Okadaic acid is taken-up into the cells mediated by human hepatocytes transporter OATP1B3.

Okadaic acid is known as a diarrheal shellfish poison. It is thought that there is no specific target organ for okadaic acid after it has been absorbed into the body. However, the details of its pharmacokinetics are still unknown. In this study, we demonstrated that okadaic acid was more toxic to the hepatocyte-specific uptake transporter OATP1B1- or OATP1B3-expressing cells than control vector-transfected cells. In addition, PP2A activity, which is a target molecule of okadaic acid, was more potently inhibited by okadaic acid in OATP1B1- or OATP1B3-expressing cells compared with control vector-transfected cells. The cytotoxicity of okadaic acid in OATP1B1- or OATP1B3-expressing cells was attenuated by known substrates of OATP1B1- and OATP1B3, but not in control vector-transfected cells. Furthermore, after uptake inhibition study using OATP1B3-expressing cells, Dixon plot showed that okadaic acid inhibited the uptake of hepatotoxin microcystin-LR, which is a substrate for OATP1B1 and OATP1B3, in a competitive manner. These results strongly suggested that okadaic acid is a substrate for OATP1B3 and probably for OATP1B1, and could be involved in unknown caused liver failure and liver cancer. Since okadaic acid possesses cytotoxicity and cell proliferative activity by virtue of its known phosphatase inhibition activity.

Naringin attenuates the cytotoxicity of hepatotoxin microcystin-LR by the curious mechanisms to OATP1B1- and OATP1B3-expressing cells.

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.

Modulating the immobilization process of Au nanoparticles on TiO2(110) by electrostatic interaction between the surface and ionic liquids.

We found that the adsorption states of Au nanoparticles (NPs) on TiO(2)(110) varied with the ionic liquids (ILs) that encapsulate the NPs during the entire process from synthesis of NPs to immobilization of the NPs on the surface at 323 K. Five kinds of ILs, including three 1-butyl-3-methylimidazolium ([C(4)MIm]) cation-based ILs of tetrafluoroborate ([C(4)MIm][BF(4)]), hexafluorophosphate ([C(4)MIm][PF(6)]) and bis(trifluoromethylsulfonyl)amide ([C(4)MIm][NTf(2)]), and two [BF(4)] anion-based ILs of 1-(methoxymethyl)-1-methylpyrrolidinium ([PY1,1O1][BF(4)]) and N,N-diethyl-N-methyl-N-(2-methoxyethyl) ammonium ([N122,1O2][BF(4)]), were used. They provided different adsorption states of the Au NPs on the surface. We considered the determinant factor for the adsorption states of NPs on the surface from the viewpoint of electrostatic interactions between IL and IL and between IL and the surface. We deduced the influence of these interactions from the increments of NP's diameter and the amount of NPs after the immobilization, and obtained the order of anions as [BF(4)] ≈ [NTf(2)] > [PF(6)] for the three [C(4)MIm] based ILs and the order of cations as [PY1,1O1] > [C(4)MIm] > [N122,1O2] for the three [BF(4)] based ILs. Interestingly, the above orders were no match with the conventional physicochemical and chemical parameters but ß of Kamlet-Taft solvent descriptors and Lewis basicity of anions in the case of anions of ILs. The results of anions indicate that the chemical natures of ILs might affect the immobilization of NPs through hydrogen bonding or coordination bonding with the surface. We suggested that such a trend in anions was 'local viscosity' of ILs in the vicinity of surface. Besides, layer formation of IL on the surface might be also an influential factor to control the size of NPs and the surface density of NPs. Our results show that the combination of a charged surface and charged molecules has the potential for controlling locations of the NPs on the surface preferentially with tuning the electrostatic interaction.

Size control and immobilization of gold nanoparticles stabilized in an ionic liquid on glass substrates for plasmonic applications.

Gold (Au) nanoparticles were prepared by sputter deposition of Au metal in an ionic liquid (IL) of 1-butyl-3-methylimidazolium hexafluorophosphate (BMI-PF6). The size of Au nanoparticles was increased from 2.6 to 4.8 nm by heat treatment at 373 K. The nanoparticles uniformly dispersed in the IL were densely immobilized on a glass substrate surface modified with a silane coupling agent having an imidazole functional group by spreading the Au particle IL solution on the substrates, followed by heat treatment at 373 K. The optical property of the thus-obtained films was tunable by controlling the size of Au nanoparticles in the IL and the degree of immobilization. An intense localized surface plasmon resonance (LSPR) peak was observed in each Au particle film, and the wavelength of the LSPR peak could be controlled by changing the size of nanoparticles in the IL solution before immobilization. Photoexcitation of the LSPR peak caused enhancement of the photoluminescence of CdTe nanoparticles immobilized on Au nanoparticle films, probably due to the locally enhanced electric field formed around Au nanoparticles.