A Dynamic Liver Culture System: A Tool for Studying Chemical Biotransformation and Toxicity

Sipes, I. G.; Fisher, Ron; Smith, Peter F.; Stine, E.R.; Gandolfi, A. Jay; Brendel, Klaus

doi:10.1007/978-3-642-72558-6_3

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…They are easily prepared from different animal species, including man, using the same method and they closely resemble the organ from which 90 they are derived. Liver slices can retain their normal liver hepatocyte population and their physiological and biochemical functions for many hours [5,6]. Successful experimentation depends on the maintainance of slice viability over the designated experimental period.…”

Section: Introductionmentioning

confidence: 99%

Enzymatic Oxidation of Vanillin, Isovanillin and Protocatechuic Aldehyde with Freshly Prepared Guinea Pig Liver Slices

Panoutsopoulos

Beedham

2005

Cell Physiol Biochem

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Background/Aims: The oxidation of xenobiotic-derived aromatic aldehydes with freshly prepared liver slices has not been previously reported. The present investigation compares the relative contribution of aldehyde oxidase, xanthine oxidase and aldehyde dehydrogenase activities in the oxidation of vanillin, isovanillin and protocatechuic aldehyde with freshly prepared liver slices. Methods: Vanillin, isovanillin or protocatechuic aldehyde was incubated with liver slices in the presence/absence of specific inhibitors of each enzyme, followed by HPLC. Results: Vanillin was rapidly converted to vanillic acid. Vanillic acid formation was completely inhibited by isovanillin (aldehyde oxidase inhibitor), whereas disulfiram (aldehyde dehydrogenase inhibitor) inhibited acid formation by 16% and allopurinol (xanthine oxidase inhibitor) had no effect. Isovanillin was rapidly converted to isovanillic acid. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. Protocatechuic aldehyde was converted to protocatechuic acid at a lower rate than that of vanillin or isovanillin. Allopurinol only slightly inhibited protocatechuic aldehyde oxidation, isovanillin had little effect, whereas disulfiram inhibited protocatechuic acid formation by 50%. Conclusions: In freshly prepared liver slices, vanillin is rapidly oxidized by aldehyde oxidase with little contribution from xanthine oxidase or aldehyde dehydrogenase. Isovanillin is not a substrate for aldehyde oxidase and therefore it is metabolized to isovanillic acid predominantly by aldehyde dehydrogenase. All three enzymes contribute to the oxidation of protocatechuic aldehyde to its acid.

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Section: Introductionmentioning

confidence: 99%

Enzymatic Oxidation of Vanillin, Isovanillin and Protocatechuic Aldehyde with Freshly Prepared Guinea Pig Liver Slices

Panoutsopoulos

Beedham

2005

Cell Physiol Biochem

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“…They are easily prepared from different animal species and they resemble the organ from which they are derived. They can retain their normal liver hepatocyte population and their physiological and biochemical functions for many hours [26,27].…”

Section: Introductionmentioning

confidence: 99%

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

Panoutsopoulos

Beedham

2005

Pharmacology

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Aromatic aldehydes are good substrates of aldehyde dehydrogenase activity but are relatively poor substrates of aldehyde oxidase and xanthine oxidase. However, the oxidation of xenobiotic-derived aromatic aldehydes by the latter enzymes has not been studied to any great extent. The present investigation compares the relative contribution of aldehyde dehydrogenase, aldehyde oxidase and xanthine oxidase activities in the oxidation of isovanillin in separate preparations and also in freshly prepared and cryopreserved liver slices. The oxidation of isovanillin was also examined in the presence of specific inhibitors of each oxidizing enzyme. Minimal transformation of isovanillin to isovanillic acid was observed in partially purified aldehyde oxidase, which is thought to be due to residual xanthine oxidase activity. Isovanillin was rapidly metabolized to isovanillic acid by high amounts of purified xanthine oxidase, but only low amounts are present in guinea pig liver fraction. Thus the contribution of xanthine oxidase to isovanillin oxidation in guinea pig is very low. In contrast, isovanillin was rapidly catalyzed to isovanillic acid by guinea pig liver aldehyde dehydrogenase activity. The inhibitor studies revealed that isovanillin was predominantly metabolized by aldehyde dehydrogenase activity. The oxidation of xenobiotic-derived aromatic aldehydes with freshly prepared or cryopreserved liver slices has not been previously reported. In freshly prepared liver slices, isovanillin was rapidly converted to isovanillic acid, whereas the conversion was very slow in cryopreserved liver slices due to low aldehyde dehydrogenase activity. The formation of isovanillic acid was not altered by allopurinol, but considerably inhibited by disulfiram. It is therefore concluded that isovanillin is predominantly metabolized by aldehyde dehydrogenase activity, with minimal contribution from either aldehyde oxidase or xanthine oxidase.

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“…The measured parameters were the reduction in the intracellular level of K + , the inhibition of protein biosynthesis and the release of lactate dehydrogenase. 1,4-Dichlorobenzene had only weak hepatotoxic effects in F344 rats and none in Sprague-Dawley rats [54].…”

Section: Other Effectsmentioning

confidence: 86%

“…A single intraperitoneal injection of 1,4-dichlorobenzene had no effect on the serum ALT activity in male Fischer 344 rats (dose range 132-662 mg/kg body weight) or in male Sprague-Dawley rats (doses 265 and 795 mg/kg body weight) [53,54].…”

Section: Acute Toxicitymentioning

confidence: 99%

1,4‐Dichlorobenzene [MAK Value Documentation, 1992]

2012

The MAK‐Collection for Occupational Health and Safety

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Published in the series Occupational Toxicants , Vol. 4 (1992) The article contains sections titled: Toxic Effects and Modes of Action Pharmacokinetics Effects in Man Effects on Animals Acute toxicity Subacute and subchronic toxicity Reproductive and Developmental Toxicity Genotoxicity and DNA‐Binding Carcinogenicity α 2µ ‐Globulin nephropathy in male rats treated with 1,4‐dichlorobenzene Other Effects Manifesto (MAK value, classification)

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A Dynamic Liver Culture System: A Tool for Studying Chemical Biotransformation and Toxicity

Cited by 23 publications

References 15 publications

Enzymatic Oxidation of Vanillin, Isovanillin and Protocatechuic Aldehyde with Freshly Prepared Guinea Pig Liver Slices

Enzymatic Oxidation of Vanillin, Isovanillin and Protocatechuic Aldehyde with Freshly Prepared Guinea Pig Liver Slices

Metabolism of Isovanillin by Aldehyde Oxidase, Xanthine Oxidase, Aldehyde Dehydrogenase and Liver Slices

1,4‐Dichlorobenzene [MAK Value Documentation, 1992]

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