Histological changes in the liver and indices of drug metabolism in alcoholics

Sotaniemi, Eero A.; Ahlqvist, Johan; Pelkonen, R; Pirttiaho, H; Luoma, P. V.

doi:10.1007/bf00607680

Cited by 77 publications

(39 citation statements)

References 33 publications

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“…These findings suggest that a moderate fatty infiltration has only a minor influence on hepatic drug metabolism as a whole but its main consequence is a 'dilution' effect appearing in those parameters measured per unit weight or volume of the liver. These observations in diabetics are comparable with earlier results indicating fairly normal drug metabolism in alcoholics with fatty liver (Sotaniemi et al, 1977). Consistent with earlier studies (Homeida et al, 1979), the results also show the superiority of relative antipyrine clearance over absolute clearance in discriminating subjects with normal liver from those with altered liver parenchyma.…”

Section: Discussionsupporting

confidence: 92%

Drug metabolism in diabetic subjects with fatty livers.

Pirttiaho¹,

Pi²,

Ea³

et al. 1984

Brit J Clinical Pharma

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1 The effect of fatty degeneration of liver parenchyma on drug metabolism was investigated in 21 obese non-insulin-dependent diabetic subjects by measuring plasma antipyrine kinetics, hepatic cytochrome P-450, liver size and the extent of fatty infiltration. 2 The hepatic drug metabolising capacity, as measured by total antipyrine clearance and the estimated total amount of cytochrome P-450, was at the same level as in nondiabetic control subjects with normal livers. 3 Relative antipyrine clearance (per unit weight of liver) and cytochrome P-450 concentrations were significantly lower in the diabetics than in controls. 4 The extent of fatty infiltration correlated poorly with the indices of drug metabolism. 5 In non-insulin-dependent diabetics, slight to moderate hepatic fatty infiltration, without more serious structural distortion interfering with hepatic blood flow or hepatocellular function, seems to have only a minor influence on drug metabolism.

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Section: Discussionsupporting

confidence: 92%

Drug metabolism in diabetic subjects with fatty livers.

Pirttiaho¹,

Pi²,

Ea³

et al. 1984

Brit J Clinical Pharma

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“…The protocol, antipyrine assay in plasma samples and calculation ofclearance, half-time and volume of distribution were as previously described in detail (Sotaniemi et al, 1977;Pelkonen et al, 1985).…”

Section: Antipyrine Determinationmentioning

confidence: 99%

The effect of cigarette smoking on 7‐ethoxyresorufin O‐deethylase and other monooxygenase activities in human liver: analyses with monoclonal antibodies.

Pelkonen¹,

Pasanen²,

Kuha³

et al. 1986

Brit J Clinical Pharma

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1 Four cytochrome P-450 enzyme activities, 7-ethoxyresorufin O-deethylase (ERDE), coumarin 7-hydroxylase (CH), 7-ethoxycoumarin 0-deethylase (ECDE) and aryl hydrocarbon hydroxylase (AHH) were measured in human liver needle biopsy samples from smokers and non-smokers. Cigarette smoking was verified and quantitated by measuring plasma cotinine levels.3 Enzyme inhibitory monoclonal antibodies (MAb) to a 3-methylcholanthrene-induced (MAb 1-7-1) and phenobarbitone-induced (MAb 2-66-3) rat hepatic cytochrome P-450 were used to measure the contribution of MAb-defined, epitope-specific cytochromes P-450 to the total reaction measured for each of the above activities. 3 ERDE activity was significantly elevated in the livers of cigarette smokers, whereas AHH, CH or ECDE activities were not affected by cigarette smoking. No correlation was observed between plasma cotinine concentration and ERDE activity. 4 MAb 1-7-1 inhibited hepatic ERDE activity to a variable extent (from 0 to 65%), but had very little or no effect on AHH, CH or ECDE activities. The inhibitory effect of MAb 1-7-1 on ERDE activity was greater than 50% in the non-smokers. MAb 2-66-3 had no inhibitory effect on any of the enzyme activities studied. 5 In contrast to liver both ERDE and AHH on human placental microsomes from cigarette smokers were inhibited by MAb 1-7-1. The MAb 2-66-3 was without effect. 6 Cigarette smoking induces a form of P-450 in human liver, responsible for ERDE activity, that contains an epitope recognized by MAb 1-7-1. This form of cytochrome P-450 is insensitive to MAb 2-66-3 and is not contributing to AHH, CH or ECDE activities of human liver.

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“…The liver is the major site of metabolism of various hydrophobic compounds (1, 2), and drug metabolizing activity decreases in chronic liver disease, especially in liver cirrhosis (3,4). This decrease of the activity mainly depends on the damage of P-450 (4), which is the principal component of the mixed-function oxidase system in liver microsomes.…”

Section: Discussionmentioning

confidence: 99%

“…In patients with chronic liver disease, especially with liver cirrhosis, the elimination of several drugs is impaired with the advance in histological and functional impairment of the liver. For example, the elimination half-life of antipyrine is obviously prolonged in chronic active hepatitis and liver cirrhosis (3); the content of P-450 is reduced in proportion to the severity of hepatic parenchymal changes (4). Carbon tetrachloride (CC14) has been widely used to develop an appropriate animal model of liver cirrhosis (5).…”

Section: Many Hydrophobicmentioning

confidence: 99%

Drug Metabolizing Activity in Rats with Chronic Liver Injury Induced by Carbon Tetrachloride: Relationship with the Content of Hydroxyproline in the Liver

Okuno

Hazama

Murase

et al. 1986

Japanese Journal of Pharmacology

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Abstract-The drug metabolizing activity of rat liver during long-term adminis tration of carbon tetrachloride (CC14), and its relationship with the content of hydroxyproline (Hyp) in the liver were examined. The contents of cytochrome P-450 (P-450) and cytochrome b5 (b5) and the metabolization of aniline, aminopyrine, 7-ethoxycoumarin (7-EC) and benzo(a)pyrene (B(a)P) in the microsomal fraction were examined five days after the final administration of CC14. The contents of P-450 and b5 and the activity to metabolize the four substrates were gradually reduced as the Hyp content in the liver increased. However, aminopyrine N-demethylation and B(a)P hydroxylation, particularly the latter, was more reduced than aniline hydroxylation and 7-EC 0-deethylation in the early stage of hepatic fibrosis. Such differences may be due mainly to the different P-450 subtypes affected by CC14.

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Histological changes in the liver and indices of drug metabolism in alcoholics

Cited by 77 publications

References 33 publications

Drug metabolism in diabetic subjects with fatty livers.

Drug metabolism in diabetic subjects with fatty livers.

The effect of cigarette smoking on 7‐ethoxyresorufin O‐deethylase and other monooxygenase activities in human liver: analyses with monoclonal antibodies.

Drug Metabolizing Activity in Rats with Chronic Liver Injury Induced by Carbon Tetrachloride: Relationship with the Content of Hydroxyproline in the Liver

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