Effects of flavonoids on sphingolipid turnover in the toxin-damaged liver and liver cells.
BACKGROUND
The ceramide generation is an early event in the apoptotic response to numerous stimuli including the oxidative stress and ceramide analogs mimic the stress effect and induce apoptosis. Flavonoids of German chamomile are reported to exhibit the hepatoprotective effect. Flavonoids affect sphingolipid metabolism and reduce the elevated ceramide level in the aged liver. In the present paper, the ceramide content and production in the CCl4- and ethanol-treated liver and hepatocytes as well as the correction of sphingolipid metabolism in the damaged liver using the mixture of German chamomile flavonoids (chamiloflan) or apigenin-7-glucoside (AP7Glu) have been investigated.


RESULTS
The experiments were performed in either the rat liver or hepatocytes of normal, CCl4- and ethanol-treated or flavonoid- and toxin plus flavonoid-treated animals. [14C]palmitic acid and [methyl-14C-phosphorylcholine]sphingomyelin were used to investigate the sphingolipid turnover. Addition of the CCl4 or ethanol to isolated hepatocyte suspensions caused loss of cell viability and increased the lactate dehydrogenase release from the cells into supernatant and ceramide level in the cells. CCl4 administration to the rats enlarged ceramide mass as well as neutral sphingomyelinase (SMase) activity and reduced ceramide degradation by the neutral ceramidase. Pretreatment of isolated hepatocytes with flavonoids abrogated the CCl4 effects on the cell membrane integrity and normalized the ceramide content. Flavonoid administration to the rats normalized the elevated ceramide content in the damaged liver via neutral SMase inhibition and ceramidase activation.


CONCLUSIONS
The data obtained have demonstrated that flavonoids affect sphingolipid metabolism in the CCl4- and ethanol-damaged liver and liver cells. Flavonoids normalized activities of key enzymes of sphingolipid turnover (neutral SMase and ceramidase) and ceramide contents in the damaged liver and liver cells, and stabilized the hepatocyte membranes.
Babenko
Nataliya A
NA
Department of Physiology of Ontogenesis, Institute of Biology, Kharkov Karazin National University, 4, Svobody pl., Kharkov, 61077, Ukraine. babenko@univer.kharkov.ua
Shakhova
Elena G
EG
D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002518:Ceramides / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D000431:Ethanol / Q000633:toxicity; D005419:Flavonoids / Q000494:pharmacology*; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013107:Sphingolipids / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
D002518:Ceramides; D005419:Flavonoids; D013107:Sphingolipids; D000431:Ethanol; D002251:Carbon Tetrachloride; D007770:L-Lactate Dehydrogenase; D013108:Sphingomyelin Phosphodiesterase