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Biomedical subjects

H H Lo

Publications and source records attributed to H H Lo.

At least 37 records · Page 2Linked to original sources
PubMed1993

Dietary fatty acid modulation of events associated with mouse skin tumor promotion.

Increasing levels of dietary corn oil have been correlated with inhibition of 12-O-tetradecanoylphorbol-13-acetate-(TPA) promoted skin tumorigenesis in mice (Leyton et al. Cancer Res. 51, 907-915, 1991). This study was undertaken to assess the effects of dietary corn oil on several events associated with tumor promotion. Three semipurified diets containing 15% (wt/wt) total fat with increasing levels of linoleate (0.8%, 4.5%, and 8.4%) supplied by corn oil were fed to mice for at least four weeks. Although incorporation of linoleate into epidermal phosphatidylcholine increased with increasing amounts of dietary corn oil, the elongated desaturated product of linoleate, arachidonate, was similar or decreased slightly in mice fed the three diets. Minimal activity of delta 6-desaturase, the rate-limiting enzyme in the conversion of linoleate to arachidonic acid, was found in the epidermis compared with the liver, suggesting that linoleate is not converted to arachidonic acid in the skin. Subcellular distribution of protein kinase C was altered in mice fed 0.8% linoleate, where 69% of protein kinase C activity was in the cytosol compared with 78% and 74% for groups fed 4.5% and 8.4% linoleate, respectively. Activation of partially purified protein kinase C isolated from mouse epidermis by linoleate was significantly lower (p < 0.01) than that isolated by arachidonic acid. TPA-induced vascular permeability was significantly greater (p < 0.05), whereas hyperplasia 48 hours after TPA treatment was significantly lower, in mice fed the 8.4% linoleate diet. However, TPA induction of ornithine decarboxylase activity did not appear to be significantly modified by dietary linoleate. These data suggest that cellular processes associated with carcinogenesis are affected by the level of dietary linoleate.

Animals↗
PubMed1991

Inhibition of gamma-glutamyl transpeptidase potentiates the nephrotoxicity of glutathione-conjugated chlorohydroquinones.

Administration of either 2,5-dichloro-3-(glutathion-S-yl)-1, 4-benzoquinone (DC-[GSyl]BQ) or 2,5,6-trichloro-3-(glutathion-S-yl)-1,4-benzoquinone (TC-[GSyl]BQ) to male Sprague-Dawley rats caused dose-dependent (50-200 mumol/kg; iv) renal proximal tubular necrosis, as evidenced by elevations in blood urea nitrogen (BUN), and in the urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and glucose. Renal proximal tubular necrosis was also confirmed by histological examination of kidney slices prepared from DC-(GSyl)BQ- and TC-(GSyl)BQ-treated animals. Administration of the corresponding hydroquinone conjugates (DC-[GSyl]HQ and TC-[GSyl]HQ), prepared by reducing the quinones with a threefold molar excess of ascorbic acid, resulted in a substantial increase in nephrotoxicity. Moreover, in contrast to other glutathione (GSH)-conjugated hydroquinones, the nephrotoxicity of both DC-(GSyl)HQ and TC-(GSyl)HQ was potentiated when rats were pretreated with AT-125, an irreversible inhibitor of gamma-GT. Neither the quinone-GSH nor the hydroquinone-GSH conjugates caused any effect on liver histology or serum glutamate-pyruvate transaminase levels. The results suggest that coadministration of ascorbic acid with DC-(GSyl)BQ or TC-(GSyl)BQ decreases their interactions with extrarenal nucleophiles, including plasma proteins, and thus increases the concentration of the conjugates delivered to the kidney, and hence toxicity. Furthermore the ability of AT-125 to potentiate the nephrotoxicity of DC-(GSyl)HQ and TC-(GSyl)HQ suggests that metabolism of these conjugates by gamma-GT constitutes a detoxication reaction.

Animals↗
PubMed1991

Trichloroaniline effects on renal function in vivo and in vitro.

Previous studies have demonstrated that mono- and dichloroanilines are capable of inducing acute renal failure in vivo and altering organic ion accumulation by renal cortical slices in vitro. The purpose of this study was to determine the nephrotoxic potential of 4 trichloroaniline (TCA) isomers in vivo and to examine their effects on organic ion accumulation in vitro. In the in vivo experiments, male Fischer-344 rats (4 rats/group) were administered a TCA (0.8 or 1.5 mmol/kg) intraperitoneally (i.p.) or vehicle (sesame oil, 2.5 ml/kg). Renal function was monitored at 24 and 48 h. None of the TCA isomers induced marked renal effects at either time point. In vitro, all TCA isomers were effective in decreasing tetraethylammonium and p-aminohippurate accumulation by renal cortical slices at bath concentrations of 10(-3) M with 2,3,4- and 3,4,5-TCA inducing the greatest reductions. These results indicate that TCA can have a direct effect on renal function in vitro, but that the isomers tested are less potent nephrotoxicants than the nephrotoxic mono- and dichloroanilines.

Aniline Compounds↗
PubMed1990

Acute nephrotoxicity induced by isomeric dichloroanilines in Fischer 344 rats.

Chlorinated anilines are widely used as chemical intermediates in the manufacture of numerous dyes, pesticides, drugs and industrial compounds. The purpose of this study was to examine the nephrotoxic potential of the six dichloroaniline (DCA) isomers in vivo and in vitro. In the in vivo studies, male Fischer 344 rats (4-8 rats/group) were administered a single, intraperitoneal injection of a DCA isomer (0.4, 0.8 or 1.0 mmol/kg) as the hydrochloride salt or given vehicle (0.9% saline, 2.5 ml/kg), and renal function monitored at 24 and 48 h. Renal effects induced by DCA were characterized by decreased urine volume, increased proteinuria, hematuria, modest elevations in blood urea nitrogen (BUN) concentrations, decreased accumulation of p-aminohippurate (PAH) by renal cortical slices, and no change or a slight decrease in kidney weight. Renal morphological changes were observed as proximal tubular necrosis with lesser effects on distal tubular cells and collecting ducts. Based on the overall effects on renal function and morphology, the decreasing order of nephrotoxic potential was found to be 3,5-DCA greater than 2,5-DCA greater than 2,4-, 2,6- and 3,4-DCA greater than 2,3-DCA. The ability for the DCA to induce nephrotoxicity correlated well with the lipophilic properties of the DCA isomers and Hammett constants (sigma) for the various chloro substitutions. In the in vitro studies, renal cortical slices from naive male Fischer 344 rats were co-incubated with a DCA isomer (0-10(-3) M) and PAH or tetraethylammonium (TEA). All DCA isomers decreased PAH and TEA accumulation at 10(-3) M DCA concentration in the media with 3,5-DCA inducing the largest decrease at this concentration. These results indicate that DCA are capable of altering renal function in vivo and in vitro and that 3,5-DCA possesses the greatest nephrotoxic potential in vivo and in vitro.

Aniline Compounds↗
PubMed1987

Structure-nephrotoxicity relationships for meta-substituted N-phenylsuccinimides.

The N-phenylsuccinimides are being evaluated as experimental agricultural fungicides. The purpose of this study was to examine the relationship between the electron withdrawing or electron donating properties of phenyl ring substituents on meta-substituted N-phenylsuccinimide (NPS) derivatives and the nephrotoxic potential of the corresponding fungicides. Male Fischer 344 rats were administered a single intraperitoneal injection of a succinimide (0.4 or 1.0 mmol/kg) or vehicle (sesame oil, 2.5 ml/kg), and renal function monitored at 24 and 48 hr. Non-halogen-substituted NPS derivatives produced little evidence of nephrotoxicity at the doses used in this study. Among the meta-halogen derivatives of NPS, N-(3-chlorophenyl)succinimide (NCPS) was the most nephrotoxic. NCPS-induced nephrotoxicity was characterized by diuresis, proteinuria, hematuria, elevated blood urea nitrogen (BUN) concentration, decreased organic ion accumulation and proximal tubular necrosis. However, all renal effects produced by NCPS were mild to moderate. These results suggest that the electron withdrawing or donating property of a functional group is not a good predictor of the nephrotoxic potential for the corresponding fungicide. In addition, lipophilicity did not correlate with nephrotoxic potential for the meta-substituted NPS derivatives evaluated in this study.

Animals↗
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↗
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↗
PubMed1979

The significance of augmented radiocolloid uptake by the spleen in patients with malignant melanoma.

Increase in splenic uptake of Tc-99m sulfur colloid was noted in 47 of 147 (32%) patients with cutaneous malignant melanoma early in the coure of disease. Patients with disseminated disease and/or clinical or laboratory evidence of hapatic dysfunction were excluded from study. Recurrence rate of 2 yr was higher for those patients with splenic scans demonstrating augmented uptake compared with patients having normal scans, 36% against 16% (p less than 0.02). These differences resulted from a much more favorable prognosis in women with normal scans contrasted with women with increased uptake, 6% against 26% (p less than 0.05). Women with increased splenic uptake, and all men regardless of scan status, seemed to have a higher rate of recurrence than women with normal spleen scans. Scan status may be an adjunctive prognostic marker in women.

Colloids↗
PubMed1977

Epithelioid sarcoma:radiologic and pathologic manifestations.

The radiologic and pathologic manifestations of epithelioid sarcoma are presented based on an analysis of five cases, and the literature is reviewed. This rare entity tends to orginate in the extremities and metastasizes primarily via the lymphatics. Although the lesion grows slowly, it recurs with high frequency. Males are affected three times as often as females. The differential diagnosis includes both malignant and benign entities. The natural history and methods of treatment are reported.

Adolescent↗