Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs

Our plain-English summary of Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs, by J.M. Arif, S.G. Khan, M. Aslam, et al (Pharmacology & Toxicology, 1992).

The study

• Authors: J.M. Arif, S.G. Khan, M. Aslam, N. Mahmood, Q. Rahman
• Journal: Pharmacology & Toxicology
• Published: 1992;71(1):37-40
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In order to determine the pulmonary toxicity of kerosene and its ignition product (soot) in asbestos exposed subjects, the activities of phase I and phase II drug metabolizing enzymes in rat lungs after single intratracheal co-exposure to Indian chrysotile asbestos and kerosene or its soot and Indian chrysotile were assayed. Exposure to kerosene or its soot resulted in a significant increase in the level of microsomal cytochrome P-450 and the activity of P-450 dependent monooxygenase, benzo(a)pyrene hydroxylase, as well as in the activities of microsomal epoxide hydrase and cytosolic glutathione-S-transferase (GST). However, in chrysotile exposed animals a reverse pattern in these parameters was recorded. The co-exposure to chrysotile and kerosene or chrysotile and soot led to a significant depletion in cytochrome P-450 level and a decrease in the activities of benzo(a)pyrene hydroxylase, epoxide hydrase and GST when compared to kerosene and soot controls, respectively. These results suggest that asbestos by altering the pulmonary drug metabolizing enzyme system may increase the toxic potential of kerosene and its ignition product in the respiratory system.

In plain English

This was an animal experiment from the Industrial Toxicology Research Centre in Lucknow, India. Male albino rats received one dose into the windpipe of kerosene (0.05 ml), kerosene soot (5 mg), Indian chrysotile asbestos (5 mg), or chrysotile mixed with kerosene or soot, in corn oil. Controls received corn oil alone or no treatment. Lungs were examined 1, 4, 8 and 16 days later for enzymes that process foreign chemicals. Kerosene and soot alone raised lung cytochrome P-450, peaking on day 1. The article gives 363% (kerosene) and 461% (soot); its figure expresses P-450 as a percentage of control. Kerosene and soot also raised benzo(a)pyrene hydroxylase, epoxide hydrase and glutathione-S-transferase. Chrysotile alone lowered cytochrome P-450 on days 1, 4 and 8. Adding chrysotile to kerosene or soot lowered these enzymes compared with either alone. Day-1 epoxide hydrase averaged 2.28 with kerosene versus 0.84 with kerosene plus chrysotile, in fluorescence units per hour per mg protein (six rats each). The authors suggested that asbestos, by altering these enzymes, may increase the toxic potential of kerosene and soot in the lung.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (single intratracheal exposure of rats, lung enzyme measurements at several time points)
• Who was studied: Male albino rats weighing 120-150 g from the Industrial Toxicology Research Centre animal colony, Lucknow, India, divided into seven sub-groups; tables report means of six animals per group; killed 1, 4, 8 and 16 days after exposure
• Exposure: Single intratracheal dose in 1 ml corn oil of 0.05 ml commercial kerosene, 5 mg kerosene soot, 5 mg Indian chrysotile (fiber size below 30 micrometres), 5 mg chrysotile plus 0.05 ml kerosene, or 5 mg chrysotile plus 5 mg soot; controls received corn oil only or no treatment
• Main results:
  • In rats exposed to kerosene or soot alone, lung cytochrome P-450 was highest one day after exposure, reported as 363% for kerosene and 461% for soot (the figure expresses values as a percentage of control), and then gradually declined
  • In rats co-exposed to chrysotile with kerosene or with soot, cytochrome P-450 was significantly lower than in rats exposed to kerosene alone or soot alone
  • Chrysotile alone significantly decreased cytochrome P-450 on days 1, 4 and 8
  • Kerosene or soot induced benzo(a)pyrene hydroxylase and epoxide hydrase, and chrysotile prevented this induction
  • On day 1, mean epoxide hydrase activity was 2.28 in kerosene-treated rats, 0.84 in kerosene plus chrysotile-treated rats and 0.70 in untreated controls (fluorescence units per hour per mg protein, mean of six animals per group)
  • Glutathione-S-transferase showed a small but statistically significant increase on days 1, 4, 8 and 16 after kerosene or soot alone; co-exposure with chrysotile decreased the activities seen with kerosene or soot alone
• The authors' conclusion: The authors suggested that chrysotile asbestos, by diminishing the kerosene- or soot-induced phase I and phase II drug metabolizing enzymes, may increase their toxic potential in the lung, which could be additionally involved in the carcinogenic response induced by asbestos

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Glutathione (GSH).

Related studies

• Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system — J.M. Arif, S.G. Khan, et al. (1994)
• Garlic attenuates chrysotile-mediated pulmonary toxicity in rats by altering the phase I and phase II drug metabolizing enzyme system — M. Ameen, M.S. Musthapa, et al. (2003)
• Effect of kerosene and its soot on the chrysotile-mediated toxicity to the rat alveolar macrophages — J.M. Arif, S.G. Khan, et al. (1997)
• Kerosene soot genotoxicity: enhanced effect upon co-exposure with chrysotile asbestos in Syrian hamster embryo fibroblasts — M. Lohani, E. Dopp, et al. (2000)
• Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung — Q. Rahman, S.G. Khan, et al. (1990)
• Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins — Q. Rahman, N. Mahmood, et al. (1997)

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