Benzodiazepines are widely used psychoactive drugs, and have been detected in several clinical cases of accidental exposure and suicide. It was reported that benzodiazepine concentration was changed in post-mortem blood. However, there is no concrete evidence to reasonably explain why benzodiazepine concentration in post-mortem blood cannot be accurately determined. In this study, we showed that the concentrations of almost all types of benzodiazepines examined were significantly decreased in the presence of hemoglobin (Hb) in vitro. In particular, bromazepam was hardly recovered in its intact form. We detected bromazepam metabolites with Hb by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). The mass spectra showed that bromazepam was metabolized into 3-hydroxybromazepam. Our results suggest that 3-hydroxybromazepam was formed via the Fenton reaction with the divalent iron ion in Hb. Furthermore, 3-hydroxybromazepam was also detected in post-mortem blood of autopsied subjects who intentionally ingested bromazepam, and its concentration increased with time after death. These results suggest that 3-hydroxybromazepam is a potential biomarker of bromazepam poisoning to estimate the amount of bromazepam ingested.

Flavones are belonging to flavonoids group and show diverse biological functions. Therefore, they have much attention as drugs for maintaining human health via contributing prevention and treatment of various diseases like cancers, diabetes, neurodegenerative diseases, ischemic stroke, inflammation diseases and cardiovascular diseases. On the other hand, human monoblastic leukemia U937 cells have been used as an excellent in vitro model system for macrophage development induced in response to various reagents such as all-trans retinoic acid (RA). Here, we investigated the effects of flavones (flavone and its hydroxy derivatives) on the RA-induced O₂^--generating activity of U937 cells. Very interestingly, at a concentration of 20 μM, 3’, 4’-dihydroxyflavone caused up-regulation of the RA-induced O₂^--generating activity (to ~ 170%) although flavone and other hydroxyflavone derivatives tested showed remarkable inhibitory effects on the RA-induced O₂^--generating activity. The promoting effects of 3’, 4’-dihydroxyflavone on the RA-induced O₂^--generating activity showed the maximum value at a concentration of 10 μM. Semiquantitative RT-PCR and immunoblotting revealed that 10 μM 3’, 4’-dihydroxyflavone up-regulates the RA-induced O₂^--generating activity via enhancing gene expression of gp91-phox (mRNA level: to ~ 160%, protein level: to ~ 200%) while 10 μM 5, 7-dihydroxyflavone and 10 μM 3’, 4’, 5, 7-tetrahydroxyflavone down-regulate the RA-induced O₂^--generating activity via inhibiting gene expression of gp91-phox and p47-phox. These findings also showed that there may be various risks involved in use of phytochemical mixtures.

This study reported acrylamide, a carcinogenic substance produced by the Maillard reaction, in dog food, as a part of understand the mechanism of canine carcinogenesis. These results indicated that the average concentrations of acrylamide in dry, retort, and canned dog food were 39.6, 11.0, and 10.7 ng/g, respectively. Among the three, dry dog food exhibited significantly higher concentration. The daily intake of acrylamide by dogs was calculated to be 590 ng/kg/day, which is approximately four times higher than that of humans.

Monascus Color Y-001, a natural food dye produced from Monascus purpureus fermentation, was administered orally by gavage to male and female SD rats for 90 days at doses of 0 (vehicle: 0.1% Tween 80, 10 mL/kg bw), 100, 300 and 1000 mg/kg/day. During the treatment period, there was no death, and test article effects on clinical signs were limited to reddish feces, soiled perineal region (reddish color) and salivation that were observed in both sexes at 300/1000 mg/kg/day. Prolongation in PT and APTT occurred in males at 1000 mg/kg/day, and the changes were without any evidence suggesting hemorrhage and/or hepatic dysfunction. Treatment-related histopathological findings were noted in thymus, liver and kidney, and were limited to the females at 1000 mg/kg/day. These findings included decreased cellularity in thymus with decreased thymus weights attributed to nonspecific stress, centrilobular hepatocellular hypertrophy with increase of liver weights attributed to adaptive change, and vacuolation of proximal tubules in kidneys accompanied with related parameter changes in urinalysis. From these results, the no-observed-adverse-effect level (NOAEL) was judged to be 300 mg/kg/day both in male and female rats.

Heavy metals are ubiquitous in the environment and nature, and even in trace amounts, chronic exposure to them can have negative health effects on humans. It is known that rice, in particular, easily accumulate cadmium (Cd). Cd can accumulate in the human body and affect human health. In Japan, rice is a staple food and a main leading source of Cd poisoning. The Tokyo Metropolitan Government has been investigating the Cd content in brown rice sold in Tokyo since 1973 in order to prevent Cd poisoning in humans. A survey result from 2010 to 2018 stated that there was no sample that exceeded the maximum limit (0.4 ppm). Moreover, compared with past survey reports in Tokyo, the Cd content in brown rice has obviously decreased. In this survey, cadmium intake from brown rice was not particularly problematic in terms of food hygiene.