Biochemical effects of pure isomers of hexachlorobiphenyl: Fatty livers and cell structure

Kohli, Krishan K.; Gupta, B. N.; Albro, Phillip W.; Mukhtar, Hasan; McKinney, James D.

doi:10.1016/0009-2797(79)90042-5

Cited by 38 publications

(7 citation statements)

References 19 publications

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“…We have previously reported that HCBP-1 {with two para substituents) was a mixed-type inducer and it is apparent from the results that pretreatment of rats with either HCBP-2 (with one para substituent) or HCBP-3 {with no para substituents) resulted in a PB-type enhancement of hepatic microsomal B[a]P hydroxylase and DMAP N-demethylase activities and cytochrome P-450 content, pA fourth isomer devoid of para substituents, HCBP-4, exhibited only marginal PB-type activity. These data and previous results reported for 2,2',3,3',5,5'-hexachlorobiphenyl [22,23] demonstrate that para chloro substitution of biphenyl is not a structural requirement for PB-type induction.…”

Section: Discussionsupporting

confidence: 86%

“…More recent studies with highly purified PCB isomers and congeners have shown that, in contrast to rule (2), certain compounds chlorinated in the meta and para positions of both rings and at only one ortho position are mixed (PB+MC)-type inducers [20,21]. Similarly, in contrast to rule {1), 2,2',3,3',5,5'-hexachlorobiphenyl, an isomer with no para chloro substituents, was shown to be a PB-type inducer [22,23].…”

Section: Introductionmentioning

confidence: 95%

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Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules

Parkinson

Robertson

Safe

et al. 1980

Chemico-Biological Interactions

124

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A number of highly purified polychlorinated biphenyl (PCB) isomers and congeners were synthesized and administered to male Wistar rats at dosage levels of 30 and 150 mumol . kg-1. The effects of this in vivo treatment on the drug-metabolizing enzymes were determined by measuring the microsomal benzo[a]pyrene (B[a]P) hydroxylase, dimethylaminoantipyrine (DMAP) N-demethylase and NADPH-cytochrome c reductase enzyme activities, the cytochrome b5 content and the relative peak intensities and spectral shifts of the reduced microsomal cytochrome P-450 CO and ethylisocyanide (EIC) binding difference spectra. The results were compared to the effects of administering phenobarbitone (PB), 3-methylcholanthrene (MC) and PB plus MC (coadministered) to the test animals. The synthetic PCB congeners used in this study included 3,4,4',5-tetrachlorobiphenyl (TCBP-1), 2,3',4,4'-tetrachlorobiphenyl (TCBP-2), 2,3',4,4',5'-pentachlorobiphenyl (PCBP-1), 2,3,4,-4',5-pentachlorobiphenyl (PCBP-2), 2,3,3',4,4',5-hexachlorobiphenyl (HCBP-1) 2,3',4',5,6-hexachlorobiphenyl (HCBP-2), 2,3,3',5,5',6-hexachlorobiphenyl (HCBP-3), 2,2',3,5,5',6-hexachlorobiphenyl (HCBP-4) and 2,3,3',4,5,5'-hexachlorobiphenyl (HCBP-5) and were used to reappraise the structure-activity rules for PCBs as hepatic microsomal enzyme inducers. The results suggested that (a) PCBs which induce MC or mixed-type activity must be substituted at both para positions, at least two meta positions but not necessarily on the same phenyl ring and can also contain one ortho chloro substituent; (b) due to the considerable structural diversity of the PB-type inducers the rules for induction of this activity by PCB congeners are not readily defined.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 95%

Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules

Parkinson

Robertson

Safe

et al. 1980

Chemico-Biological Interactions

124

View full text Add to dashboard Cite

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“…Hennig et al (2005) reported that the same dose of PCB-77 increased body mass, fatty liver, abdominal fat, and adipocyte hypertrophy in CVD mice. Fatty liver, attributed to increased hepatic triglycerides and cholesterol, was also observed in mice treated with 50 mg DL PCB-169/kg body weight (Kohli et al 1979). …”

Section: At As a Target Of Pollutantsmentioning

confidence: 99%

Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants

Merrill

Emond

Kim

et al. 2013

Environ Health Perspect

282

220

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Background: Adipose tissue (AT) is involved in several physiological functions, including metabolic regulation, energy storage, and endocrine functions.Objectives: In this review we examined the evidence that an additional function of AT is to modulate persistent organic pollutant (POP) toxicity through several mechanisms.Methods: We reviewed the literature on the interaction of AT with POPs to provide a comprehensive model for this additional function of AT.Discussion: As a storage compartment for lipophilic POPs, AT plays a critical role in the toxicokinetics of a variety of drugs and pollutants, in particular, POPs. By sequestering POPs, AT can protect other organs and tissues from POPs overload. However, this protective function could prove to be a threat in the long run. The accumulation of lipophilic POPs will increase total body burden. These accumulated POPs are slowly released into the bloodstream, and more so during weight loss. Thus, AT constitutes a continual source of internal exposure to POPs. In addition to its buffering function, AT is also a target of POPs and may mediate part of their metabolic effects. This is particularly relevant because many POPs induce obesogenic effects that may lead to quantitative and qualitative alterations of AT. Some POPs also induce a proinflammatory state in AT, which may lead to detrimental metabolic effects.Conclusion: AT appears to play diverse functions both as a modulator and as a target of POPs toxicity.

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“…In rats single high oral dose of certain PCBs [ 20 ] and OCPs [ 21 ] increases deposition of triglycerides to liver. These effects may also depend on the diet.…”

Section: Introductionmentioning

confidence: 99%

Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly obese patients: a cohort study

et al. 2015

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BackgroundIn animal experiments persistent organic pollutants (POPs) cause hepatosteatosis. In epidemiological studies POPs have positive associations with serum markers of nonalcoholic fatty liver disease (NAFLD) and together with obesity synergistic association with insulin resistance. Because insulin resistance and obesity are critical in NAFLD pathogenesis, we investigated the association of serum pollutant levels with liver histology and alanine aminotransferase (ALT) in morbidly obese.MethodsLiver biopsies were from 161 participants of the Kuopio Obesity Surgery Study (KOBS) who underwent bariatric surgery 2005–2011. Liver histology was categorized as normal, steatosis and non-alcoholic steatohepatitis (NASH). Liver phenotype at baseline and ALT at baseline and 12 months post-surgery were correlated to serum POP concentrations at respective time points. As lipophilic POPs concentrate to smaller fat volume during weight loss, serum levels before and 12 months after bariatric surgery were compared.ResultsBaseline serum concentration of PCB-118, β-HCH and several PFAAs had an inverse association with lobular inflammation possibly due to changes in bile acid metabolism. ALT had negative associations with many POPs at baseline that turned positive at 12 months after major clinical improvements. There was an interaction between some POPs and sex at 12 months, and in stratified data positive associations were observed mainly in females but not in males.ConclusionsWe found a negative association between serum concentrations of PCB-118, β-HCH and several PFAAs with lobular inflammation at baseline. Positive POPs-ATL associations at 12 months among women suggest that increased POP concentrations may decrease the degree of liver recovery.Electronic supplementary materialThe online version of this article (doi:10.1186/s12940-015-0066-z) contains supplementary material, which is available to authorized users.

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Biochemical effects of pure isomers of hexachlorobiphenyl: Fatty livers and cell structure

Cited by 38 publications

References 19 publications

Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules

Polychlorinated biphenyls as inducers of hepatic microsomal enzymes: Structure-activity rules

Toxicological Function of Adipose Tissue: Focus on Persistent Organic Pollutants

Persistent organic pollutants and non-alcoholic fatty liver disease in morbidly obese patients: a cohort study

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