Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system

Our plain-English summary of Effect of coexposure to asbestos and kerosene soot on pulmonary drug-metabolizing enzyme system, by J.M. Arif, S.G. Khan, N. Mahmood, et al (Environmental Health Perspectives, 1994).

The study

• Authors: J.M. Arif, S.G. Khan, N. Mahmood, M. Aslam, Q. Rahman
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 5(Suppl 5):181-3
• Cited by: 10 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

This article reports the effect of coexposure to Indian chrysotile asbestos (5 mg/rat) and kerosene soot (5 mg/rat) on the pulmonary phase I and phase II drug-metabolizing enzymes 1, 4, 8, 16, 30, 90, and 150 days after a single intratracheal inoculation. Exposure to soot resulted in a significant induction of the pulmonary microsomal cytochrome P450 and the activity of dependent monooxygenase, benzo(a)pyrene (B[a]P) hydroxylase, and epoxide hydrase at all time intervals. On the other hand, the cytosolic glutathione S-transferase (GST) activity was induced at days 1, 4, 8, 16, and 30 after exposure, followed by inhibition in the enzyme activity. In contrast, chrysotile exposure depleted cytochrome P450, B[a]P hydroxylase, epoxide hydrase, and GST at initial stages, while all these parameters except GST were induced at later stages. However, coexposure to chrysotile and soot led to a significant inhibition in the cytochrome P450 levels, activities of B[a]P hydroxylase, epoxide hydrase, and GST at initial stages of exposure. At advanced stages, however, an additional increase in cytochrome P450, B[a]P hydroxylase, and epoxide hydrase but a decrease in GST was observed. These results clearly show that the intratracheal coexposure to high levels of asbestos and kerosene soot alters the metabolic activity of the lung, which is turn may retain toxins in the system for a longer period, resulting in adverse pathological disorders.

In plain English

This was an animal experiment from the Industrial Toxicology Research Center in Lucknow, India. The authors noted that many Indian asbestos factory workers use kerosene as a household fuel. Male albino rats were split into four groups. One group got a single 5 mg dose of kerosene soot placed into the windpipe (intratracheally) in corn oil. A second got 5 mg of Indian chrysotile asbestos, a third got both, and controls got corn oil alone. Six rats per group were killed at 1, 4, 8, 16, 30, 90 and 150 days, and lung enzymes that process foreign chemicals were measured. Soot alone raised cytochrome P450 at every time point, most on day 1. Chrysotile alone lowered it on days 1 and 4 and raised it on days 30, 90 and 150. With both exposures, P450 was lower than with soot alone up to day 16 and higher than soot alone later. Two other enzymes followed a similar pattern. The authors concluded that chrysotile together with soot alters these lung enzymes, which may lead to retention of toxic compounds.

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 (rats given a single intratracheal dose, killed at set time points)
• Who was studied: Male albino rats (120-150 g) in four groups (soot, chrysotile, chrysotile plus soot, corn-oil controls), six animals per group at each of seven time points; Industrial Toxicology Research Center, Lucknow, India
• Exposure: Single intratracheal inoculation of 5 mg Indian chrysotile asbestos, 5 mg kerosene soot (made by burning commercial kerosene in a pressure stove under kitchen-like conditions), or both, each in 1 ml corn oil; controls received 1 ml corn oil only
• Main results:
  • Soot alone significantly increased lung cytochrome P450 at all seven time points. The increase was largest at day 1, about 570% (Table 1 means: 1.31 versus 0.23 nmole per mg protein in controls), and then gradually declined.
  • Chrysotile alone significantly lowered lung cytochrome P450 on days 1 and 4 only, and increased it at 30, 90 and 150 days
  • In rats given both chrysotile and soot, cytochrome P450 was depleted up to 16 days after exposure and significantly increased at longer periods, compared with soot alone
  • In rats given both chrysotile and soot, cytochrome P450 in lung microsomes was higher than with chrysotile alone
  • Two other enzymes, benzo[a]pyrene hydroxylase and epoxide hydrase, followed a pattern similar to cytochrome P450
  • Glutathione S-transferase (GST) changed as follows. With soot alone, it rose slightly but significantly on days 1, 4, 8 and 30 and was inhibited on days 90 and 150. With chrysotile alone, it was significantly inhibited at all time intervals. With both exposures, it was lower than with soot alone and, up to 30 days, higher than with chrysotile alone.
• The authors' conclusion: The authors concluded that in rats, chrysotile together with kerosene soot influences the lung's clearance mechanism by altering drug-metabolizing enzymes. They wrote that this results in retention of toxic compounds, which may lead to multiple hits over time causing neoplastic progression.
• Limitations the authors state:
  • The authors stated that the reason for the reversed pattern (rising cytochrome P450) in the later stages after exposure is not clear

Topics

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

Related studies

• Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs — J.M. Arif, S.G. Khan, et al. (1992)
• Kerosene soot genotoxicity: enhanced effect upon co-exposure with chrysotile asbestos in Syrian hamster embryo fibroblasts — M. Lohani, E. Dopp, et al. (2000)
• 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)
• Production of reactive oxygen intermediates by human macrophages exposed to soot particles and asbestos fibers and increase in NF-kappa B p50/p105 mRNA — R. Oettinger, K. Drumm, et al. (1999)
• 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)

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