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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Cancer chemotherapy and pharmacology 19 (1987), S. 213-220 
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of multiple doses of doxorubicin (DXR) on hematocrit and plasma levels of prostaglandins (PG), thromboxane B2 (TxB2) total lipid, esterfied and free fatty acids, and proteins were investigated in male rats. The rats received DXR (2mg/kg) or vehicle weekly by the subcutaneous route for 2, 4, 8, and 13 weeks and were killed 1 week after their last dose. Another group of rats treated for 13 weeks was sacrificed at 19 weeks, 6 weeks after the last dose. No changes in hematocrit or plasma after the last dose. No changes in hematocrit or plasma PG, TxB2, or total levels of fatty acids were noted between control and DXR-treated rats at either 3, 5, or 9 weeks. The hematocrit was slightly depressed from control levels at 14 and 19 weeks. Plasma PGE, PGF2α, and TxB2 were elevated over control levels at 14 and 19 weeks. Plasma 6-keto-PGF1α was increased over the control level only at 19 weeks. Total plasma lipid and esterified fatty acids were highly elevated over control levels at 14 and 19 weeks. Plasma free arachidonic acid was elevated over control levels at 14 and 19 weeks, while levels of other free fatty acids were unchanged. Plasma protein levels were slightly depressed from control levels at 3, 9, and 14 weeks. Elevations of plasma free arachidonic acid, PG, TxB2, esterified fatty acids, and total lipid might be involved in cardiotoxicity and nephrotoxicity found with chronic administration of DXR.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Keywords: tracheal epithelial cells ; air-interfaced culture ; ion transport ; drug transport ; permeability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. The objective of this study was to investigate how culture conditions would affect the morphological, functional, and permeability characteristics of rabbit tracheal epithelial cell layers being considered for drug transport studies. Methods. Rabbit tracheocytes were isolated by protease treatment and plated onto collagen-treated permeable supports at 1.3 × 106 cells/cm2. After 24 hr, cell layers were cultured either air-interfaced (AIC) on their apical surface or under conventional liquid covered conditions (LCC). Results. Scanning electron microscopy revealed mature cilia in AIC cell layers and ciliated cells denuded of cilia in LCC cell layers. Compared with LCC, AIC cell layers (n = 20) achieved a significantly higher peak equivalent short-circuit current (74.1 ± 6.5 vs. 51.6 ± 3.4 µA/cm2), a higher potential difference (70.9 ± 2.8 vs. 60.5 ± 3.0 mV), and a lower peak transepithelial electrical resistance (1.1 ± 0.03 vs. 1.5 ± 0.02 kohms,cm2). About 70% of the short-circuit current in AIC was amiloride-sensitive whereas 〈10% was furosemide-sensitive, similar to that found in native tissue. The corresponding values in LCC were 50% and 46%. The permeability of both AIC and LCC to lipophilic solutes (dexamethasone and propranolol) was similar, whereas the permeability of hydrophilic solutes (mannitol, sucrose, and albuterol) in AIC was only half that in LCC. Conclusions. Given the striking similarity in morphological and functional characteristics of the AIC to those in the in vivo situation, the AIC is favored as an in vitro model for future drug transport studies.
    Type of Medium: Electronic Resource
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