Influence of chronic ethanol consumption on toxic effects of 1,2-dichloroethane: glycolipoprotein retention and impairment of dolichol concentration in rat liver microsomes and Golgi apparatus.
Our previous investigations demonstrated that 1,2-dichloroethane (DCE) and chronic ethanol treatment separately are able to impair glycoprotein metabolism and secretion, and reduce dolichol concentration in liver membranes. The purpose of this study was to investigate whether chronic ethanol consumption can induce potentiation of rat liver damage due to DCE haloalkane used in several chemical processes and in agriculture. Rats were given 36% of their total energy as ethanol in the Lieber-DeCarli liquid diet for 8 weeks (CH group). The pair-fed control group received an isocaloric amount of dextrine-maltose (PF group). "In vitro" experiments: the DCE (6.5 mM) treatment of isolated hepatocytes from CH rats enhanced glycoprotein retention and further reduced glycoprotein secretion and 14C-glucosamine incorporation compared to the hepatocytes from CH or from PF and DCE treated rats. "In vivo" experiments: a marked decrease of dolichol concentration in microsomes (in which dolichyl phosphate is rate-limiting for the initial glycosylation of protein) and in Golgi membranes (in which total dolichol is very important for membrane permeability, fluidity and vesicle fusion) was observed in CH rats acutely treated with 628 mg/kg bw of DCE (CH+DCE) compared with CH or PF+DCE treated rats. These data suggest that chronic ethanol consumption increases DCE liver toxicity by affecting protein glycosylation processes and impairing glycolipoprotein secretion, with a concomitant retention at the level of the Golgi apparatus.
Cottalasso
Damiano
D
Department of Experimental Medicine, Section of General Pathology, University of Genoa, via L.B. Alberti 2, 16132 Genoa, Italy. patgen@unige.it
Domenicotti
Cinzia
C
Traverso
Nicola
N
Pronzato
Maria
M
Nanni
Giorgio
G
D000704:Analysis of Variance; D000818:Animals; D004286:Dolichols / Q000378:metabolism*; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D005025:Ethylene Dichlorides / Q000633:toxicity*; D005260:Female; D005944:Glucosamine / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006056:Golgi Apparatus / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D004286:Dolichols; D005025:Ethylene Dichlorides; D006023:Glycoproteins; D000431:Ethanol; C024565:ethylene dichloride; D005944:Glucosamine