Induction of microsomal drug metabolism in man and in the rat by exposure to petroleum.

Abstract

To determine the effect of petroleum exposure on the activity of hepatic mixed function oxidase enzymes, salivary elimination kinetics of antipyrine were determined in 19 petrol station attendants and compared with 19 controls. Antipyrine half life in petrol station attendants was shorter than in controls. Microsomal preparations (10 000 x g supernatants) were prepared from six male Porton rats exposed to petrol vapour (5 ppm at an air flow rate of 4 1/min for eight hours a day for three weeks) and six control rats maintained under the same conditions without exposure to petrol vapour. The rates of oxidative metabolism of antipyrine, aminopyrine, ethylmorphine, aniline, and benzo(a)pyrene were all increased by more than 45 0 in the petrol-exposed rats. The results indicate that petrol vapour is a moderately potent inducer of mixed function oxidase activity in rats, and that occupational exposure to petroleum may result in enhanced microsomal drug metabolism. posed to petroleum. A convenient method of assessing such induction entails the use of antipyrine as a metabolic probe combined with salivary sampling as a non-invasive procedure for sample collection.6In the present study the kinetics of antipyrine elimination were determined in petrol station attendants, and an attempt was made to correlate this with the degree of exposure to petrol, using urinary phenol output and blood and urinary lead concentrations as indices of exposure. In addition the inductive effect of petrol on microsomal drug metabolising enzyme activity in vitro was assessed in rats after three weeks' intermittent exposure to petrol vapour. Methods HUMAN STUDY SubjectsNineteen male employees at six metropolitan petrolvending stations participated in the study. All had worked as petrol pump attendants or garage mechanics, or both, for more than one year. They were aged (mean + SD, 28 ± 10), and they were not taking any medicine at the time of the study. On the morning of the third day of a five-anda-half-day working week, each subject ingested 91 on 7 June 2019 by guest. Protected by copyright.

Protective Effect of Vitamins C and E against Gasoline Vapors Induced Haematological and Biochemical Changes in Male Rats

“…In this study, there was a significant increase in the activities of serum ALP, ALT and AST following the exposure to gasoline vapor. Previous workers have also noted an increase in rat liver enzymes activities after chronic exposure to gasoline vapors [44][45][46][47]. In addition, it was revealed that the activities of ALT and AST elevated in gas station workers [48].…”

Jet fuel and liver function.

“…In 19 gas station attendants exposed to gasoline during conditions of work resembling those of our fuel-filling attendants, a significantly lower antipyrine half-time was found in comparison to that of 19 referents from a university staff and students. The study was weakened by its cross-sectional design and lack of information about host factors with known impact on antipyrine clearance (9).…”

“…Accordingly, our data indicate that jet fuel is an inducer of microsomal enzyme activity in man . Jet fuel is a mixture of aliphatic and aromatic hydro carbons closely related to white spirit and gasoline, both of which are inducers of microsomal enzyme ac-tivity in rats (9,11). In 19 gas station attendants exposed to gasoline during conditions of work resembling those of our fuel-filling attendants, a significantly lower antipyrine half-time was found in comparison to that of 19 referents from a university staff and students.…”

“…A recent study on man and rats has shown that gasoline, which is a mixture of aliphatic and aromatic hydrocarbons, is an inducer of microsomal enzyme activity as assessed by the widely used antipyrine test (9). Animal studies indicate that microsomal enzyme activity is changed by organic solvents in concentrations not high enough to cause elevations in conventional liver enzyme tests but nevertheless high enough to lead to alterations in the hepatic ultrastructure (7), a phenomenon which may be potentially harmful.…”

HPLC determination of caffeine and paraxanthine in urine: An assay for cytochrome P450 1A2 activity

“…Oral contraceptives and estrogen hormone replacement therapy have also been identified as inhibitors of the metabolic activity of P450 1A2 [11,15,19]. Individuals who are exposed to enzyme inducers or inhibitors in the workplace, such as anesthesiologists exposed to anesthetic chemicals in the operating room, gasoline station attendants exposed to high levels of petroleum, and greenhouse workers exposed to pesticides, may also exhibit altered P450 1A2 metabolic activity [20][21][22][23]. Beyond these environmental factors, age and gender have also been shown to affect P450 1A2 metabolic activity with children having higher activity than adults, and men having higher activity than women, though this latter observation is disputed [11,14,15,18,19].…”