1,2-Dichloropropane (DCP) toxicity is correlated with DCP-induced glutathione (GSH) depletion and is modulated by factors affecting intracellular GSH.
Acute 1,2-dichloropropane (DCP) poisoning in humans is relatively frequent in Italy, where DCP is widely diffused as a constituent of commercial solvents and dry cleaners. In this study we have investigated the effects of DCP on intracellular glutathione (GSH) content in main target tissues of male Wistar rats, i.e. liver, kidney and blood, in order to establish if a correlation between DCP-induced GSH depletion and tissue damage exists. Administration of DCP (2 ml/kg body weight orally) caused a dramatic loss of tissue GSH occurring 24 h after DCP intoxication, followed by a slow restoration approaching physiological levels after 96 h. GSH depletion was associated with a marked increase in serum GOT, GPT, 5'-nucleotidase, gamma-glutamyl transpeptidase, alkaline phosphatase, urea and creatinine, and a significant degree of hemolysis. When animals were pretreated with a GSH depleting agent, buthionine-sulfoximine (BSO) (0.5 g/kg body weight) i.p. 4 h before DCP intoxication, an increase of overall mortality was found, significantly different from the group of animals treated with DCP alone. On the contrary, the administration of a GSH precursor, N-acetylcysteine (NAC) i.p. (250 mg/kg body weight) 2 and 16 h after DCCP intoxication prevented the dramatic loss of cellular GSH and reduced the extent of injury in target tissues, as demonstrated by laboratory indices. Furthermore, statistical analysis of the data revealed a correlation between: (1) depletion of liver GSH and increase in serum GOT, GPT, 5'-nucleotidase, (2) depletion of kidney GSH and increase in serum urea and creatinine and (3) depletion of blood GSH and the occurrence of hemolysis.(ABSTRACT TRUNCATED AT 250 WORDS)
Imberti
R
R
Servizio di Anestesia e Rianimazione II, IRCCS Policlinico S. Matteo, Italy.
Mapelli
A
A
Colombo
P
P
Richelmi
P
P
Bertè
F
F
Bellomo
G
G
D015720:5'-Nucleotidase / Q000097:blood; D000111:Acetylcysteine; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D019328:Buthionine Sulfoximine; D002851:Chromatography, High Pressure Liquid; D005978:Glutathione / Q000172:deficiency / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives; D011407:Propane / Q000031:analogs & derivatives* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000097:blood
D000963:Antimetabolites; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D015720:5'-Nucleotidase; D005978:Glutathione; C004765:propylene dichloride; D011407:Propane; D000111:Acetylcysteine