Prevention of toxin-induced cytoskeletal disruption and apoptotic liver cell death by the grapefruit flavonoid, naringin.
The protein phosphatase-inhibitory algal toxins, okadaic acid and microcystin-LR, induced overphosphorylation of keratin and disruption of the keratin cytoskeleton in freshly isolated rat hepatocytes. In hepatocyte cultures, the toxins elicited DNA fragmentation and apoptotic cell death within 24 h. All these toxin effects could be prevented by the grapefruit flavonoid, naringin. The cytoprotective effect of naringin was apparently limited to normal hepatocytes, since the toxin-induced apoptosis of hepatoma cells, rat or human, was not prevented by the flavonoid.
Department of Cell Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001427:Bacterial Toxins / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects*; D044950:Flavanones; D005419:Flavonoids / Q000494:pharmacology*; D005638:Fruit; D006801:Humans; D008099:Liver / Q000166:cytology; D008387:Marine Toxins; D052998:Microcystins; D019319:Okadaic Acid / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D000975:Antioxidants; D001427:Bacterial Toxins; D044950:Flavanones; D005419:Flavonoids; D008387:Marine Toxins; D052998:Microcystins; D010456:Peptides, Cyclic; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; C057862:cyanoginosin LR; C005274:naringin