Enhanced Hepatic Microsomal Activity by Pretreatment of Rats with Acetone or Isopropanol

Sipes, I. G.; Stripp, Bitten; Krishna, Gopal; Maling, Harriet M.; Gillette, James R.

doi:10.3181/00379727-142-36996

Cited by 50 publications

(6 citation statements)

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“…The administration of propan-2-ol led to an increase in both aniline hydroxylation and aminopyrine demethylation associated with small increases in the yield of microsomal protein, in NADPHcytochrome c reductase and in NADPH-cytochrome P-450 reductase, although the concentrations of cytochrome P450 were unchanged. Sipes et al (1973) have reported that propan-2-ol administration increases dimethylnitrosamine demethylation, has no effect on microsomal cytochrome P450 and Vol. 148 their results also show a small increase in NADPHcytochrome c reductase.…”

Section: Discussionmentioning

confidence: 99%

“…Propan-2-ol is metabolized in the rat to acetone, a dose of30 mol ofpropan-2-ol/ kg being almost cleared from the blood in 18h (Traiger &1Plaa, 1972). Acetonemay account forsome of the effects of propan-2-ol; it has been found to induce microsomal aniline hydroxylation and NADPH-cytochrome c reductase but has no effect on cytochrome P450 and aminopyrine demethylation (Sipes et al, 1973;Clark & Powis, 1974).…”

Section: Discussionmentioning

confidence: 99%

“…It has been suggested that the ability of certain alcohols, administered as a single dose, to Vol. 148 potentiate the hepatotoxicity of carbon tetrachloride given to animals several hours later may be related to an increase in the hepatic microsomal metabolism of carbon tetrachloride (Sipes et al, 1973). The metabolism of other foreign compounds may also be increased.…”

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confidence: 99%

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Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat

Powis

1975

Biochemical Journal

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Methanol and ethanol administered to rats as a single oral dose increased aniline hydroxylation by the hepatic microsomal fraction by a maximum of 169 and 66% respectively, whereas aminopyrine demethylation was inhibited by 51 and 61%. The concentration of microsomal cytochrome P-450, and the activities of NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were unchanged. Propan-2-ol, administered as a single oral dose, increased microsomal aniline hydroxylation by 165% and increased aminopyrine demethylation by 83%. The concentration of cytochrome P-450 was unchanged whereas NADPH-cytochrome c reductase and NADPH-cytochrome P-450 reductase were both increased by 38%. Methanol, ethanol and propan-2-ol administration resulted in a decreased type I spectral change but had no effect on the reverse type I spectral change. Methanol administration decreased the type II spectral change whereas ethanol and propan-2-ol had no effect. Cycloheximide blocked the increases in aniline hydroxylation and aminopyrine demethylation but could not completely prevent the decreases in aminopyrine demethylation. The increases in aniline hydroxylation were due to an increase in V, but Km was unchanged. The ability of acetone to enhance and compound SKF 525A to inhibit microsomal aniline hydroxylation was decreased by the administration of all three alcohols. The decrease in the metabolism of aminopyrine may result from a decrease in the binding to the type I site with a consequent failure of aminopyrine to stimulate the reduction of cytochrome P-450. Methanol administration may lead to an increase in aniline hydroxylation because of a failure of aniline to inhibit cytochrome P-450 reduction.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat

Powis

1975

Biochemical Journal

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“…Although 3-methylcholanthrene pretreatment shifted the spectral peak to 448, cytochrome P-448 was determined in the same way. Ethylmorphine N-demethylase activity was measured as described by Sipes et al (15). Formaldehyde was measured by the method of Nash (16).…”

mentioning

confidence: 99%

Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases.

Byus¹,

Costa²,

Sipes³

et al. 1976

Proc. Natl. Acad. Sci. U.S.A.

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The parenteral administration of a single dose of 3-methylcholanthrene to rats caused an increase in the liver of the concentration of 3':5'-cAMP and of the activity of cAMP-dependent protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37). These events were followed by an increased activity of ornithine decarboxylase (L-ornithine carboxy-lyase, EC 4.1.1.17), the enzyme that controls the biosynthesis of polyamines. Finally, the activity of benzo[ahpyrene hydroxylase, as well as the amount of cytochrome P448, was increased. Similarly, after the administration of phenobarbital, there was first an increase in the cAMP concentration and in the activity of cAMP-dependent protein kinase, then the induction of ornithine decarboxylase, and finally, an enhanced activity of ethylmorphine N-demethylase and an increased content of cytochrome P-450. These data suggest that the drug-induced processes in liver that increase the activities of the oxidative, and presumably other, drugmetabolizing enzymes include the following sequence of

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“…Among a series of alcohols, isopropyl alcohol was the most effective in potentiating the elevated levels of hepatic enzyme activities [Traiger and Plaa, 19701. Although the mechanism by which isopropyl alcohol potentiates the hepatotoxicity of carbon tetrachloride is still unknown, metabolic interaction has been considered to be the major effect [Sipes et al, 1973;Glende and Lee, 19851. This study suggests that acute liver damage and renal failure may occur in workers following exposure to carbon tetrachloride at levels of 300-500 ppm when there is concomitant exposure to isopropyl alcohol. Therefore, the air concentration of CC4 alone that is needed to produce acute hepatic damage and renal failure may be above 300-500 ppm.…”

Section: Discussionmentioning

confidence: 99%

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan

Deng¹,

Wang

Shih

et al. 1987

American J Industrial Med

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Three workers from a color printing factory were admitted to community hospitals in 1985 with manifestations of acute hepatitis. One of the three had superimposed acute renal failure and pulmonary edema. An investigation was subsequently conducted at the plant to determine the etiology of the outbreak and the prevalence of liver disease among the remaining workers. Comprehensive medical evaluations were conducted, which included physical examinations, liver function tests, and serological screening for hepatitis. Seventeen of 25 workers from the plant had abnormal liver function tests 10 days after the outbreak, and a significant association was found between the presence of abnormal liver function tests and a history of recently having worked inside any of three rooms in which an interconnecting air conditioning system had been installed to cool the printing machines. After further investigation, it was determined that the incident occurred following inadvertent use of carbon tetrachloride to clean a pump in the printing machine. A simulation of the pump cleaning operation revealed ambient air levels of carbon tetrachloride of 300-500 ppm. Ultimately, it was concluded that the outbreak was in all likelihood due to the combined use of carbon tetrachloride and isopropyl alcohol in the cleaning operation. This outbreak underscores the importance of adopting appropriate industrial hygiene measures in a rapidly industrializing nation such as Taiwan.

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Enhanced Hepatic Microsomal Activity by Pretreatment of Rats with Acetone or Isopropanol

Cited by 50 publications

References 5 publications

Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat

Effect of a single oral dose of methanol, ethanol and propan-2-ol on the hepatic microsomal metabolism of foreign compounds in the rat

Activation of 3':5'-cyclic AMP-dependent protein kinase and induction of ornithine decarboxylase as early events in induction of mixed-function oxygenases.

Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan

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