Regulation of antioxidant enzymes in lung after oxidant injury

Our plain-English summary of Regulation of antioxidant enzymes in lung after oxidant injury, by T. Quinlan, S. Spivack, B.T. Mossman (Environmental Health Perspectives, 1994).

The study

• Authors: T. Quinlan, S. Spivack, B.T. Mossman
• Journal: Environmental Health Perspectives
• Published: 1994;102 Suppl 2(Suppl 2):79-87
• Type of article: Review
• Cited by: 100 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Studies have implicated active oxygen species (AOS) in the pathogenesis of various lung diseases. Many chemical and physical agents in the environment are potent generators of AOS, including ozone, hyperoxia, mineral dusts, paraquat, etc. These agents produce AOS by different mechanisms, but frequently the lung is the primary target of toxicity, and exposure results in damage to lung tissue to varying degrees. The lung has developed defenses to AOS-mediated damage, which include antioxidant enzymes, the superoxide dismutases [copper-zinc (CuZnSOD) and manganese-containing (MnSOD)], catalase, and glutathione peroxidase (GPX). In this review, antioxidant defenses to environmental stresses in the lung as well as in isolated pulmonary cells following exposure to a number of different oxidants, are summarized. Each oxidant appears to induce a different pattern of antioxidant enzyme response in the lung, although some common trends, i.e., induction of MnSOD following oxidants inducing inflammation or pulmonary fibrosis, in responses to oxidants occur. Responses may vary between the different cell types in the lung as a function of cell-cycle or other factors. Increases in MnSOD mRNA or immunoreactive protein in response to certain oxidants may serve as a biomarker of AOS-mediated damage in the lung.

In plain English

This article was a review, not a new study. The authors summarized published research on how the lung's antioxidant enzymes (the superoxide dismutases MnSOD and CuZnSOD, catalase and glutathione peroxidase) respond to agents that produce active oxygen species. These agents were ozone, high oxygen (hyperoxia), mineral dusts, the herbicide paraquat, cigarette smoke and the drug bleomycin. For asbestos, the reviewed studies reported that rats inhaling crocidolite at 7-10 mg/m3 showed increased activity of all measured antioxidant enzymes in lung tissue. MnSOD messenger RNA rose most, peaking at 6 to 9 days and declining to near normal levels by 14 days after exposure. After cristobalite silica, MnSOD messenger RNA remained elevated at 14 days. Cultured human mesothelial cells exposed to crocidolite or chrysotile showed 2- to 3-fold increases in MnSOD messenger RNA. In rats exposed to asbestos, the catalase dose needed to reduce lung damage was much greater than the roughly 2-fold enzyme increases seen after asbestos exposure. The authors concluded that evidence implicates antioxidant enzymes in lung defense. They noted that increased MnSOD was common to several stresses and may serve as a biomarker of oxidant damage.

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 laboratory and animal studies
• Who was studied: published studies of lung tissue and isolated lung cells (mostly rats, also mice, hamsters, Japanese quail, monkeys and cultured human cells) exposed to oxidants
• Exposure: ozone, hyperoxia, mineral dusts (crocidolite and chrysotile asbestos, cristobalite silica), paraquat, cigarette smoke and bleomycin
• Main results:
  • In reviewed rat studies, inhalation of crocidolite at 7-10 mg/m3 increased the activity of all measured antioxidant enzymes in lung tissue
  • In these crocidolite-exposed rats, MnSOD messenger RNA peaked at 6 to 9 days and declined to near normal at 14 days after exposure
  • In rats exposed to cristobalite silica, MnSOD messenger RNA was still elevated 14 days after exposure ended
  • In rats exposed to mineral dust, increases of MnSOD in type II epithelial cells matched 2-fold or greater increases of the protein in whole lung
  • In cultured human mesothelial cells, crocidolite or chrysotile asbestos produced 2- to 3-fold increases in MnSOD messenger RNA
  • In rats exposed to asbestos, the catalase dose needed to reduce lung damage far exceeded the roughly 2-fold enzyme increases the lungs produced on their own
  • Across hyperoxia, paraquat and mineral dusts, a shared response was increased MnSOD expression
  • The authors wrote that increases in MnSOD messenger RNA or protein may serve as a biomarker of oxidant damage in the lung
• The authors' conclusion: The authors concluded that evidence implicates antioxidant enzymes as components of lung defense after oxidative stress
• Limitations the authors state:
  • The review left out other oxidant-responsive proteins such as heme oxygenase, metallothionein and heat shock proteins
  • The authors stated that a protective role of these enzymes against ozone is presumed but unproven

Topics

Medical terms in this study, explained in our Lexicon: Superoxide, Glutathione (GSH), Inflammation, Pulmonary Fibrosis, Biomarker.

Related studies

• 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)
• Oxidants and signaling by mitogen-activated protein kinases in lung epithelium — B.T. Mossman, K.M. Lounsbury, et al. (2006)
• The protective role of antioxidants in the defence against ROS/RNS-mediated environmental pollution — B. Poljšak, R. Fink (2014)
• Comparative study of antioxidant properties and cytoprotective activity of flavonoids — A.I. Potapovich, V.A. Kostyuk (2003)
• Antioxidant defense mechanisms and the toxicity of fibrous and nonfibrous particles — K.E. Driscoll, J.M. Carter, et al. (2002)
• Mesothelial cell proliferation: a nonspecific response to lung injury associated with fibrosis — I.Y. Adamson, J. Bakowska, et al. (1994)

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