Fundamental Toxicological Sciences

2018 - Vol. 5 No. 5

2018 - Vol. 5

Original Article
Effects of fish oil-enriched Sasa-kamaboko diet in decreasing hepatic lipid levels in a mouse fatty liver disease model Vol.5, No.5, p.171-179
Masaaki Miyata , Tomoki Kinoshita , Kaho Miyahara , Mizuki Sato , Asaka Arikawa , Yoshimasa Sugiura , Yoshihisa Suzuki , Emiko Okazaki
Released: November 21, 2018
Abstract Full Text PDF[2M]

The influence of fish oil-enriched Sasa-kamaboko (a Japanese processed seafood) diet on lipid metabolism was investigated using mice lacking farnesoid X receptor (FXR) as a fatty liver disease model. Sasa-kamaboko (SK) was made from Alaska pollock surimi (fish paste), enriched with fish oil (0%, 2.5%, or 5.0%) and then freeze-dried. Fxr-null mice were fed the dried SK, mixed with AIN-93M chow in the ratio 1:1 (50% SK diet) or 1:3 (25% SK diet), for 4 weeks. Hepatic triglyceride levels, and total cholesterol levels were significantly decreased, which were dependent on the amount of added fish oil in 25% and 50% SK diets. Hepatic fatty acid synthase (Fas), acetyl-CoA carboxylase 1 (Acc1), and stearoyl CoA desaturase 1 (Scd1) mRNA levels and Fas protein levels were decreased in groups fed fish oil-enriched 50% SK diets. Brain and serum non-esterified fatty acid levels were significantly decreased in the groups fed fish oil-enriched 50% SK diet, whereas brain and serum, (but not hepatic) phospholipid levels were significantly increased in the groups. Hepatic, serum and brain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; 22:6 n-3), and eicosapentaenoic acid (EPA; 20:5 n-3) levels (except for brain EPA levels) were significantly increased in groups fed fish oil-enriched 50% SK diet, whereas hepatic and serum mono-unsaturated fatty acid, oleic acid (18:1 n-9), and palmitoleic acid (16:1 n-7) levels were significantly decreased in the groups. These results suggest that a diet containing fish oil-enriched SK enhances hepatic lipid-lowering through the alteration of hepatic fatty acid composition in a fatty liver disease mouse model.

Original Article
Derivation of acceptable daily exposure value for alanine, N,N-bis(carboxymethyl)-, trisodium salt Vol.5, No.5, p.167-170
Masayuki Mishima , Dana Hoffmann , Gaku Ichihara , Satoshi Kitajima , Makoto Shibutani , Satoshi Furukawa , Akihiko Hirose
Released: November 06, 2018
Abstract Full Text PDF[794K]

Use of a non-phosphate detergent builder, alanine, N,N-bis(carboxymethyl)-trisodium salt (ABCT), has been expanded to wide range of washing and cleaning products for consumer uses and industrial applications including cleaning agents in food or pharmaceutical factories. Therefore, determination of acceptable daily exposure (ADE) of ABCT by oral, parenteral or inhalation route based on updated toxicity database could provide valuable information on the risk management for protection of consumers, patients and workers. Here, we proposed the ADEs based on the toxicological information of various in vivo and in vitro non-human studies. Because the full report of each toxicity study was not disclosed, derivation of the ADE was done based on available information mainly from ECHA database. ABCT exhibited renal toxicity as a main effect; however, ABCT did not exhibit carcinogenicity, genotoxicity, reproductive toxicity, irritation, and sensitization. Applying modification factors to the NOAEL of the animal study of longest treatment period, oral ADE was determined as 260 mg/person/day. Taking the oral bioavailability into the consideration of conversion to other routes, parenteral and inhalation ADEs were determined as 50 mg/person/day.

Protection from acetaminophen-induced hepatotoxicity by post-administration of 1O, 20O-diacetyl kamebakaurin in mice Vol.5, No.5, p.161-165
Hiroki Yoshioka , Hiroyuki Ohnishi , Masae Yoshikawa , Ming-Yu Gui , Yong-Ri Jin , Xu-Wen Li , Yoshiyuki Adachi , Naohito Ohno , Koichi Takeya , Yukio Hitotsuyanagi , Nobuhiko Miura , Yutaka Aoyagi
Released: October 19, 2018
Abstract Full Text PDF[3M]

Our previous study demonstrated that pre-administration of 1O, 20O-diacetyl kamebakaurin (Ac2KA) protected against acetaminophen (APAP)-induced hepatotoxicity. In the current study, we aimed to investigate whether post-administration of Ac2KA also protects against APAP-induced hepatotoxicity. Eight-week-old male C57BL/6J mice were fasted and then intraperitoneally injected with 450 mg/kg APAP or saline. At 60-min after the APAP injection, Ac2KA (50 mg/kg) or an ethanol/olive oil emulsion was orally administered. At 16-hr after the injection, the mice were killed, and blood samples were collected for plasma analysis. As a positive control, we used N-acetylcysteine (200 mg/kg, i.p.). Posttreatment with Ac2KA significantly attenuated APAP-induced plasma alanine aminotransferase and aspartate aminotransferase levels. Ac2KA administration also decreased the APAP-induced hepatic malondialdehyde concentration. Moreover, histological evaluation supported these observations. Our results show that Ac2KA exerts protective effects against APAP-induced hepatotoxicity when administered as both pretreatment and post-treatment.