Fujiko Hirasawa

Rotavirus double-stranded RNA induces apoptosis and diminishes wound repair in rat intestinal epithelial cells

Background:  Recent studies have shown that toll‐like receptor 3 (TLR3) recognizes double‐stranded RNA (dsRNA). Rotaviruses, having a dsRNA genome, infect intestinal epithelial cells (IEC) and cause acute gastroenteritis in young children. The aim of the present study was to clarify the pathophysiological function of rotavirus dsRNA in IEC.

Styrene monomer primarily induces CYP2B1 mRNA in rat liver

To determine the cytochrome P450 (CYP) primarily expressed after styrene exposure, seven forms of hepatic CYP mRNA in rats treated with 600 mg kg−1 styrene were examined. CYP1A2, CYP2B1/2, CYP2E1 and CYP3A2 mRNA were observed using real-time LightCycler PCR. The amount of CYP2B1 mRNA was significantly increased, 47-fold compared with controls, suggesting that this CYP is the primary cytochrome P450 in rats exposed to styrene. Significant increases in the amount of CYP2E1, CYP1A2 and CYP2B2 mRNA were also observed after styrene exposure, and their increase levels were 3.1-, 1.7- and 1.7-fold higher than controls, respectively. Western blot analysis also indicated that the protein levels of CYP2B1, CYP2B2, CYP2E1 and CYP1A2 showed clear increases after styrene treatment, corresponding to their mRNA expression. CYP2C11 mRNA decreased significantly in rats after styrene exposure. CYP1A1 was detected at the mRNA level in rat liver, but it was not detected at the protein level. The expression of epoxide hydrolase (EH), involved in Phase I drug metabolism, was also examined. EH mRNA increased 2-fold compared with controls after styrene exposure. Styrene thus appears to be a chemical compound that induces multiple CYPs. The results demonstrate that CYP2B1 is the primarily induced CYP form by styrene treatment to rats at acute toxic level.

The effect of silver administration on the biosynthesis and the molecular properties of rat ceruloplasmin

To examine the cause of the altered ceruloplasmin (Cp) metabolism by silver administration, we analysed the properties of serum Cp by gel filtration chromatography, affinity chromatography and polyacrylamide gel electrophoresis. Metal contents in the Cp fraction from the silver-treated group were estimated as approximately 0.8 atom of silver and 4.2 atoms of copper per molecule, and as 5.9 atoms of copper for the control group. These findings confirm that holo-Cp from rat serum administered with silver nitrate exists as a silver-bound inactive form, suggesting that silver displaces one of Cps copper atoms associating with oxidase activity. Matured holo-Cp also appeared in the Golgi in both groups, however, the amounts of enzymatically active holo-Cp showed a decrease after silver administration, while the apo-Cp level was hardly changed. These findings suggest that silver-bound holo-Cp is accomplished at Golgi.

Distribution and accumulation of [2,3-14C]acrylonitrile in rat after single injection☆

The distribution and accumulation of acrylonitrile after the single i.p. injection of [2,3-14C]acrylonitrile were examined by whole-body autoradiography and by the determination of 14C radioactivities in several tissues and subcellular fractions after a whole-body perfusion. 14C Radioactivity was seen strongly in blood, particularly in red blood cells, and in several tissues including lung, liver, and kidney. Longer retention of radioactivity in brain and muscle was observed. At the subcellular level a relatively high specific radioactivity was seen in cytosol fractions of the brain, liver, and kidney.