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Loss of skeletal muscle mass and function with age represents an important source of frailty and functional decline in the elderly. Antioxidants from botanical extracts have been shown to enhance the development, mass, and strength of skeletal muscle by influencing age-related cellular and molecular processes. Tannase-treated green tea extract contains high levels of the antioxidants (−)-epicatechin (EC) and gallic acid that may have therapeutic benefits for age-related muscle decline. The aim of this study was to investigate the effect of tannase-treated green tea extract on various muscle-related parameters, without concomitant exercise, in a single-center, randomized, double-blind, placebo-controlled study. Administration of tannase-treated green tea extract (600 mg/day) for 12 weeks significantly increased isokinetic flexor muscle and handgrip strength in the treatment group compared with those in the placebo (control) group. In addition, the control group showed a significant decrease in arm muscle mass after 12 weeks, whereas no significant change was observed in the treatment group. Blood serum levels of follistatin, myostatin, high-sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-8, insulin-like growth factor-1 (IGF-1), and cortisol were analyzed, and the decrease in myostatin resulting from the administration of tannase-treated green tea extract was found to be related to the change in muscle mass and strength. In summary, oral administration of tannase-treated green tea extract containing antioxidants without concomitant exercise can improve muscle mass and strength and may have therapeutic benefits in age-related muscle function decline.

Agitation associated with dementia is frequently reported clinically but has received little attention in preclinical models of dementia. The current study used a 7PA2 CM intracerebroventricular injection model of Alzheimer's disease (AD) to assess acute memory impairment, and a bilateral intrahippocampal (IH) injection model of AD (aggregated Aβ1-42 injections) and a bilateral IH injection model of dementia with Lewy bodies (aggregated NAC61-95 injections) to assess chronic memory impairment in the rat. An alternating-lever cyclic-ratio schedule of operant responding was used for data collection, where incorrect lever perseverations measured executive function (memory) and running response rates (RRR) measured behavioral output (agitation). The results indicate that bilateral IH injections of Aβ1-42 and bilateral IH injections of NAC61-95 decreased memory function and increased RRRs, whereas intracerebroventricular injections of 7PA2 CM decreased memory function but did not increase RRRs. These findings show that using the aggregated peptide IH injection models of dementia to induce chronic neurotoxicity, memory decline was accompanied by elevated behavioral output. This demonstrates that IH peptide injection models of dementia provide a preclinical screen for pharmacological interventions used in the treatment of increased behavioral output (agitation), which also establish detrimental side effects on memory.

Hark-Soo Park,1 Sung-Sup Shin,1 Eun Ho Meang,1 Jeong-sup Hong,1 Jong-Il Park,1 Su-Hyon Kim,1 Sang-Bum Koh,1 Seung-Young Lee,1 Dong-Hyouk Jang,1 Jong-Yun Lee,1 Yle-Shik Sun,1 Jin Seok Kang,2 Yu-Ri Kim,3 Meyoung-Kon Kim,3 Jayoung Jeong,4 Jong-Kwon Lee,4 Woo-Chan Son,5 Jae-Hak Park6 1General Toxicology Team, Korea Testing and Research Institute, Seoul, Korea; 2Department of Biomedical Laboratory Science, Namseoul University, Cheonan, Korea; 3Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, Korea; 4National Institute of Food and Drug Safety Evaluation, Seoul, Korea; 5Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea; 6Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea Purpose: The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(-)) NPs in Sprague Dawley rats for 90 days.Methods: The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs.Results: No rats died during the test period. However, ZnOSM20(-) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion: A ZnOSM20(-) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. Keywords: negative charge, oral toxicity study, rat, ZnO

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity