Comparison of functional, biochemical, and morphometric alterations in the lungs of 4 rat strains and hamsters following repeated intratracheal instillation of crocidolite asbestos

Our plain-English summary of Comparison of functional, biochemical, and morphometric alterations in the lungs of 4 rat strains and hamsters following repeated intratracheal instillation of crocidolite asbestos, by D.J. Padilla-Carlin, D.L. Costa (Experimental Lung Research, 2011).

The study

• Authors: D.J. Padilla-Carlin, D.L. Costa
• Journal: Experimental Lung Research
• Published: 2011;37(4):212-26
• Read it: PubMed · Publisher

Abstract

Four rat strains and hamsters were exposed to 0.7 mg crocidolite asbestos/g lung once/week for 3 weeks by intratracheal instillation (IT). Pulmonary function, biochemistry, and morphometry were evaluated at 3 and 6 months after IT. Each rat strain, but not the hamster, exhibited elevated lung volumes. Quasistatic compliance in rats and hamsters was reduced 15%-40% and 25%-50%, respectively. Diffusing capacity for carbon monoxide was elevated in the rats, but in hamsters, it was reduced at both time points. Hydroxyproline was increased in the rat strains but not in hamsters. Lung protein/dry weight was not altered in most of the rat strains and in hamsters at both time points. The linear mean intercept value was increased in Fischer 344 (F344) rats (3 and 6 months) and Long Evans rats (6 months), whereas in hamsters only at 6 months. Surface area was unchanged in both species. Specific density for parenchymal tissue was reduced for F344 rats at both time points, but alveolar density values did not change overall relative to species and time. The correlated functional and morphological changes in the hamster appeared more consistent with human asbestosis. Divergent lung responses in different species and strains should be considered when selecting laboratory animal models for studies related to asbestos exposure.

In plain English

In this animal experiment, four strains of male rats (Sprague-Dawley, Fischer 344, Wistar, Long Evans Hooded) and Golden Syrian hamsters received crocidolite asbestos by intratracheal instillation, 0.7 mg per gram of lung once a week for three weeks, or saline as control; four animals from each exposed or control group were assessed at each time point. Lung function, lung biochemistry and morphometry were measured 3 and 6 months after the last instillation. All rat strains showed increased total lung capacity and functional residual capacity at both time points, while hamsters did not. Forced expiratory flow at 25% of forced vital capacity fell in every group, ranging at 3 months from about 85% below control in F344 rats to about 45% below control in hamsters. Diffusing capacity for carbon monoxide rose in the rat strains but was significantly reduced in hamsters. Absolute hydroxyproline rose in exposed rats and hamsters alike, but the percentage change from controls in hydroxyproline per lung dry weight was higher in all rat strains than in hamsters. The authors concluded that the hamster showed a restrictive pulmonary phenotype resembling human asbestosis, unlike the rats.

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: controlled animal experiment comparing 4 rat strains and hamsters after repeated intratracheal instillation, with assessment at 3 and 6 months
• Who was studied: Male specific pathogen-free animals bought at about 8 weeks of age: Sprague-Dawley, Fischer 344, Wistar and Long Evans Hooded rats and Golden Syrian hamsters; lung function was assessed in 4 animals from each exposed or control group at each of the 3- and 6-month time points, with fewer animals for some morphometric measurements; study conducted at Brookhaven National Laboratory
• Exposure: Crocidolite asbestos (NIEHS standard; mean width 0.27 micrometres, mean length 10 micrometres) suspended in saline, 0.7 mg per gram of lung per instillation, three weekly instillations, total 2.1 mg per gram of lung; controls received sterile saline
• Main results:
  • All four rat strains, but not hamsters, had increased total lung capacity and functional residual capacity at 3 and 6 months
  • Forced expiratory flow at 25% of forced vital capacity was decreased in all strains and species; at 3 months the percent change from controls ranged from about 85% below control in F344 rats to about 45% below control in hamsters, with no statistically significant differences between strains or species
  • Diffusing capacity for carbon monoxide increased in the exposed rat strains but was significantly reduced in exposed hamsters at both 3 and 6 months
  • At 6 months the fall in quasistatic compliance (chord slope) was larger in hamsters (about 45.6% below control, standard error 15.6%) than in Wistar rats (about 5.5% below control) or Long Evans rats (about 3.9% below control)
  • Expressed per lung dry weight as percent change from control, hydroxyproline (index of total collagen) and elastin were higher in all rat strains than in hamsters at 3 and 6 months
  • In absolute terms, lung mass and all biochemical variables rose in exposed hamsters, but when normalized to lung dry weight these variables did not differ from controls at either time point
  • Alveolar mean linear intercept was increased in F344 rats at 3 and 6 months, in Long Evans rats at 6 months and in hamsters only at 6 months; internal surface area was unaffected in all groups; specific density for parenchymal tissue was reduced only in F344 rats
  • Absolute right lung dry weight rose by roughly 25 to 75 percent over controls across the rat strains
• The authors' conclusion: The authors concluded that the hamster showed a restrictive pulmonary phenotype suggesting a physiologic response analogous to human asbestosis, and that species and strain differences in lung response should be taken into account when choosing animal models
• Limitations the authors state:
  • The authors note the interpretive problems of using repeated low-dose intratracheal instillation rather than single instillation or inhalation, possible fiber agglomeration in the airways, and possible lung overload
  • Overload could not be excluded in an intratracheal instillation study
  • Saline, rather than an inert insoluble particle, was used as the control, so fiber-specific effects could not be fully separated
  • The Wistar 3-month group had few animals available for morphometric measurement because of fixation problems
  • The authors state that inhalation exposure and several doses would ideally have been used

Topics

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

Medical terms in this study, explained in our Lexicon: Crocidolite, Diffusing Capacity (DLCO), Asbestos Exposure.

Related studies

• Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos — R. Yamaguchi, T. Hirano, et al. (1999)
• Functional and biochemical effects on rat lung following instillation of crocidolite and chrysotile asbestos — S. Hirano, M. Ono, et al. (1988)
• Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene — V.J. Feron, P.M. Scherrenberg, et al. (1985)
• Macrophage phagocytic activity and cell phagocytic capacity following intratracheal instillation of a comixture of asbestos fibers — I. Trosic, M. Matausic-Pisl, et al. (1995)
• The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• Scanning electron microscopical investigations of broncho-alveolar casts after intratracheal asbestos fibre instillation — B. Voss, T. Kerenyi, et al. (2000)

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