cyanoginosin-lr and naringin

Microcystin-LR, which is an inhibitor of serine/threonine protein phosphatase (PP)1 and PP2A, induces liver injury by its selective uptake system into the hepatocyte. It is also thought that microcystin-LR induces reactive oxygen species (ROS). We tried to establish the chemical prevention of microcystin-LR poisoning. We investigated the effect of grapefruit flavanone glycoside naringin on cytotoxicity of microcystin-LR using human hepatocyte uptake transporter OATP1B3-expressing HEK293-OATP1B3 cells. We found cytotoxicity of microcystin-LR was attenuated by naringin in a dose dependent manner. The inhibition magnitude of total cellular serine/threonine protein phosphatase activity induced by microcystin-LR was suppressed by naringin. In addition, uptake of microcystin-LR into HEK293-OATP1B3 cells was inhibited by naringin. Furthermore, microcystin-LR induced phosphorylation of p53 was inhibited by naringin. Regardless of the difference in the exposure pattern of pre-processing and post-processing of naringin, the toxicity of microcystin-LR was comparable. These results suggested that naringin is promising remedy as well as preventive medicine for liver damage with microcystin-LR. In addition, involvement of ROS production after exposure to the sublethal concentrations of microcystin-LR in the onset of cytotoxicity was negligible. Therefore, inhibition of microcystin-LR uptake and the pathway other than ROS production would be involved in the effect of naringin on the attenuation of microcystin-LR toxicity.

Topics: Cell Survival; Flavanones; HEK293 Cells; Humans; Hydrogen Peroxide; Liver-Specific Organic Anion Transporter 1; Marine Toxins; Microcystins; Organic Anion Transporters; Organic Anion Transporters, Sodium-Independent; Reactive Oxygen Species; Solute Carrier Organic Anion Transporter Family Member 1B3; Tumor Suppressor Protein p53

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.

Topics: Animals; Antioxidants; Apoptosis; Bacterial Toxins; Cell Death; Cells, Cultured; Cytoskeleton; Flavanones; Flavonoids; Fruit; Humans; Liver; Marine Toxins; Microcystins; Okadaic Acid; Peptides, Cyclic; Phosphoprotein Phosphatases; Rats; Rats, Wistar; Tumor Cells, Cultured