Fundamental Toxicological Sciences

2019 - Vol. 6 No. 3

2019 - Vol. 6

Impairment of fertilization efficiency in mice following nano-sized titanium exposure Vol.6, No.3, p.113-116
Nobuhiko Miura , Katsumi Ohtani , Tatsuya Hasegawa , Gi-Wook Hwang , Hiroki Yoshioka
Released: May 14, 2019
Abstract Full Text PDF[914K]

Titanium dioxide nanoparticles (TiNP) are widely used commercially and exist in a broad range of applications and consumer products such as exterior wall paints, antibacterial agents, white pigments, and sunscreens. We previously reported that the testis is a fragile organ against titanium toxicity as compared to the liver; TiNP has been shown to decrease both the sperm motility and the sperm numbers, that is, TiNP quantitatively and qualitatively change the sperm functions. There are, however, few reports regarding to the influence of TiNP on fertility ability. In this paper, we evaluated the influence of TiNP on fertilization rate using in vitro fertility (IVF) assay. Male C57BL/6J mice were administered orally with TiNPs (10 mg/kg or 100 mg/kg). Mice were sacrificed 24 hr after the administration. As a result, TiNP (10 mg/kg group) significantly decreased the fertilization rate. In the higher dose group (100 mg/kg), the degree was weaker than in the lower dose group. Our results indicate that TiNP reduces not only the sperm motility but also the fertility, and it will be useful information in considering the influence of TiNP on next generation.

Magnoliae Cortex extract protects PC12 cells from cytotoxicity induced by hydrogen peroxide or 6-hydroxydopamine through enzyme induction Vol.6, No.3, p.107-112
Takahito Nishiyama , Yasuhiro Masuda , Tadashi Izawa , Tomokazu Ohnuma , Kenichiro Ogura , Akira Hiratsuka
Released: April 24, 2019
Abstract Full Text PDF[1M]

Alzheimer’s and Parkinson’s disease are neurodegenerative disorders of unknown cause for which there is no cure or way of preventing or slowing its progression. Various genetic and environmental factors are thought to be involved in the onset of neurodegenerative diseases. Oxidative stress, such as the generation of reactive oxygen species and lipid peroxidation, is a major factor in initiating the disease process. However, oxidative stress in cells is known to be suppressed by drug-metabolizing enzymes, such as NAD(P)H:quinone oxidoreductase 1 (NQO1), and antioxidant enzymes, such as catalase. Here, we used PC12 cells, which are a recognized model for neuronal cell death and neurite extension, to investigate whether Magnoliae Cortex derived from the Magnoliaceae plant family can induce these enzyme activities. Our results reveal that Magnoliae Cortex extract induces the activity of both NQO1 and catalase. In addition, the cytotoxic effect of hydrogen peroxide and 6-hydroxydopamine was significantly suppressed by pretreatment of the cells with Magnoliae Cortex extract. Based on our findings, we conclude that induction of these enzyme activities by Magnoliae Cortex extract leads to an enhancement of its cytoprotective effect.

Original Article
Genotoxicity and subchronic toxicity studies of Taiwanofungus camphoratus extract Vol.6, No.3, p.81-106
Jian-Yu Lin , Mei-Chun Chen , Emerson Chiu
Released: April 05, 2019
Abstract Full Text PDF[2M]

Taiwanofungus camphoratus is an edible and medicinal mushroom originating in Taiwan. Several researches have revealed T. camphoratus possessed various biological activities, including anti-cancer, immunomodulation, liver protection and anti-inflammation. Recently, it has been widely used in food supplements and drug development for its health benefits and medicinal properties. Therefore, the safety issue is the primary concern for consumers. The aim of this study was to evaluate the toxicological effects of T. camphoratus extract that was composed of extracts from cut-log cultivated fruiting body and solid-state culture of T. camphoratus. The genotoxicity tests, rodent and non-rodent repeated dose toxicity studies were performed. The results of the genetic toxicology tests including in vitro bacterial reverse mutation assay, in vitro chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay were all negative that indicated neither mutagenicity nor clastogenicity was caused by T. camphoratus extract. Moreover, 13-week and 26-week repeated dose oral toxicity studies in rats showed that no significant adverse effects of T. camphoratus extract were found up to dosages of 3400 mg/kg and 1700 mg/kg for male and female rats, respectively. The results of 28-day repeated dose oral toxicity study in beagle dogs showed no-observed-adverse-effect-level (NOAEL) of T. camphoratus extract up to dosage of 1500 mg/kg for male and female dogs. Accordingly, these results provided the safety information of T. camphoratus extract that supported for using in food supplements or medicinal usage.

Original Article
Age-dependent aggravation of oral malodor and periodontal disease in dogs Vol.6, No.3, p.75-79
Naoki Iwashita , Kazutoshi Sugita , Sayaka Murata , Keiko Ichimura , Mitsuyuki Shirai , Masaharu Hisasue , Miyoko Saito , Takuma Aoki , Yukihiko Takagi , Fumitoshi Asai
Released: April 04, 2019
Abstract Full Text PDF[743K]

Halitosis or oral malodor is correlated with the concentration of volatile sulfur compounds (VSCs) produced in the oral cavity by metabolic activity of periodontal pathogenic germs. Our previous study demonstrated that VSCs in canine breath air can be measured using a portable VSC monitor. The aim of this study was to assess the association between oral malodor and periodontal disease in dogs. Forty-three laboratory Beagle dogs (1-16 years of age, 24 males, 19 females) were included in this study. Oral halitosis was evaluated by the organoleptic test score (OS) and by measuring the oral levels of VSCs: hydrogen sulfide (H2S; HS), methyl mercaptan (CH3SH; MM), and dimethyl sulfide (CH3SCH3; DMS) using OralChroma™. The calculus index (CI) and the gingival index (GI) were measured as periodontal parameters. Oral levels of halitosis parameters (OS, HS, MM, CI, and GI) in Group 2 dogs (7-16 years of age) were significantly higher than those in Group 1 dogs (1-6 years of age). In addition, significant positive relationships were found between oral malodor and periodontal disease, both of which are age-dependent in dogs. The present study suggested that aging is an important factor for oral malodor and periodontal disease in dogs.

Original Article
Twenty-eight-day oral toxicity study of L-hydroxyproline in rats with 14-day post-treatment observation period Vol.6, No.3, p.65-74
Saori Akiduki , Yoko Kawada , Fumiko Watanabe , Toshikazu Kamiya , Koji Morishita
Released: April 04, 2019
Abstract Full Text PDF[1M]

Repeated-dose oral toxicity of L-hydroxyproline (Hyp) was assessed in male and female SD rats by gavage for 28 days at dose level of 40, 200, 1,000 or 4,000 mg/kg/day. The reversibility of treatment-related changes was also examined by providing 14-day recovery period in the control group and 4,000 mg/kg group. In the results, reduced body weight gain with decreased food consumption was noted in males at 4,000 mg/kg/day. The histopathological evaluation revealed increased incidences of focal dilatation of the renal tubules with narrowing of the tubular cell liner and focal interstitial fibroplasia in the kidney of males at 1,000 and 4,000 mg/kg and females at 4,000 mg/kg. The lack of kidney specific serum chemical or urinalysis findings supported that the renal changes were very mild. Based on the above results, it was concluded that the no observed adverse effect level (NOAEL) of Hyp was 200 mg/kg/day.