Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles

Our plain-English summary of Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles, by K.E. Driscoll, J.M. Carter, P.J. Borm (Inhalation Toxicology, 2002).

The study

• Authors: K.E. Driscoll, J.M. Carter, P.J. Borm
• Journal: Inhalation Toxicology
• Published: 2002;14(1):101-18
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This narrative review examined how antioxidant defenses of the respiratory tract relate to the toxicity of inhaled fibrous and nonfibrous particles, and what species differences in these defenses might mean for risk assessment. The authors described the lung's enzymatic and nonenzymatic antioxidants. They summarized in vitro, animal and human studies indicating that particles act partly through reactive oxygen species, including crystalline silica, crocidolite and chrysotile asbestos, ambient air particles, hard metal and combustion particles. They reviewed evidence that particle exposure induced antioxidant enzymes such as manganese superoxide dismutase, that antioxidants reduced asbestos effects in cultured cells and in rats, and studies of antioxidants in coal miners. Comparative studies reported markedly lower lung catalase in rats than in other species, and one found antioxidant enzyme levels most similar in humans and hamsters. The authors also presented data in which rats and hamsters received quartz by intratracheal instillation at 0.2, 2 or 20 mg/kg and were examined 7 days later. Hamsters had higher basal lung catalase and metallothionein and induced them more strongly. Rats showed greater release of reactive oxygen and nitrogen species, more tissue injury and more cell proliferation. Similar findings were reported for carbon black. The authors concluded that the rat may be an especially sensitive species to oxidative injury from particles and that understanding antioxidant capacity could help extrapolation from animals to humans.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This article was a review, not a new study. The authors summarized published laboratory, animal and human research on how the lung's antioxidant defenses relate to the harm caused by inhaled particles, including asbestos (crocidolite, chrysotile, amosite), crystalline silica and other dusts. In studies they reviewed, crocidolite and chrysotile raised the antioxidant enzyme superoxide dismutase in hamster airway cells. Treating rats with a modified form of the enzyme catalase reduced lung inflammation and fibrosis after three weeks of crocidolite inhalation. Another reviewed study found no link between how harmful a panel of fibers, including amosite, was in animals and how much the fibers used up antioxidants in laboratory tests. One study found markedly lower lung catalase in rats than in humans, hamsters and baboons. The authors also presented data from their own earlier study of quartz given to rats and hamsters. Hamsters had higher and more strongly increased antioxidants, while rats showed more lung injury and cell proliferation. The authors concluded that antioxidant changes are a potential sign that a material acts through oxidative mechanisms.

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: narrative review of published in vitro, animal and human studies, including data from the authors' own earlier animal studies
• Who was studied: No new subjects. The review covered cell studies, animal studies (rats, mice, hamsters, guinea pigs, monkeys, baboons and others) and human studies, mostly of coal miners. It also presented the authors' earlier study (Driscoll & Carter, 2000) of rats and hamsters given quartz at 0.2, 2 or 20 mg/kg by intratracheal instillation and examined 7 days later.
• Exposure: Fibrous and nonfibrous particles. These included asbestos (crocidolite, chrysotile, amosite and, in cell studies, tremolite), the mineral fiber erionite, crystalline silica (quartz, cristobalite), man-made fibers, diesel exhaust, carbon black, residual oil fly ash, ultrafine titanium dioxide, and cobalt/hard metal.
• Main results:
  • In a reviewed study (Mossman et al., 1986), crocidolite and chrysotile asbestos fibers increased superoxide dismutase activity in hamster tracheal epithelial cells in vitro.
  • In a reviewed study (Mossman et al., 1990), treating rats with PEG-catalase reduced lung inflammation and fibrosis linked to a 3-week crocidolite inhalation.
  • In a reviewed study (Brown et al., 2000), there was no relationship between how harmful a panel of fibers (including amosite) was in animals and how much the fibers depleted glutathione or ascorbate in vitro.
  • In a reviewed study of humans, hamsters, baboons and rats (Bryan and Jenkinson, 1987), rats had markedly lower lung catalase than the other species.
  • A reviewed study (Hanaoka et al., 1993) did not find differences in oxidative DNA damage markers in blood cells between subjects with and without asbestosis.
  • In the authors' earlier quartz study, catalase increased in both rats and hamsters after exposure, with a markedly greater change in hamsters.
  • In the same quartz study, lung metallothionein had higher basal levels in hamsters and was induced to a greater extent in hamsters than in rats.
  • In the same quartz study, rats showed greater lung tissue injury and cell proliferation than hamsters.
• The authors' conclusion: The authors concluded that expression of antioxidants is a potential indicator that an inhaled material acts, at least in part, through oxidative mechanisms.
• Limitations the authors state:
  • Evidence from living animals that oxidative stress drives particle toxicity exists for only a few materials.
  • Findings on antioxidant defenses other than Mn-SOD and glutathione are variable, possibly because of differences between in vitro and in vivo models and study designs.
  • Antioxidant defenses can also be altered by diet, smoking and other acquired factors.
  • Understanding of the relationships between particle exposure, antioxidant mechanisms and susceptibility is at an early stage.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Crystalline, Crocidolite, Chrysotile, Superoxide.

Related studies

• Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells — K. Järvinen, P. Pietarinen-Runtti, et al. (2000)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 3: Depletion of antioxidant defenses — E. Gazzano, C. Riganti, et al. (2005)
• Impact of acute and subchronic asbestos exposure on some parameters of antioxidant defense system and lung tissue injury — A. Kaiglová, Z. Kováciková, et al. (1999)
• Oxidative and cytotoxic stress induced by inorganic granular and fibrous particles — S. Helmig, D. Walter, et al. (2018)
• Toxicokinetics and effects of fibrous and nonfibrous particles — G. Oberdörster (2002)
• Ferruginous bodies: implications in the mechanism of fiber and particle toxicity — A.J. Ghio, A. Churg, et al. (2004)

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