Studies on the toxicology of hexachlorobenzene

Koss, G.; Seubert, S.; Seubert, Andreas; Seidel, Jutta; Koransky, W.; Ippen, H

doi:10.1007/bf00317978

Cited by 35 publications

(6 citation statements)

References 23 publications

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“…Worth pointing out, the high discrepancy observed between the HCB administered and the serum concentrations responds to the fact that only 2-5% HCB is absorbed when administered as an aqueous suspension (Koss and Koransky, 1975).…”

Section: Discussionmentioning

confidence: 99%

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

et al. 2018

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Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-β1 (TGF-β1) mRNA and angiotensin II type1 receptor (AT), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-β1, AT1, ERα, eNOS and DII.

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Section: Discussionmentioning

confidence: 99%

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

et al. 2018

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“…Prolonged inhibition of the enzyme does not appear to be dirfctly correlated with levels of HCB in the liver or with inductions of total cytochrome P-450 and microsomal ethoxyphenoxazone de-ethylase activity. If these parameters are involved in the inhibition they must still be sufficient after 14 weeks to maintain the depression of uroporphyrinogen decarboxylase activity (Koss et al, 1983;Khanna & Smith, 1985;. The accumulation of liver porphyrins is probably potentiated by induction of aminolaevulinate synthase (EC 2.3.1.37) (Wainstok de Calmanovici et al, 1984) partly explaining the disparities between decarboxylase inhibition and porphyrin levels that were sometimes observed.…”

Section: Incubations Of Hcb-induced Microsomes With Control Cytosolmentioning

confidence: 99%

Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism

Smith¹,

Francis²,

Kay³

et al. 1986

Biochemical Journal

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Porphyria was induced in C57BL/10 mice with iron overload by a single oral dose (100 mg/kg) of hexachlorobenzene (HCB). Within 2 weeks hepatic uroporphyrinogen decarboxylase (EC 4.1.1.37) was inhibited, reaching a maximum (greater than 95%) at 6-8 weeks. There was no recovery by 14 weeks, despite a fall in liver HCB concentrations to only 6% of the day-3 value. The major rise in hepatic porphyrin levels occurred after 4 weeks and secondary inhibition of uroporphyrinogen synthase (EC 4.2.1.75) was inferred from the progressively greater proportion of uroporphyrin I present relative to the III isomer. Plasma alanine aminotransferase (EC 2.6.1.2) activity was also elevated. Although, in further studies, total microsomal cytochrome P-450 content and ethoxyphenoxazone de-ethylase activity reached a peak a few days after dosing and had declined significantly at the time of maximum inhibition of the decarboxylase, additional treatment of HCB-dosed mice with a cytochrome P1-450 inducer, beta-naphthoflavone, enhanced the inhibition, whereas piperonyl butoxide, an inhibitor of cytochrome P-450, partially protected. Uroporphyrinogen decarboxylase was not radiolabelled in vivo by [14C]HCB. There was no major difference in the ability to hydroxylate HCB between hepatic microsomes from induced C57BL/10 mice and those from the insensitive DBA/2 strain. By contrast, lipid peroxidation, in the presence of NADPH, was 8-fold greater in control C57BL/10 microsomes than in DBA/2 microsomes and was stimulated by iron treatment (although not by HCB). The results suggest that the inhibition of hepatic uroporphyrinogen decarboxylase is unlikely to be due to a direct effect of a metabolite of HCB but to another process requiring a specific cytochrome P-450 isoenzyme and an unknown iron species.

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“…Another major metabolic pathway observed in rodents is the conjugation of HCB with glutathione (12). The glutathione conjugate is further metabolized by cleavage of the glycine and glutamate residues to become pentachlorophenyl-Nacetyl-L-cysteine.…”

mentioning

confidence: 99%

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

To‐Figueras

Sala

Rial-Otero

et al. 1997

Environ Health Perspect

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Serum and urine from 100 subjects of a general population highly exposed to airborne hexachlorobenzene (HCB) were analyzed to obtain new insights into the metabolism of this ubiquitous compound. HCB was detected in all serum samples with concentrations ranging between 1.1 and 953 ng/ml. The major known metabolites of HCB were investigated in urine collected over 24 hr. Pentachlorophenol (PCP) was detected in all urines with values ranging between 0.58 and 13.9 micrograms excreted in 24 hr [mean +/- standard deviation (SD), 2.52 +/- 2.05; geometric mean, 2.05]. A sulfur derivative that, after hydrolysis, yielded pentachlorobenzenethiol (PCBT) could also be identified and quantified in all the urines with values ranging between 0.18 and 84.0 micrograms of PCBT excreted in 24 hr (mean +/- SD, 3.47 +/- 10.8; geometric mean, 1.39). The sulfur derivative assessed as PCBT appeared to be the main metabolite, with urinary concentrations surpassing those of PCP in the subjects with higher HCB accumulation (HCB in serum > 32 ng/ml). PCBT concentration in urine collected over 24 hr showed a very strong association with HCB concentration in serum; the association was stronger in males than in females. An increase of 1 ng/ml of HCB in serum led to an increase of 2.12 micrograms of PCBT excreted in urine collected over 24 hr in males (95% CI, 1.82-2.44) and to an increase of 0.67 microgram of PCBT in females (CI, 0.33-1.09). A weaker association was found between PCP in urine and HCB in serum, which was only statistically significant in males (an increase of 1 ng/ml of HCB in serum led to an increase of 0.63 microgram of PCP excreted in urine collected over 24 hr; (CI, 0.34-0.95). These results show that the formation of the cysteine conjugate is a quantitatively more important metabolic pathway in humans than the formation of PCP. Moreover, the association found suggests that PCBT is a good urinary marker of HCB internal dose and glutathione-mediated metabolism.ImagesFigure 1.Figure 2. AFigure 2. BFigure 3. AFigure 3. B

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Studies on the toxicology of hexachlorobenzene

Cited by 35 publications

References 23 publications

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

Mechanistic studies of the inhibition of hepatic uroporphyrinogen decarboxylase in C57BL/10 mice by iron-hexachlorobenzene synergism

Metabolism of hexachlorobenzene in humans: association between serum levels and urinary metabolites in a highly exposed population.

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