In vivo and in vitro reversibility of chlorphentermine-induced phospholipidosis in rat alveolar macrophages.
Chlorphentermine (CP) is a cationic, amphiphilic drug (CAD) that has been studied widely for its ability to induce phospholipidosis, a disorder characterized by excessive accumulation of cellular phospholipid and ultrastructural development of lysosomal lamellar bodies (LLBs) in the cell. The accumulation of inducing drug correlates with increasing phospholipids. In the present study, we examined the reversibility of this disorder in rat alveolar macrophages (AMs) following a 7-day treatment (30 mg/kg/day, ip). The reversibility of phospholipidosis was examined under in vivo conditions and under in vitro conditions in cell cultures for a period of up to 12 days. There was a marked reduction in cellular CP levels and phospholipid content after 4 days of recovery, both in vivo and in vitro; however, there was no indication of significant loss of LLBs. Beyond this time point, ultrastructural recovery from phospholipidosis lagged behind the biochemical recovery temporally and was somewhat less rapid in vitro than in vivo. By 12 days of recovery, AMs from both groups had recovered biochemically, but a moderate level of LLBs was still present in some AMs in the in vitro recovery group. The results of this study indicate that there are more similarities than differences when comparing the recovery of phospholipidotic cells in vitro to that occurring in vivo. We conclude that the use of cell cultures may prove valuable in studying the reversibility of CAD-induced phospholipidosis.
McCloud
C M
CM
Department of Pharmacology and Toxicology, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown, USA.
Beard
T L
TL
Kacew
S
S
Reasor
M J
MJ
D000818:Animals; D002478:Cells, Cultured; D002745:Chlorphentermine / Q000032:analysis / Q000633:toxicity*; D008064:Lipidoses / Q000139:chemically induced / Q000473:pathology*; D008247:Lysosomes / Q000187:drug effects / Q000473:pathology; D016676:Macrophages, Alveolar / Q000737:chemistry* / Q000648:ultrastructure; D008297:Male; D010743:Phospholipids / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010743:Phospholipids; D002745:Chlorphentermine