Chronic physical activity: Hepatic hypertrophy and increased total biotransformation enzyme activity

Yiamouyiannis, Carmen A.; Sanders, Ruth A.; Watkins, John B.; Martin, Bruce

doi:10.1016/0006-2952(92)90045-k

Cited by 24 publications

(12 citation statements)

References 27 publications

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“…At a higher styrene oxide concentration (100 pg/g of blood) at 37°C the half-life increased to 41 min, again suggesting a saturable removal process. At a higher styrene oxide concentration (100 pg/g of blood) at 37°C the half-life increased to 41 min, again suggesting a saturable removal process.…”

Section: B Analysis Of Styrene and Metabolites In Bloodmentioning

confidence: 95%

Review of the Metabolic Fate of Styrene

Sumner

Fennell

1994

Critical Reviews in Toxicology

181

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Styrene and styrene oxide have been implicated as reproductive toxicants, neurotoxicants, or carcinogens in vivo or in vitro. The use of these chemicals in the manufacture of plastics and polymers and in the boat-building industry has raised concerns related to the risk associated with human exposure. This review describes the literature to date on the metabolic fate of styrene and styrene oxide in laboratory animals and in humans. Many studies have been conducted to assess the metabolic fate of styrene in rats, and investigations on the metabolism of styrene in humans have been of considerable interest. Limited research has been done to assess metabolism in the mouse. The metabolism of styrene to styrene oxide and further conversion to styrene glycol (via epoxide hydrolase), mandelic acid, and phenylglyoxylic acid has been given considerable attention, and is considered to be the major pathway of activation and detoxication for humans. While the hydrolysis of styrene oxide to styrene glycol historically has been the favored pathway for the rat, studies in more recent years have indicated that glutathione conjugation also is a viable and significant pathway for both the rat and the mouse. This pathway has not been established in humans. Mandelic acid and phenylglyoxylic acid have been used as urinary markers of exposure in humans exposed to styrene. Extensive investigations have been conducted on the kinetics of styrene and styrene oxide in rodents. In people, the kinetics of styrene and styrene oxide in the blood of occupationally exposed workers and volunteers have been determined. Pharmacokinetic models developed in the last decade have become increasingly complex, with the most recent physiologically based model describing the kinetics of styrene and styrene oxide. This model shows pronounced species differences in sensitivity coefficients for styrene or styrene oxide between mice, rats, and humans, where mice are the more sensitive species to the Vmax for both epoxide hydrolase and monooxygenase. This result is particularly interesting in light of the recent findings of extensive mortality and hepatotoxicity for mice exposed to relatively low levels of styrene (250 to 500 ppm), while rats and humans exhibit only nasal and eye irritations at exposure concentrations well above 500 ppm.

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Section: B Analysis Of Styrene and Metabolites In Bloodmentioning

confidence: 95%

Review of the Metabolic Fate of Styrene

Sumner

Fennell

1994

Critical Reviews in Toxicology

181

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“…Week Exercise Training Group Protocol [21]. The 8 week exercise training protocol is presented in Table 2.…”

Section: Eightmentioning

confidence: 99%

“…Exercise training is defined by repetitive exercise over an extended period of time. Exercise training may modify hepatic drug metabolism by altering enzyme levels in the liver [16][17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

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The influence of moderate and chronic exercise training on the pharmacokinetics of procainamide and N-acetylprocainamide

Eddington

Adekoya

Kharidia

1998

Biopharm. Drug Dispos.

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The effect of moderate and prolonged exercise on the disposition and metabolism of drugs has not been extensively examined. The present study examined the effect of exercise training on the pharmacokinetics of procainamide and its active metabolite, N‐acetylprocainamide. Male Sprague Dawley rats were randomly assigned to three testing groups: (1) sedentary, (2) 4 weeks of exercise training and (3) 8 weeks of exercise training. Treadmill speed and exercise duration were gradually increased, reaching a final rate of 24 m min−1 for an hour by the end of the 4‐week or 8‐week period. Sedentary and exercise trained rats received a single i.p. dose of procainamide (100 mg kg−1). Serial blood samples were collected over a 10 h period and plasma samples were analysed by an UV‐HPLC method. Noncompartmental analysis was performed to estimate the pharmacokinetic parameters. The t1/2 of procainamide was significantly (p <0.05) higher in the 8 week exercise group (331 min) as compared to the sedentary group (77 min). In addition, there was a significant reduction in the amount of N‐acetylprocainamide formed after 8 weeks of exercise (AUCNAPA=739 ng mL−1 min−1). Results of this study suggest that prolonged exercise (8 weeks of training) alters the pharmacokinetics of procainamide by modifying the amount of active metabolite formed. © 1998 John Wiley & Sons, Ltd.

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“…However, little information is available on the protective role of chronic exercise against the toxins and free radicals generated through metabolism of various pharmacological agents. Chronic exercise may alter the pharmacokinetic characteristics of some drugs and ethanol (30), and increase drug metabolism (31), detoxicant capacity of the liver (25), and enhance antioxidant mechanisms altering specific components of the endogenous antioxidant system (25). Based on these observations, it is conceivable to postulate that chronic exercise may alter the toxic effects of drugs on tissues.…”

mentioning

confidence: 97%