Partial hepatectomy reduces both metabolism and toxicity of benzene

Sammett, David; Lee, E. W.; Kocsis, James J.; Snyder, Robert

doi:10.1080/15287397909529789

Cited by 148 publications

(60 citation statements)

References 21 publications

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“…In agreement with the concept of Sammet et al (44) that hepatic metabolism plays a very important role in producing benzene-induced hemopoietic disorder, ethanol con sumption potentiated the toxicity of benzene (37,58). In contrast, phenobarbital produced a protective effect on toxicity (21,37).…”

Section: Phenobarbital As a Clue To The Underlying Mechanism Of The Dsupporting

confidence: 74%

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Sato¹,

Nakajima²

1987

Scand J Work Environ Health

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SATO A, NAKAJIMA T. Pharmacokinetics of organic solvent vapors in relation to their toxicit y. Scand J Work Environ Health 13 (1987) 81-93 . The volatility and Iipophilicity by which organi c solvents are distinct from other chemicals constitut e a characteristic pharmacokinetic feature . They enter a living body by inhalation, preferentially distribute in the adipose tissue, and are eliminated by both expirat ion and metabolic degradation. Th is review article is centered on experiment al studies conducted by the authors and their co-workers, and it deals with (i) pharmacokinetic principl es, (ii) partition coefficients in relation to toxicity, (iii) significance of metabolism in the developmen t of organic solvent toxicity, and (iv) environmental factors that alt er the metabolism and toxicity of solvents.

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Section: Phenobarbital As a Clue To The Underlying Mechanism Of The Dsupporting

confidence: 74%

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Sato¹,

Nakajima²

1987

Scand J Work Environ Health

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“…Thus, inhibition of benzene metabolism by toluene, a competitive inhibitor, results in a decrease in benzene metabolism and a reduction in benzene toxicity (4). Decreasing the hepatic metabolism of benzene by partial hepatectomy also reduced benzene toxicity, suggesting that hepatic metabolism plays an important role in toxicity (5).…”

Section: Benzene Metabolism and Toxicitymentioning

confidence: 99%

An Overview of Benzene Metabolism

Snyder¹,

Hedli²

1996

Environ Health Perspect

105

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Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity.

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“…Previous research has shown that benzene itself is probably not the actual toxicant, but is converted by hepatic metabolism to a metabolite(s) that travels to the bone marrow and exerts its toxic effects (1,2). There is, however, also the potential for benzene to be directly activated within the bone marrow itself (3).…”

Section: Introductionmentioning

confidence: 96%