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Biomedical subjects

D J Yang

Publications and source records attributed to D J Yang.

At least 91 records · Page 5Linked to original sources
PubMed1987

Role of glutathione in acute N-(3,5-dichlorophenyl) succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer 344 rats.

N-(3,5-Dichlorophenyl)succinimide (NDPS), an experimental agricultural fungicide, has been shown to be a selective nephrotoxin in Sprague-Dawley and Fischer 344 rats. Previous studies have demonstrated that a toxic metabolite contributes to or is responsible for acute NDPS-induced nephrotoxicity. The purpose of this study was to investigate the role of glutathione in NDPS-induced renal effects. In 1 set of experiments, male Sprague-Dawley or Fischer 344 rats received a single intraperitoneal (i.p.) injection of NDPS (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg). Rats were killed at 1, 3, 6 or 24 h, and reduced (GSH) and oxidized (GSSG) glutathione concentrations determined in liver and renal cortex. In both rat strains NDPS (0.4 or 1.0 mmol/kg) administration produced small decreases in GSH concentrations (1 and 3 h) but moderate increases in GSSG concentrations (1 and 3 h) in liver and kidney. At 24 h both GSH and GSSG concentrations were increased, particularly in kidney. In a second set of experiments, rats were pretreated with the glutathione depletor diethyl maleate (DEM) (0.4 ml/kg, i.p.) 1 h prior to NDPS (0.2, 0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.) administration, and renal function monitored at 24 and 48 h. DEM pretreatment attenuated the increase in urine volume (24 and 48 h), proteinuria, glucosuria, hematuria and elevated blood urea nitrogen (BUN) concentration produced by NDPS (0.4 or 1.0 mmol/kg) in both Sprague-Dawley and Fischer 344 rats. NDPS-induced increases in kidney weight also were generally prevented by DEM pretreatment. Proximal tubular necrosis produced by NDPS administration was reduced by DEM but not prevented. Pretreatment with the cysteine conjugate beta-lyase inhibitor amino-oxyacetic acid (0.5 mmol/kg, i.p.) 1 h prior to NDPS (0.4 or 1.0 mmol/kg) markedly attenuated all NDPS-induced effects on renal function and morphology. These results suggest that glutathione does not play a protective role against NDPS-induced renal effects and that a glutathione or cysteine conjugate of NDPS might contribute to NDPS-induced nephrotoxicity.

Aminooxyacetic Acid↗
PubMed1987

The effect of probenecid on acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in the Fischer 344 rat.

N-(3,5-Dichlorophenyl)succinimide (NDPS), an experimental agricultural fungicide, has been shown to produce selective nephrotoxicity in rats. Previous studies have shown that a metabolite(s) of extrarenal origin contributes to acute NDPS-induced nephrotoxicity. The purpose of this study was to determine if the organic acid transport inhibitor probenecid could modify the renal toxicity produced by NDPS administration. Male Fischer 344 rats were administered a single intraperitoneal (i.p.) injection of probenecid (60, 90 and 120 mg/kg) or 0.9% saline (1.0 ml/kg) followed 30 min later by NDPS (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.) Renal function was monitored at 24 h and 48 h. Probenecid (60 mg/kg) did not markedly alter NDPS-induced renal effects on either post-treatment day. However, pretreatment with probenecid (90 or 120 mg/kg) blocked or attenuated the diuresis, increased proteinuria, decreased tetraethylammonium (TEA), uptake, elevation in blood urea nitrogen (BUN) concentration and increased kidney weight produced by NDPS (0.4 mmol/kg) administration. Only increased kidney weight and BUN concentration, and decreased lactate-stimulated p-aminohippurate (PAH) uptake were altered by probenecid (120 mg/kg) pretreatment when NDPS (1.0 mmol/kg) was given. NDPS-induced changes in renal morphology were not prevented by pretreatment with any probenecid dose. These results suggest that at least one nephrotoxic metabolite of NDPS is an organic acid. However, this acidic metabolite might not be the major nephrotoxic metabolite or a precursor to the major nephrotoxic metabolite(s). The identity of these metabolites remains to be determined.

Animals↗
PubMed1987

Acetone effects on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity.

Acetone has been shown to potentiate the toxicity of many halogenated hydrocarbons. The purpose of this study was to determine if acetone could alter the acute nephrotoxicity produced by the experimental fungicide N-(3,5-dichlorophenyl)succinimide (NDPS). Male Fischer 344 rats were administered acetone (1, 5 or 10 mmol/kg) or acetone vehicle (corn oil, 10 mg/kg) orally followed 16 h later by a single intraperitoneal injection of NDPS (0.2 or 0.4 mmol/kg) or NDPS vehicle (sesame oil, 2.5 ml/kg) and renal function was monitored at 24 and 48 h. Acetone (1 or 5 mmol/kg) did not alter NDPS (0.2 mmol/kg)-induced renal effects while acetone (10 mmol/kg) pretreatment attenuated NDPS (0.4 mmol/kg)-induced increases in blood urea nitrogen (BUN) concentration and kidney weight but had no effect on NDPS (0.4 mol/kg)-induced changes in urine volume or content, organic ion accumulation by renal cortical slices or renal morphology. These results suggest that acetone weakly attenuates NDPS-induced nephrotoxicity.

Acetone↗
PubMed1987

Nephrotoxicity of N-(3,5-dihalophenyl)succinimides in Fischer 344 rats.

Previous studies have demonstrated that N-(3,5-dichlorophenyl)succinimide (NDCPS) is the most nephrotoxic compound among the N-(mono- or dichlorophenyl)succinimides. The purpose of this study was to examine the nephrotoxic potential of the different N-(3,5-dihalophenyl)succinimides (NDHPS) to determine the importance of the halogen species for NDHPS-induced nephrotoxicity. Male Fischer 344 rats were administered a single intraperitoneal injection of an NDHPS (0.4, 0.8, or 1.0 mmol/kg) or vehicle (2.5 ml/kg), and renal function was monitored at 24 and 48 h. NDCPS or N-(3,5-diiodophenyl)succinimide administration produced the greatest nephrotoxic response. Nephrotoxicity was characterized by diuresis, increased proteinuria, glucosuria, increased kidney weight and blood urea nitrogen (BUN) concentration, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA) by renal cortical slices and proximal tubular necrosis. N-(3,5-Dibromophenyl)succinimide injection produced mild nephrotoxicity, while N-(3,5,-difluorophenyl)succinimide administration did not result in nephrotoxicity. These results indicate that the halogen species can influence the nephrotoxicity produced by the NDHPS. In addition, nephrotoxic potential did not correlate with fungicidal efficacy, which suggests that the nephrotoxic and fungicidal mechanisms of these compounds might be different.

Animals↗
PubMed1987

Erythrocyte sedimentation rate and C-reactive protein values in patients with total hip arthroplasty.

Serum C-reactive protein (CRP) levels and erythrocyte sedimentation rates (ESR) were measured serially in 50 osteoarthritic patients treated with uncomplicated primary total hip arthroplasties (THAs) and also in 28 patients with painful hip for different periods after THA. The follow-up period was one year. In uncomplicated primary THA, the ESR was slightly elevated before surgery and was variable after surgery; some patients continued to have abnormally high ESRs one year after surgery. However, CRP was normal before surgery and after surgery showed a distinctive pattern that rapidly normalized within three weeks. In patients with a painful hip after THA, ESR was elevated in those with septic loosening and variable in those with mechanical loosening; however, the difference was not significant. ESR after successful revision THA was also variable. CRP was high in patients with septic loosening and normal in those with mechanical loosening. Normalization of CRP was rapid after control of infection or within three weeks of successful revision THA. Uneventful recovery after THA is indicated by normalization of CRP within three weeks, regardless of ESR. Measurement of both ESR and CRP is helpful in differentiating septic and mechanical loosening, detecting complications, and monitoring the effects of treatment, but CRP is more informative and sensitive than ESR for these purposes.

Adult↗
PubMed1987

Computed tomography of a meniscal cyst.

A meniscal cyst of the knee is a rare lesion, and a palpable large meniscal cyst is even more rare. This article suggests that CT scan demonstrates clear location, size, contents, and connection of the cyst with meniscus and peripheral tissue. By a combination of arthrography and CT scan, detection of the cysts in zone 3 (parameniscal area) is possible with ample demonstration of whether the cyst is associated with a meniscal tear. This provides a guideline in determining the treatment of the lesion.

Adult↗
PubMed1986

Deuterium isotope effect in acute N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity.

Deuterium labelling of the succinimide ring of N-(3,5-dichlorophenyl) succinimide (NDPS) markedly reduced the acute nephrotoxicity produced by NDPS administration to Fischer 344 rats. Administration of the deuterium-labelled derivative, NDPS-d4, to male Fischer 344 rats failed to produce the marked diuresis, increased proteinuria, glucosuria, hematuria, elevated blood urea nitrogen (BUN) concentration and kidney weight, decreased basal p-aminohippurate (PAH) accumulation, and proximal tubular necrosis which are characteristic of NDPS-induced nephrotoxicity. However, lactate-stimulated PAH and tetraethylammonium (TEA) accumulation were decreased by NDPS-d4 (1.0 mmol/kg). The lack of nephrotoxicity produced by NDPS-d4 suggests that oxidation at the carbon-carbon bridge of the succinimide ring is an important biotransformation step in the generation of the nephrotoxic species of NDPS.

Animals↗
PubMed1986

In vivo and in vitro nephrotoxicity of aniline and its monochlorophenyl derivatives in the Fischer 344 rat.

Aniline (A) and its monochlorophenyl derivatives (2-CA, 3-CA and 4-CA) are widely-used chemical intermediates. In the present study, the in vivo and in vitro nephrotoxic potential of these compounds was assessed in Fischer 344 rats. In the in vivo experiments, rats were administered a single intraperitoneal (i.p.) injection of an aniline (0.4, 1.0 or 1.5 mmol/kg) or 0.9% saline (2.0 ml/kg, i.p.), and renal function monitored at 24 and 48 h. 2-CA was the only compound tested which decreased urine volume, elevated the blood urea nitrogen (BUN) concentration and depressed both basal and lactatestimulated p-aminohippurate (PAH) accumulation by renal cortical slices at the 1.0 mmol/ kg dose. Similar results were produced following 3- and 4-CA administration, but these compounds required a dose of 1.5 mmol/kg. Aniline had little effect on renal function at the doses used in this study. In the in vitro experiments, 2-CA (10(-4) M or greater) depressed basal PAH accumulation. Tetraethylammonium (TEA) uptake was decreased by all compounds with an incubate concentration of the aniline at 10(-3) M. Lactatestimulated PAH uptake was not decreased by any test compound. These results indicate that chlorine substitution on the phenyl ring of aniline enhances nephrotoxic potential, and that 2-substitution produces the greatest increase.

Aniline Compounds↗
PubMed1986

3,5-Dichloroaniline-induced nephrotoxicity in the Sprague-Dawley rat.

The nephrotoxic potential of 3,5-dichloroaniline (DCA) was examined in male Sprague-Dawley rats. Rats were administered DCA (0.4, 0.8 or 1.0 mmol/kg, i.p.), or 0.9% saline (1.0 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. DCA (0.4 mmol/kg) administration did not produce evidence of nephrotoxicity. However, DCA (0.8 mmol/kg) administration decreased urine volume and osmolality, increased proteinuria, elevated the blood urea nitrogen (BUN) concentration and decreased basal and lactate-stimulated p-aminohippurate (PAH) accumulation. Three of 4 rats receiving DCA (1.0 mmol/kg) died prior to 48 h postinjection. Incubation of renal cortical slices with DCA resulted in decreased PAH and tetraethylammonium (TEA) uptake when DCA concentrations of 10(-6) M or greater were used. These results indicate that DCA is nephrotoxic to Sprague-Dawley rats when administered in a dose of 0.8 mmol/kg or higher and is capable of altering organic ion transport in vitro.

Aniline Compounds↗
PubMed1986

Acute N-(3,4,5-trichlorophenyl)succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer-344 rats.

Previous studies have shown that the experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) produces acute nephrotoxicity via a reactive intermediate in Sprague-Dawley and Fischer-344 rats. The purpose of this study was to examine if an arene oxide intermediate is a toxic metabolite contributing to NDPS-induced nephropathy in rats. N-(3,4,5-Trichlorophenyl)succinimide (NTPS) was prepared to prevent arene oxide formation of NDPS, and its nephrotoxic potential was determined in Sprague-Dawley and Fischer-344 rats. Rats were administered a single intraperitoneal injection of NTPS (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and renal function was monitored at 24 and 48 h. NTPS (0.4 or 1.0 mmol/kg) administration produced diuresis, proteinuria, glucosuria, hematuria, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA), and increased blood urea nitrogen (BUN) and kidney weight in both strains. Extensive proximal tubular necrosis was observed in both strains of rat. The magnitude of these effects was similar to those previously reported for NDPS-induced nephrotoxicity in Sprague-Dawley and Fischer-344 rats. It was concluded that an arene oxide metabolite does not contribute to the nephrotoxic potential of NDPS. The results of the present study indicate that lipophilic character alone is not a good predictor of the nephrotoxic potential for NDPS and NTPS.

Animals↗
PubMed1985

Acute nephrotoxicity of N-phenyl and N-(monochlorophenyl) succinimides in Fischer 344 and Sprague-Dawley rats.

The experimental fungicide N-(3,5-dichlorophenyl)succinimide (NDPS) has been shown to be nephrotoxic in Sprague-Dawley and Fischer 344 rats. The purpose of this study was to evaluate the role of the chlorine atoms in NDPS-induced nephropathy. Male Sprague-Dawley or Fischer 344 rats received a single intraperitoneal injection of a phenylsuccinimide (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and renal function was monitored at 24 h and 48 h. In Sprague-Dawley rats urine volume was increased by NDPS and N-(3-chlorophenyl)succinimide (3-NCPS) (0.4 and 1.0 mmol/kg) at 24 h but only by NDPS at 48 h. Accumulation of both p-aminohippurate (PAH) and tetraethylammonium (TEA) was decreased only by NDPS (1.0 mmol/kg) administration. N-(2-chlorophenyl)succinimide (2-NCPS) or N-(4-chlorophenyl) succinimide (4-NCPS) (1.0 mmol/kg) administration reduced only basal and lactate-stimulated PAH accumulation. Only NDPS increased blood urea nitrogen (BUN) concentration and kidney weight. In Fischer 344 rats results were similar to those obtained in Sprague-Dawley rats, except that 3-NCPS was the only monochlorophenylsuccinimide which produced a decrease in PAH accumulation by renal cortical slices. N-Phenylsuccinimide had little effect on any renal parameter studied in either rat strain. The order of increasing nephrotoxicity generally paralleled the increasing partition. coefficients of the compounds. These results indicate that reducing the chlorine substitution of NDPS produces compounds with reduced nephrotoxic potential. In addition, lipophilic character might be a predictor for the nephrotoxic potential of N-(halophenyl)succinimides in Sprague-Dawley and Fischer 344 rats.

Animals↗
PubMed1985

Acute nephrotoxicity of isomeric N-(dichlorophenyl)succinimides in Sprague-Dawley and Fischer 344 rats.

Previous studies have shown that reducing the chlorine content of the experimental agricultural fungicide N-(3,5-dichlorophenyl)succinimide (3,5-NDPS) produces compounds with reduced nephrotoxic potential. The purpose of this study was to determine the importance of the ring position of the two chlorine atoms for the nephrotoxic potential of 3,5-NDPS in rats. Male Sprague-Dawley or Fischer 344 rats were administered a single intraperitoneal injection of a N-(dichlorophenyl)succinimide (0.4 or 1.0 mmol/kg) or vehicle (2.5 ml/kg), and renal function was monitored at 24 and 48 hr. The most nephrotoxic NDPS isomer in both rat strains was 3,5-NDPS. In Sprague-Dawley rats 2,4-, 2,5- and 3,4-NDPS were weakly nephrotoxic. In Fischer 344 rats, 2,4-NDPS (1.0 mmol/kg) and 3,5-NDPS (0.4 mmol/kg) produced similar nephrotoxicity. Weak renal effects were produced by 3,4-NDPS in Fischer 344 rats. The order of increasing nephrotoxicity did not correlate well with the increasing partition coefficients or fungicidal activities of the compounds. These results indicate that 3,5-NDPS is the most nephrotoxic NDPS isomer in rats, and that partition coefficients alone are not good predictors of nephrotoxic potential in this series. In addition, these results do not support a correlation between the fungicidal and nephrotoxic mechanisms of action of these compounds.

Animals↗
PubMed1985

Structure-nephrotoxicity relationships for para-substituted N-phenylsuccinimides in Sprague-Dawley and Fischer 344 rats.

N-(3,5-Dichlorophenyl)succinimide (NDPS) has proven to be one of the most nephrotoxic compounds of a series of N-(halophenyl)succinimides. Previous studies in our laboratory have demonstrated that chlorine content and position on the phenyl ring are important determinants for NDPS-induced nephrotoxicity. The purpose of this study was to investigate the relationship between the electron donating or withdrawing nature of phenyl group substituents and the nephrotoxic potential of the corresponding fungicides. Rats were administered a para-substituted N-phenylsuccinimide (0.4 or 1.0 mmol/kg, i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 h and 48 h. In Sprague-Dawley rats, a clear nephrotoxicity was produced by NDPS. Weak nephrotoxicity was produced by N-(4-tert-butylphenyl)succinimide (NBPS). NDPS also was the most nephrotoxic compound in Fischer 344 rats, while weak nephrotoxicity was produced by NBPS. Lipophilic character (e.g. partition coefficient) did not correlate with acute nephrotoxicity in either rat strain. These results also indicate that there is a no correlation between the electronic nature of the phenyl substituents and resulting nephrotoxicity.

Animals↗
PubMed1985

In vivo and in vitro effects of azaconazole on renal function in the Fischer 344 rat.

Azaconazole is an experimental agricultural fungicide which has shown promise for use in controlling powdery mildew on crops and bean rust. This study examined the nephrotoxic potential of a single intraperitoneal azaconazole injection (0.4 or 0.6 mmol/kg) or daily azaconazole administration (0.1 or 0.3 mmol/kg/day) for 7 days in male Fischer 344 rats. The in vitro effects of azaconazole on the accumulation of organic ions by renal cortical slices also were examined. Acute azaconazole administration (0.4 or 0.6 mmol/kg, i.p.) produced a marked decrease in urine volume at 6 h. By 48 h urine volume was still decreased in the 0.6-mmol/kg group but not the 0.4-mmol/kg group. Proteinuria (++) and slight hematuria were seen in the 0.6-mmol/kg group on both treatment days. Accumulation of p-aminohippurate (PAH) by renal cortical slices was stimulated in both azaconazole-treated groups while tetraethylammonium (TEA) accumulation was not altered. No changes in blood urea nitrogen concentration, kidney weight or renal morphology were produced at 48 h postinjection by either azaconazole dose. Daily administration of azaconazole (0.1 or 0.3 mmol/kg/day) did not significantly alter any of the renal parameters studied. Incubation of renal cortical slices with increasing concentrations of azaconazole from 10(-5) M to 10(-3) M caused a continued reduction in TEA accumulation. PAH accumulation was decreased significantly following incubation with azaconazole 10(-5) or 10(-3) M. These results indicate that azaconazole is capable of producing acute, reversible renal effects at doses equal to or less than 0.6 mmol/kg and altering organic ion transport both in vivo and in vitro. The lack of marked renal effects following exposure to azaconazole is favorable for the development of this compound as an agricultural fungicide.

Animals↗
PubMed1985

Effect of succinimide ring modification on N-(3,5-dichlorophenyl)succinimide-induced nephrotoxicity in Sprague-Dawley and Fischer 344 rats.

N-(3,5-Dichlorophenyl)succinimide (NDPS) has proven to be an effective experimental agricultural fungicide. However, NDPS produces marked nephrotoxicity in Sprague-Dawley and Fischer 344 rats. The purpose of this study was to determine the importance of an intact, unsubstituted succinimide ring for acute NDPS-induced nephrotoxicity. Structural modifications included ring opening, reduction of one or both carbonyl groups, breaking the ethylene carbon-carbon bond and mono- or dialkyl substitution on the succinimide ring. Sprague-Dawley or Fischer 344 rats were administered NDPS or an NDPS analog (0.1, 0.2, 0.4, 0.8 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg, i.p.) and renal function was monitored at 24 h and 48 h. All structural modifications produced compounds with markedly reduced nephrotoxic potential in both Sprague-Dawley and Fischer 344 rats when compared to NDPS. However, N,N-diacetyl-3,5-dichloroaniline and N-(3,5-dichlorophenyl)pyrrolidine-2-one were more lethal than NDPS. The reduced renal effects of the NDPS analogs did not correlate with lipophilic character. These results indicate that an intact, unsubstituted succinimide ring is optimal for acute NDPS-induced nephrotoxicity.

Animals↗
PubMed1985

N-(3,5-Dichlorophenyl)succinimide nephrotoxicity in the Fischer-344 rat.

The nephrotoxic potential of N-(3,5-dichlorophenyl)succinimide (NDPS) was examined, in male Fischer-344 rats. Rats were administered NDPS (0.1, 0.2, 0.4 or 1.0 mmol/kg intraperitoneally (i.p.) or sesame oil (2.5 ml/kg, i.p.), and renal function was monitored at 24 and 48 h. NDPS (0.1 mmol/kg) stimulated organic ion uptake at 48 h. NDPS (0.2 mmol/kg) produced diuresis but did not alter blood urea nitrogen (BUN), kidney weight or organic ion uptake by renal cortical slices at 48 h. High-dose NDPS (0.4 and 1.0 mmol/kg) administration produced diuresis, decreased accumulation of p-aminohippurate (PAH) and tetraethylammonium (TEA), increased BUN and kidney weight and caused acute tubular necrosis. At 24 h, NDPS (0.2 mmol/kg) decreased uptake of PAH and TEA and tended to increase BUN. These results are similar to previous reports of NDPS-induced nephrotoxicity in Sprague-Dawley rats and suggest that either rat model would be suitable for future studies on the mechanism(s) of NDPS-induced nephropathy.

Animals↗
PubMed1985

Aminotetralone analogues of ketamine: synthesis and evaluation of hypnotic and locomotor properties in mice.

Ketamine and phencyclidine are structurally similar compounds that share many pharmacological actions, some of which are similar to the phenethylamines amphetamine and cathione. In order to integrate structural features of ketamine and cathinone, two groups of analogues, which are more conformationally restricted compared to the parent compounds, were synthesized for biological evaluation. These included 1-amino-1-methyl-2-tetralone and 2-amino-2-methyl-1-tetralone was well as several N-substituted derivatives of these molecules. Locomotor activity testing in mice revealed that 2-amino-2-methyl-1-tetralone caused an increase in locomotor activity while 1-amino-1-methyl-2-tetralone depressed spontaneous locomotor activity. None of the compounds produced hypnosis or profound ataxia.

Alkaloids↗