title: Accumulation of pigment granules in lacrymal gland epithelium in practolol-treated beagle dogs.
abstract: A 6-month oral toxicity test of practolol was carried out in beagle dogs as a reference control for a newly developed beta blocker. No significant drug-induced changes were detected in any animals by various ophthalmological examinations such as ERG, tear flow, lysozymal activity in tears, etc. However, an unusual pathological change was detected in the lacrymal gland of all five dogs treated with practolol and not in control animals. Macroscopically, the lacrymal glands assumed a blackish brown to deep black colour on both the outside and the cut surface. Microscopically, fine, dark-brown pigment granules were present in the apical and supra-nuclear portion of the cytoplasm of predominantly serosal type epithelial cells. These pigments reacted positively to Schmorl's method for lipofuscin, but gave a negative PAS reaction for polysaccharide, Prussian blue for iron and Ziehl-Neelsen method for ceroid pigment. They were detected as membrane-bound electron-dense bodies by electron microscopy. Similar pigments were also deposited in the cytoplasm of the apocrine sweat gland. Although the mechanism of the accumulation of these granules is far from clear, concentration of practolol in the lacrymal gland is considered to be very closely related to the presence of these granules. A possible mechanism for ocular toxicity by practolol, involving this change, is discussed.
authors.affiliation: Hamamatsu Seigiken Research Laboratory Co., Shizuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tsuchitani
authors.forename: I
authors.initials: I
authors.lastname: Narama
authors.forename: S
authors.initials: S
authors.lastname: Kohda
mesh_terms: D000818:Animals; D003594:Cytoplasmic Granules / Q000032:analysis / Q000648:ultrastructure*; D004285:Dogs; D004848:Epithelium / Q000187:drug effects / Q000648:ultrastructure; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D008854:Microscopy, Electron; D010860:Pigments, Biological / Q000032:analysis*; D011217:Practolol / Q000633:toxicity*; D013545:Sweat Glands / Q000187:drug effects / Q000648:ultrastructure; D013666:Tears / Q000378:metabolism
chemical_list: D010860:Pigments, Biological; D011217:Practolol