Impairment of lipoglycoprotein metabolism in rat liver cells induced by 1,2-dichloroethane

D. Cottalasso, G. Barisione, L. Fontana, C. Domenicotti, M. A. Pronzato, G. Nanni

Research output: Contribution to journalArticlepeer-review

Abstract

Background - 1,2-Dichloroethane (DCE) is a volatile liquid readily absorbed through dermal, digestive, or inhalatory routes. After inhalation or oral administration to rats, death occurs within a narrow range of concentrations (six hour LC50 = 5100 mg/m3). Exposure to single high doses of DCE resulted in adverse effects on the central nervous system, liver, kidneys, adrenals, and lungs. The liver showed fatty changes and hepatocellular necrosis with haemorrhage. These injuries are probably related to changes in several cell functions and constituents. Therefore, it was decided to investigate whether DCE was capable of impairing the secretion of hepatocellular lipoglycoproteins acting both at the level of the Golgii apparatus and endoplasmic reticulum. Methods - Isolated hepatocytes of Wistar rats were prelabelled with two precursors of lipoglycoproteins 3H-Na-palmitate and 14C-glucosamine, and then exposed to concentrations of DCE from mean (SD) 4.4 (0.03) to 6.5 (0.02) mM for different durations ranging from five to 60 minutes. To measure lipid and sugar bound radioactivity, a preliminary separation of cell homogenate, cytosol, total microsomes, (Golgi apparatus, and lipoglycoproteins secreted into cell suspension medium was carried out. Results - After five minutes of exposure, DCE did not induce obvious changes in cell viability or lactic dehydrogenase leakage, but a significant (p <0.01) depletion of reduced glutathione content was seen (40.10 (4.3) nM/106 cells). Furthermore, the cells poisoned by DCE started to show noticeable accumulation of 3H-Na-palmitate in the Golgi apparatus after five minutes (5103 (223) dpm/106 cells) and in the microsomes after 15 minutes (85 470 (7190) dpm/106 cells). There was a simultaneous significant increase in 14C-glucosamine content in the Golgi apparatus (690 (55) dpm/106 cells) and the microsomes (15 975 (2035) dpm/106 cells). The specific radioactivity of lipid and sugar moieties incorporated in secreted lipoglycoproteins was already significantly reduced after only five minutes of exposure (480 (57) dpm/106 cells for lipids, and 315 (45) dpm/106 cells for sugars). Conclusions - Overall, DCE, like other haloalkanes, produces a block of secretion of hepatocellular lipoglycoproteins as early as five minutes after poisoning. The simultaneous percentage increases into Golgi apparatus and microsomes of lipid and sugar bound radioactivity suggest that lipid retention at the sites of processing of lipoglycoproteins would probably play an important part in the early stages of cellular accumulation of fat after exposure to DCE.

Original languageEnglish
Pages (from-to)281-285
Number of pages5
JournalOccupational and Environmental Medicine
Volume51
Issue number4
Publication statusPublished - 1994

ASJC Scopus subject areas

  • Environmental Science(all)
  • Public Health, Environmental and Occupational Health

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