title: Neutral sphingomyelinase-induced ceramide accumulation by oxidative stress during carbon tetrachloride intoxication.
abstract: Ceramide is a biologically active lipid causing apoptosis in a variety of cells. In this study, we examined the effect of CCl4 on the ceramide metabolism and indicators of oxidative stress. After 12 h of oral administration of CCl4 (4 ml/kg body weight as a 1:1 mixture of CCl4 and mineral oil) to rats, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were increased. Antioxidants such as vitamins C and E were decreased in the liver and kidney. In addition, the ratio of GSH/GSSG in the liver, plasma, kidney, and brain decreased at 2h. The total ceramide in the liver significantly increased as early as 2h after CCl4 administration. After 24 and 36 h, the total ceramide in plasma and the kidney was also augmented. In the brain, the total ceramide dramatically increased at 36 h. These results suggested that the increased ceramide in plasma was transferred to the kidney and the brain. The activity of neutral sphingomyelinase (SMase), which was reported to be enhanced by the decrease of GSH, was significantly increased after CCl4 treatment in the liver, kidney, and brain. However, acid SMase activities were not increased in the liver and kidney. Thus, the activation of neutral SMase via oxidative stress induced the increase of ceramide during CCl4 intoxication in not only the liver but also other tissues. These results suggested that the excess accumulation of ceramide causes damage in other organs including the kidney and brain during fulminant hepatic failure.
authors.affiliation: Department of Food Science and Nutrition, Nara Women's University, Nara 630-8506, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Ichi
authors.forename: Chiaki
authors.initials: C
authors.lastname: Kamikawa
authors.forename: Tomoka
authors.initials: T
authors.lastname: Nakagawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Ryoko
authors.initials: R
authors.lastname: Kataoka
authors.forename: Eri
authors.initials: E
authors.lastname: Nagata
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Chihiro
authors.initials: C
authors.lastname: Nakazaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Matsura
authors.forename: Shosuke
authors.initials: S
authors.lastname: Kojo
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D001921:Brain / Q000201:enzymology*; D002251:Carbon Tetrachloride; D002518:Ceramides / Q000378:metabolism*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014810:Vitamin E / Q000378:metabolism
chemical_list: D002518:Ceramides; D014810:Vitamin E; D002251:Carbon Tetrachloride; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D013108:Sphingomyelin Phosphodiesterase; D005978:Glutathione; D001205:Ascorbic Acid; D019803:Glutathione Disulfide