Toxic Effects of Trastuzumab (Herceptin) Combined with Doxorubicin in Chick Embryos

Yuji Yoshiyama1, Takashi Sugiyama2 and Motoko Kanke1
1 Kyoritsu College of Pharmacy, 2 Kitasato University(pp. 40-44)

Correspondence: Yuji Yoshiyama, Ph.D.
Division of Clinical Pharmacy, Kyoritsu College of Pharmacy
1-5-30, Shibakoen, Minato-ku, Tokyo 105-8512, Japan
Tel 03-5400-2667, Fax 03-5400-2667, E-mail:yoshiyama-yj@kyoritsu-ph.ac.jp

Original paper :AATEX 9(2-3):40-44
Abstract
The toxic activity of trastuzumab combined with doxorubicin was studied in chick embryos. Fertilized eggs of White Leghorns were incubated and used for experiment. Trastuzumab was injected with and without doxorubicin into the air sac of fertilized eggs. Electrocardiograms were recorded 0 to 60 min after the injection. After injection of each drug alone, the heart rate was not different compared with non-injected control. However, the heart rate was significantly decreased by injection with a combination of trastuzumab with doxorubicin. In addition, arrhythmia was produced by injection of both trastuzumab and doxorubicin. These findings indicate that the combination of trastuzumab with doxorubicin has a marked influence on the heart rate in chick embryos.

Key words: toxic interaction, trastuzumab, doxorubicin, chick embryo, electrocardiogram

The Effects of Dental Monomers on Total Nitrate/Nitrite Production in HEp-2 Cells

Koichi Imai, Yoshihisa Kosada, Syuhei Kuroda and Masaaki Nakamura
Osaka Dental University(pp. 45-51)

Correpondence: Koichi Imai, Ph.D.
Department of Biomaterials, Osaka Dental University
8-1, Kuzuhahanazono-cho, Hirakara-city, Osaka573-1121, Japan
Tel:072(864)3056, Fax:072(864)3156, E-mail:imai@cc.osaka-dent.ac.jp

Original paper :AATEX 9(2-3):45-51
Abstract
We determined the amount of total nitrate/nitrite produced from HEp-2 cells when cultured with various methacrylate monomers used for dental composite resins, such as Bis-GMA, Bis-MPEPP, UDMA, TEGDMA, EGDMA, and HEMA. For every monomer the total nitrate/nitrite level tended to decrease as the monomer concentration increased and no nitrate/nitrite production was observed at the monomer concentration of 500ƒÊg/mL and 250ƒÊg/mL. The monomer concentrations that inhibit nitrate/nitrite production to 50% of the control level (IC50) were in the following order: HEMA > EGDMA >> Bis-GMA † TEGDMA> Bis-MPEPP = UDMA. The cytotoxicities of monomers by the MTT method were also determined in terms of other IC50 values. There seems to be a correlation between the two IC50 values though the correlation coefficient was not high (R2=0.822). Further studies are necessary to elucidate the biological meaning of the effects of dental monomers on nitrate/nitrite production in vitro and those for in vivo toxicity mechanisms.

Key words: nitrate/nitrite, cytotoxicity, Bis-GMA, UDMA

Annual Meeting Report: The 16th Annual Meeting of the Japanese Society for Alternatives to Animal Experiments

(pp. 52 – 75)