Early and delayed effects of naturally occurring asbestos on serum biomarkers of inflammation and metabolism

Our plain-English summary of Early and delayed effects of naturally occurring asbestos on serum biomarkers of inflammation and metabolism, by U.P. Kodavanti, D. Andrews, M.C. Schladweiler, et al (Journal of Toxicology and Environmental Health. Part a, 2014).

The study

• Authors: U.P. Kodavanti, D. Andrews, M.C. Schladweiler, S.H. Gavett, D.E. Dodd, J.M. Cyphert
• Journal: Journal of Toxicology and Environmental Health. Part a
• Published: 2014;77(17):1024-39
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Studies recently showed that intratracheal (IT) instillation of Libby amphibole (LA) increases circulating acute-phase proteins (APP; α-2 macroglobulin, A2M; and α-1 acid glycoprotein, AGP) and inflammatory biomarkers (osteopontin and lipocalin) in rats. In this study, objectives were to (1) compare changes in biomarkers of rats after instillation of different naturally occurring asbestos (NOA) minerals including LA, Sumas Mountain chrysotile (SM), El Dorado Hills tremolite (ED), and Ontario ferroactinolite cleavage fragments (ON), and (2) examine biomarkers after subchronic LA or amosite inhalation exposure. Rat-respirable fractions (aerodynamic diameter approximately 2.5 μm) prepared by water elutriation were delivered via a single IT instillation at doses of 0, 0.5, and 1.5 mg/rat in male F344 rats. Nose-only inhalation exposures were performed at 0, 1, 3.3, and 10 mg/m(3) for LA and at 3.3 mg /m(3) for amosite, 6h/d, 5 d/wk for 13 wk. Inflammation, metabolic syndrome, and cancer biomarkers were analyzed in the serum for up to 18 mo. IT instillation of some asbestos materials significantly increased serum AGP and A2M but to a varying degree (SM = LA > ON = ED). Numerical increases in interleukin (IL)-6 and osteopontin occurred in rats instilled with SM. SM and ED also elevated leptin and insulin at 15 mo, suggesting potential metabolic effects. LA inhalation tended to raise A2M at d 1 but not cytokines. Serum mesothelin appeared to elevate after 18 mo of LA inhalation. These results suggest that the lung injury induced by high levels of asbestos materials may be associated with systemic inflammatory changes and predisposition to insulin resistance.

In plain English

This animal study re-tested blood serum from two earlier toxicology experiments in male F344 rats. In one, rats got a single dose (0.5 or 1.5 mg per rat) of Libby amphibole, Sumas Mountain chrysotile, El Dorado Hills tremolite or Ontario ferroactinolite cleavage fragments, placed directly into the windpipe. In the other, rats breathed Libby amphibole (1, 3.3 or 10 mg/m3) or UICC amosite (3.3 mg/m3) 6 hours a day, 5 days a week, for 13 weeks. Groups of six to eight rats were tested at times up to 15 or 18 months. One day after a single dose, Libby amphibole sharply raised two inflammation-related 'acute-phase' blood proteins. The chrysotile produced a similar rise. By 3 months the rises were gone. At 15 months, insulin was raised after the chrysotile, tremolite and ferroactinolite. After inhalation, mesothelin, a mesothelioma marker, tended higher at 18 months with the highest Libby amphibole level, but not statistically significantly. The authors concluded that the acute-phase rises were related to lung inflammation and are not specific to asbestos, and that more experiments are needed on metabolic effects.

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: retrospective analysis of stored serum samples from two rat toxicology studies, one using a single intratracheal (IT) instillation and one using 13-week (subchronic) nose-only inhalation
• Who was studied: Healthy male F344 rats from Charles River Laboratories. Rats in the instillation study were 11 to 12 weeks old and weighed 215 to 250 g. Rats in the inhalation study were 10 weeks old and weighed about 200 g. Serum came from six to eight rats per group, with separate groups for each time point and exposure. The instillation study was run at a U.S. EPA laboratory and the inhalation study at the Hamner Institutes for Health Sciences in North Carolina.
• Exposure: Instillation study: a single dose of 0 (dispersion medium only), 0.5 or 1.5 mg per rat of water-elutriated, rat-respirable fractions (under 2.5 micrometres) of four naturally occurring asbestos materials: Libby amphibole (LA), Ontario ferroactinolite cleavage fragments (ON), Sumas Mountain chrysotile (SM) and El Dorado Hills tremolite (ED). Serum was sampled at 1 day, 3 months and 15 months. Inhalation study: filtered air, raw LA at 1, 3.3 or 10 mg/m3, or UICC amosite at 3.3 mg/m3, for 6 hours a day, 5 days a week, for 13 weeks. Serum was sampled 1 day, 1 month, 3 months and 18 months after exposure.
• Main results:
  • In the instillation study, LA markedly raised the acute-phase proteins alpha-1 acid glycoprotein (AGP) and alpha-2 macroglobulin (A2M) at 1 day.
  • SM caused a similar rise. ED and ON produced no significant change in either protein.
  • The day-1 increases in AGP and A2M after instillation were no longer seen at 3 months.
  • At 15 months after instillation, AGP was significantly raised in rats given ON at 1.5 mg/rat, SM at 0.5 mg/rat and ED at 0.5 mg/rat. The authors called the biological significance of these increases questionable.
  • In the inhalation study, A2M was significantly raised at 1 day in rats exposed to the highest LA level.
  • A2M was significantly higher in amosite-exposed rats at 18 months.
  • Serum IL-6 did not change significantly in the inhalation study.
  • Osteopontin rose 1 day after instillation of SM.
  • At 15 months after instillation, ON, SM and ED, but not LA, were associated with a marked rise in serum insulin.
  • At 15 months after instillation, leptin was markedly raised in rats given SM or ED.
  • Serum adiponectin did not change significantly with any fiber in either study.
  • Mesothelin tended to be higher 18 months after inhalation of the highest LA level, but this was not statistically significant.
• The authors' conclusion: The authors concluded that a single instillation of these naturally occurring asbestos materials raised circulating acute-phase proteins in a reversible way, and that these rises were related to how much lung inflammation each material produced.
• Limitations the authors state:
  • The instillation doses were high and not likely to be met in a short inhalation exposure near a mining area.
  • Many of the biomarker changes reflect a response to lung injury and are not specific to asbestos.
  • The meaning of the insulin and leptin changes, and what causes them, could not be determined because they occurred only at the 15-month time point.
  • More experiments are needed to determine the metabolic effects of asbestos.
  • The predictive value of the non-significant mesothelin rise is unclear.
  • The study could not establish whether osteopontin is useful as a cancer marker.
  • IL-6 was not measured at 18 months in the inhalation study.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Libby vermiculite mine, Montana

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: naturally occurring asbestos (NOA), Biomarker, Inflammation, Libby amphiboles, Glycoprotein, Osteopontin, Chrysotile, El Dorado Hills.

Related studies

• Acute phase response, inflammation and metabolic syndrome biomarkers of Libby asbestos exposure — J.H. Shannahan, O. Alzate, et al. (2012)
• Long-term toxicity of naturally occurring asbestos in male Fischer 344 rats — J.M. Cyphert, M.A. McGee, et al. (2016)
• Sumas Mountain chrysotile induces greater lung fibrosis in Fischer344 rats than Libby amphibole, El Dorado tremolite, and Ontario ferroactinolite — J.M. Cyphert, A. Nyska, et al. (2012)
• Serum biomarkers in patients with mesothelioma and pleural plaques and healthy subjects exposed to naturally occurring asbestos — M. Bayram, I. Dongel, et al. (2014)
• The role of iron in Libby amphibole-induced acute lung injury and inflammation — J.H. Shannahan, A.J. Ghio, et al. (2011)
• Long-term response of rats to single intratracheal exposure of Libby amphibole or amosite — J.M. Cyphert, D.J. Padilla-Carlin, et al. (2012)

Browse more research in Journal of Toxicology and Environmental Health. Part a, or return to medical research.