCO3) correction of a metabolic acidosis were studied in 4 neonatal lambs and in 2 controls. PAH clearance increased from 0.92 to 1.65 ml/min/kg (p less than 0.05), urine flow from 0.37 to 0.61 ml/min/kg (p less than 0.05), and Na excretion from 8.4 to 23.7 muEq/min/kg (p less than 0.05) during the NaHCO3 infusion. These increases were transient and returned to pre-infusion levels following NaHCO3 infusion. Calculation of Na intake and output revealed a net retention of 5.1 mEq/kg in the study lambs which was reflected in a rise of serum Na and osmolarity (Osm) during the post-NaHCO3 -infusion period. The extraction ratio of sodium p-aminohippurate (EPAH) and its relationship to arterial pH were studied in 4 additional lambs. The EPAH did not change with metabolic acidosis but for unknown reasons, the infusion of NaHCO3 resulted in a temporary depression of EPAH (p less than 0.001).

Acidosis↗

PubMed1979

Postnatal development of renal function in piglets: glomerular filtration rate, clearance of PAH and PAH extraction.

Glomerular filtration rate (GFR), estimated as clearance of inulin, and clearance of p-aminohippuric acid (CPAH) were measured in 32 unanaesthetized piglets 1--62 days of age. During this period of time, GFR increased from 0.27 to 0.59 ml/min/g kidney and CPAH increased from 1.02 to 1.72 ml/min/g kidney. At 8 weeks of age, GFR and CPAH equaled adult values. In addition, renal PAH extraction (EPAH) was estimated in 12 anaesthetized piglets aged 1--79 days. EPAH increased from 0.75 at birth to 0.86 (adult value) at 3 weeks of age. The result shows a postnatal increase in renal functions in piglets, but the development from birth to adult level was less pronounced than seen in other animal species.

Animals↗

PubMed1992

PAH/alpha-KG countertransport stimulates PAH uptake and net secretion in isolated rabbit renal tubules.

Possible stimulation of both basolateral uptake and net transepithelial secretion of p-aminohippurate (PAH) by PAH/alpha-ketoglutarate (alpha-KG) countertransport was examined in intact perfused and nonperfused rabbit proximal S2 renal tubules. Preloading tubules with alpha-KG (100 microM) for 30 min increased [14C]-PAH rate of uptake by nonperfused tubules and rate of net secretion by perfused tubules approximately three- to sixfold. During stimulation of net secretion, intracellular [14C]PAH concentration increased to about the same extent as net secretion. Presence of Li+ (2 mM) or absence of Na+ (inhibitors of Na(+)-dicarboxylate cotransport) in bathing medium during alpha-KG preloading eliminated stimulation of PAH transport. Addition of unlabeled alpha-KG (1 mM) to bathing medium stimulated efflux of [14C]PAH across the basolateral membrane of tubules with oil-filled lumina, further supporting the concept of PAH/alpha-KG countertransport. Preloading with succinate (100 microM) also stimulated rates of [14C]PAH uptake by nonperfused tubules and net secretion by perfused tubules, but stimulation was only approximately 1.5-fold. Moreover, preloading with methyl succinate, a slowly metabolized derivative of succinate, did not stimulate [14C]PAH uptake by nonperfused tubules or net secretion by perfused tubules. Thus it seems most likely that succinate preloading stimulates PAH transport via metabolism, possibly by conversion to alpha-KG, not by direct countertransport for PAH. This study indicates for the first time in intact mammalian proximal S2 renal tubules that PAH/alpha-KG countertransport can stimulate net PAH secretion by generating an increased intracellular PAH concentration.

Animals↗

PubMed1992

Adsorption of polycyclic aromatic hydrocarbons (PAHs) by soil particles: influence on biodegradability and biotoxicity.

Polycyclic aromatic hydrocarbon (PAH) biodegradation was investigated in contaminated soils from two different industrial sites under simulated land treatment conditions. Soil samples from a former impregnation plant (soil A) showed high degradation rates of PAHs by the autochthonous microorganisms, whereas PAHs in material of a closed-down coking plant (soil B) were not degraded even after inoculation with bacteria known to effectively degrade PAHs. As rapid PAH biodegradation in soil B was observed after PAHs were extracted and restored into the extracted soil material, the kind of PAH binding in soil B appears to completely prevent biodegradation. Sorption of PAHs onto extracted material of soil B follows a two-phase process (fast and slow); the latter is discussed in terms of migration of PAHs into soil organic matter, representing less accessible sites within the soil matrix. Such sorbed PAHs are suggested to be non-bioavailable and thus non-biodegradable. By eluting soil B with water, no biotoxicity, assayed as inhibition of bioluminescence, was detected in the aqueous phase. When treating soil A analogously, a distinct toxicity was observed, which was reduced relative to the amount of activated carbon added to the soil material. The data suggest that sorption of organic pollutants onto soil organic matter significantly affects biodegradability as well as biotoxicity.

Adsorption↗

PubMed1976

PAH transport and fluid absorption by isolated perfused frog proximal renal tubules.

Para-aminohippurate (PAH) transport and fluid absorption were studied in isolated perfused frog (Rana catesbeiana) proximal renal tubules. With 2 X 10(-5) M PAH in the bath, tubule fluid-to-bath (TF/B) concentration ratios averaged 3.0 and net secretion averaged 746 X 10(-15) mol min(-1) mm(-1) in the proximal tubule. Net PAH secretion did not vary with perfusion rate. During PAH secretion, cell water PAH concentration exceeded that in the tubular fluid or bath, suggesting active transport into cells and subsequent diffusion into lumen. In accordance with this concept, luminal membrane permeability (3.8 X 10(-5) cm s(-1) calculated from perfusion studies was about 6 times greater than peritubular membrane permeability (0.66 X 10(-5) cm s(-1)) determined from studies of PAH efflux from tubules with oil-filled lumens. Net transepithelial PAH transport saturated at bath concentration of about 6 X 10(-5) M. Addition of 20 mM urea to PAH bath concentration of 2 X 10(-5) M reduced net PAH secretion by 32%. Fluid absorption in proximal tubules averaged 0.34 nl min(-1) mm(-1). Ouabain (10(-4), 10(-5), or 10(-6) M) added to bath blocked fluid absorption. Fluid absorption was partially restored following removal of ouabain.

Acetates↗

PubMed1979

Relationship between PAH transport and Na-K-ATPase activity in the rabbit kidney.

The relationship between Na-K-ATPase activity and p-aminohippurate (PAH) transport was examined in renal cortical slices of mixed-breed rabbits by using ouabain to vary the level of Na-K-ATPase activity. Ouabain increased passive PAH uptake, measured in the presence of probenecid. Slice homogenate Na-K-ATPase activity was inhibited by 50% with about 2 X 10(-6) M ouabain. When the concentration was 10(-5) M or above, active PAH uptake was inhibited. Lower concentrations (10(-7) and 10(-6) M) of ouabain stimulated active PAH uptake. Acetate stimulated PAH uptake when medium ouabain was less than 10(-4) M. Ouabain, 10(-5) M and higher, caused intracellular K+ to fall and Na+ to rise. The changes in active PAH uptake observed with ouabain correlated much better with changes in intracellular K+ or Na+ levels (P less than 0.01) than with changes in slice homogenate Na-K-ATPase activity. Vmax for active PAH uptake decreased with 5 X 10(-5) M ouabain, and tended to increase with 10(-7) M ouabain. Ouabain did not alter Km for active PAH uptake. The data support the hypothesis that there is a functional link between active PAH transport and Na-K-ATPase activity. This linkage may be an indirect one mediated by changes in intracellular cation concentrations.

Aminohippuric Acids↗

PubMed2026

Pollution characteristics and health risks of PAHs and OPAHs in PM2.5 of an inland basin city in China under the influence of the clean air action plan.

Since the implementation of China's Clean Air Action, remarkable progress has been made in air pollution control, with continuous air quality improvement in Xi'an, a typical inland basin city in the Fenwei Plain. To clarify winter organic aerosol pollution variations and pinpoint targeted control needs under policy regulation, this study investigated PM2.5-bound polycyclic aromatic hydrocarbons (PAHs) and oxygenated derivatives (OPAHs) in winter Xi'an, focusing on pollution levels, chemical compositions, source contributions, meteorological impacts, regional transport and health risks. Historical comparison showed generally lower wintertime PAH concentrations in Xi'an during the period of China's clean-air actions. PMF results indicated mixed source influences on PAHs and OPAHs, with biomass-burning-related mixed combustion showing the largest contribution. During haze episodes, absolute concentrations of both PAHs and OPAHs increased; the increase was statistically significant for OPAHs but not for parent PAHs, while 4-5 ring PAHs and BcdPQ dominated the PAH and OPAH profiles, respectively. Meteorological variability, particularly synoptic pressure patterns, was strongly associated with pollutant concentrations, and regional pollution was dominated by in-basin accumulation combined with short-range transport from northern Shaanxi industrial zones. Haze periods exhibited higher toxic-equivalent concentrations, with OPAHs, particularly BcdPQ, dominating the toxicity-equivalent burden. Screening-level ILCR estimates generally remained below 10⁻4 but increased during haze episodes, especially for adult and elderly groups. In conclusion, China's clean air actions have coincided with lower wintertime PAH pollution, but stronger control of residential biomass and other solid-fuel combustion, traffic emissions, and OPAH formation remains necessary in the Fenwei Plain.

China↗

PubMed1976

Low Na+ effects on PAH transport and permeabilities in isolated snake renal tubules.

Effects of low sodium concentrations on p-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Replacement of sodium in bath with choline led to significant depression of net PAH transport from bath to lumen in less than 10 min and to maximum depression (to 25-30% of control) in about 30 min, but transport still occurred against concentration gradient. In absence of sodium, PAH concentration in cell water was markedly depressed, but was still slightly greater than that in bath or lumen. Apparent permeability of peritubular membrane, determined from PAH efflux from tubules with oil-filled lumens, averaged about 0.5 X 10(-5) cm s-1 in 150 mM sodium and about 1.1 X 10(-5) cm s-1 in sodium-free medium. Data suggest that both decreased rate of active transport and increased apparent permeability of peritubular membrane contribute to depression of net transepithelial PAH transport and cell water PAH concentration in sodium-free medium. When sodium was restored to bath, net PAH transport nearly tripled in 15 min. Reduction of bath sodium concentration to one-half control or perfusion with sodium-free medium in lumen and control medium in bath had no effect on net PAH transport.

Aminohippuric Acids↗

PubMed1978

Effects of renal fuels on uptake of PAH and uric acid by separated renal tubules of the rabbit.

A rapid-filtration procedure was used to examine the effects of a wide variety of renal fuels on the uptake of p-aminohippuric acid (PAH) and uric acid (UA) by separated rabbit renal tubules. PAH and UA uptakes in 15 min over a range of substrate concentrations of 0.01-10.2 mM were determined. All tricarboxylic acid cycle intermediates and pyruvate showed biphasic stimulation of PAH and UA uptake. alpha-Ketoglutarate produced a 320 +/- 54% increase in PAH uptake and a 192 +/- 60% increase in UA uptake at 0.16 mM, the concentration at which uptake was maximal, while causing 20 +/- 3 (PAH) and 35 +/- 7% (UA) inhibition at 10.2 mM. Citrate produced a 373 +/- 19% increase in PAH uptake and a 246 +/- 41% increase in UA uptake at 0.64 mM. PAH and UA uptake were also stimulated by acetate, glucose frutose, phosphoenolypyruvate and L-glutamic acid. The data indicate a direct relationship between stimulation of PAH and uric acid transport and stimulation of renal cortical oxidative metabolism.

Aminohippuric Acids↗

PubMed1979

Effects of inhibitors in lumen on PAH and urate transport by isolated renal tubules.

Effects of the presence of unlabeled p-aminohippurate (PAH) or urate, probenecid, and phenol red in the lumen on labeled PAH or urate transport by isolated, perfused snake (Thamnophis spp.) proximal renal tubules were studied. Net secretion of labeled urate and luminal membrane permeability to urate were unaffected by the presence of unlabeled urate (up to 0.1 mM) or probenecid (up to 1.0 mM) in lumen only. The data are compatible with movement of urate from cells to lumen during urate secretion by a simple passive process. Net secretion of labeled PAH was rapidly and reversibly depressed to about 25-35% of control when unlabeled PAH (0.05 mM), phenol red (0.05 mM), or probenecid (0.1 mM) was added to the lumen only. During maximum depression of PAH transport, luminal membrane permeability to PAH was reduced by 60-70%. The data suggest that movement of PAH from cells to lumen down an electrochemical gradient during PAH secretion occurs by a readily inhibited, mediated process.

Animals↗

PubMed1978

Alteration of renal cortical palmitate utilization and p-aminohippurate (PAH) accumulation after penicillin treatment of neonatal rabbits.

The renal organic anion transport system has been linked to the selective extraction of nonesterified fatty acids (NEFA) from arterial blood. Consequently, p-aminohippurate (PAH) and palmitate may compete for a common intracellular binding site or may be handled by a common enzymatic pathway. The purpose of this study was to identify sites of interaction by correlating alterations in PAH accumulation and palmitate metabolism after selective stimulation of the PAH transport system. Penicillin treatment of immature rabbits increased PAH accumulation by suspensions of proximal tubules prepared nonenzymatically) and altered distribation of incorporated palmitate[14C] within tubule lipid classes. Penicillin increased palmitate[14C] esterified to triglycerides and decreased 14C recovered as NEFA. Administration of iodipamide had no effect on PAH accumulation and did not alter palmitate utilization. Penicillin treatment of mature rabbits did not alter either tubule PAH accumulation or palmitate esterification. These results suggested that palmitate and PAH share a common intracellular binding site and that penicillin enhanced PAH accumulation by removing endogenous inhibitors (NEFA).

Aging↗

PubMed1992

Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs).

The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are commonly encountered at hazardous waste sites and are often the focus of site remediation activities. However, toxicity criteria are not available for all the PAHs. In the past, EPA has assessed risks posed by mixtures of PAHs by assuming that all carcinogenic PAHs are as potent as benzo[a]pyrene (B[a]P), one of the most potent PAHs. The available information on the toxicity of the PAHs suggests that most are considerably less potent than B[a]P and therefore, the EPA approach is likely to overestimate risks. Several approaches have been developed to allow the relative potency of the different PAHs to be considered in a site-specific risk assessment. This paper evaluates these approaches and presents a modified version that we feel more accurately reflects the state of knowledge on the relative potency of these compounds.

Animals↗

PubMed1975

High K+ effects on PAH transport and permeabilities in isolated snake renal tubules.

Effects of high potassium concentrations on para-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Increasing the potassium concentration in bath from 3 mM TO 10 mM OR 40 MM led to about 50% decrease in net PAH transport from bath to lumen in less than 10 min, but transport still occurred against concentration gradient. Cell water PAH concentration was not significantly depressed in 10 mMpotassium and was nearly double control level in 40 mM potassium. Apparent luminal membrane permeability to PAH, calculated from perfusion studies, averaged about 3.5 x 10(-5) cm sec(-1) in 3 mM potassium, 1.15 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.48 x 10(-5) cm sec(-1) in 40 mM potassium. Apparent peritubular membrane permeability, determined from PAH efflux from tubules with oil-filled lumens averaged about 0.5 x 10(-5) cm sec(-1) in 3 mM potassium, 0.29 x 10(-5) cm sec(-1) in 10 mM potassium, and 0.17 x 10(-5) cm sec(-1) in 40 mM potassium. These data suggest that high potassium concentrations depress transepithelial PAH transport primarily by reducing luminal and peritubular membrane permeabilities. Effect of high potassium on PAH transport was reversed within 20 min after restoration of control potassium concentration.

Aminohippuric Acids↗

PubMed1979

Spin transition of camphor-bound cytochrome P-450. 2. Kinetics following rapid changes of the local paH at sub-zero temperatures.

The kinetics of the spin transition in the heme iron of the cytochrome P-450 substrate complex have been observed by stopped-flow measurements between 4 degrees C and -27 degrees C. Large displacements in the spin equilibrium are induced by small changes in the concentration of hydrogen or potassium ions. The kinetic and thermodynamic data indicate that the spin transition is rate-limited by conformational changes of the protein. The spin transition appears to be governed by the local paH, modulated in turn by external factors: a satisfying kinetic analysis is attained only by accounting for the difference between local paH (paH, in) and bulk paH (paH, out), as described in the preceding paper. Indeed, the low-spin to high-spin rate constant obeys a local paH titration curve with a pK = 5.4 +/- 0.1 at -17 degrees C.

Camphor↗

PubMed1976

Effects of azotemia on renal extraction and clearance of PAH and TEA.

Dogs were made azotemic by bilateral ureteral-venous anastomosis. Subsequently, the left ureter, a systemic artery, and the left renal vein were cannulated. Left renal blood flow (RBF) was measured by an electromagnetic flowmeter. Left renal clearances and extractions of [14C]tetraethylammonium ([14C]TEA) and p-aminohippuric acid (PAH) were determined at five 40-min intervals after administraiton of loading doses and institution of a maintenance infusion containing PAH and [14C]TEA. The renal extraction of TEA was independent of blood urea nitrogen (BUN), whereas the extraction of PAH correlated inversely with BUN. Renal plasma flows calculated from urinary clearances and renal extractions agreed with renal plasma flows calculated from flowmeter data. The extraction of TEA remained constant over the 200-min experimental period, whereas the extraction of PAH increases progressively as a function of time. It is probable that those organic acids which accumulate in azotemia, and interfered with renal tubular secretion of PAH, were themselves eliminated after opening the ureteral-venous anastomosis. Thus, TEA is superior to PAH for evaluation of the renal circulation in azotemia.

Aminohippuric Acids↗

PubMed1978

Concentrative PAH transport by rabbit kidney slices in the absence of metabolic energy.

Characteristics of para-aminohippurate (PAH) transport in the absence of intracellular metabolism were studied with Na+, K+-depleted and ouabain-poisoned rabbit kidney cortex slices. The imposition of a NaCl gradient (out to in) resulted in specific stimulation of PAH uptake. PAH accumulated against its concentration gradient when cell [Na+] was less than medium [Na+]. Conversely, renal cells extruded PAH when cell [Na+] exceeded medium [Na+]. Membrane potential measured with triphenylmethylphosphonium revealed that conditions which created an interior-positive membrane potential inhibited the Na+-dependent transport of PAH but caused stimulation of the Na+-independent component. Characteristics of the Na+-dependent PAH transport system in ouabain-poisoned slices were similar to those previously described in metabolically active tissues.

Aminohippuric Acids↗